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Danek E, Kavnoudias H, McLean C, Gerstenmaier JF, Di Muzio B. Radiological Variability in Pancreatic Neuroendocrine Neoplasms: A 10-Year Single-Center Study on Atypical Presentations and Diagnostic Challenges. Biomedicines 2025; 13:496. [PMID: 40002909 PMCID: PMC11853254 DOI: 10.3390/biomedicines13020496] [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: 01/07/2025] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Pancreatic neuroendocrine neoplasms (PNENs) are rare but clinically significant tumors with variable radiological presentations that complicate diagnosis. While typical PNENs are well characterized, atypical features, such as cystic or hypoenhancing patterns, are less understood and can lead to diagnostic delays or misdiagnosis. This study aimed to evaluate atypical radiological presentations of PNENs, focusing on their impact on diagnostic pathways and differentiation from other pancreatic pathologies. Methods: A retrospective review was conducted of all PNEN cases diagnosed at a single tertiary center between 2010 and 2020. Cases with histopathological confirmation and available cross-sectional imaging were included. Radiological features were categorized as typical (solid and hyperenhancing) or atypical (cystic and hypoenhancing). Demographic, radiological, and pathological data were analyzed. Comparisons between typical and atypical PNENs were performed using descriptive and inferential statistics. Results: Among 77 PNEN cases, 39 met the inclusion criteria. Atypical radiological presentations were identified in 46% of cases, including cystic (18%) and hypoenhancing (28%) lesions. Hypoenhancing PNENs were significantly more likely to present with advanced disease (54% vs. 14% in typical PNENs, p = 0.016). In contrast, none of the cystic PNENs exhibited advanced disease. Atypical PNENs posed greater diagnostic challenges, with alternative diagnoses initially considered in 64% of hypoenhancing and 43% of cystic cases compared to 10% of typical PNENs (p = 0.0042). Conclusions: Atypical PNENs, particularly hypoenhancing lesions, present significant diagnostic challenges and are more likely to be associated with advanced disease. These findings highlight the need for improved recognition of atypical imaging patterns and more precise diagnostic strategies. However, the retrospective design and small cohort size limit the generalizability of our findings. Further multicenter studies are warranted to refine the imaging criteria and optimize the differentiation from other pancreatic neoplasms.
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Affiliation(s)
- Eleanor Danek
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Helen Kavnoudias
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Catriona McLean
- Department of Anatomical Pathology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Jan F. Gerstenmaier
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Bruno Di Muzio
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
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2
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Ankerstjerne MP, Giovannoni S, Christensen LG, Möller S, Holmager P, Knigge U, Ellebaek MB, Rathe M. Pediatric Neuroendocrine Tumors in Denmark: Incidence, Management, and Outcome From 1995 to 2020. Pediatr Blood Cancer 2025; 72:e31420. [PMID: 39579111 DOI: 10.1002/pbc.31420] [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: 08/03/2024] [Revised: 10/04/2024] [Accepted: 10/16/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND Neuroendocrine tumors (NETs), although rare, are considered one of the most common gastrointestinal and bronchopulmonary pediatric neoplasms. We aimed to determine the incidence, tumor characteristics, management, and outcome of NETs and explore the role of genetic predisposition, focusing on low and intermediate grade tumors. METHODS Using the Danish National Pathology Registry, we conducted a nationwide retrospective study including all Danish children aged ≤18 years diagnosed with a pathology-proven NET between 1995 and 2020. RESULTS We identified 220 patients, with a 1.89:1 female to male ratio. The yearly incidence was 6.84 per 1 million children, with no significant change in incidence throughout the observation period. NETs were located in the appendix (93.2%), the pulmonary system (4.5%), and pancreas (2.3%). One recurrence was noted in the pancreas in a genetically predisposed patient with multiple neuroendocrine neoplasia type 1 (MEN1), resulting in an overall recurrence rate of 0.5% (0% in appendiceal NETs; 0% in bronchopulmonary NETs; 20.0% in pancreatic NETs). No NET-related mortality was registered. Four patients had a known predisposing genetic condition, one appendiceal NET associated with neurofibromatosis type 1, and three pancreatic NETs associated with MEN1. Postsurgical surveillance regimes, choice of tumor markers, and imaging modality varied throughout the study period. CONCLUSIONS We confirmed a stable incidence of pediatric NETs during the study period. The overall recurrence rate was 0.5% and no NET-related mortality was observed. Known genetic predisposition was present in 1.8% of patients. Future guidelines should consider the apparent indolent nature and excellent prognosis of these tumors.
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Affiliation(s)
- Mona P Ankerstjerne
- Department of Pediatrics Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | - Sara Giovannoni
- Department of Surgery "Research Unit for Surgery", Odense University Hospital, Odense, Denmark
| | | | - Sören Möller
- Department of Clinical Research "Research Unit OPEN", University of Southern Denmark, Odense, Denmark
| | | | - Ulrich Knigge
- Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen, Denmark
- Advisory Board of the European Neuroendocrine Tumor Society, (ENETS), Berlin, Germany
| | - Mark B Ellebaek
- Department of Surgery "Research Unit for Surgery", Odense University Hospital, Odense, Denmark
| | - Mathias Rathe
- Department of Pediatrics Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Zhao L, Cheng X, Zhao H, Zhao H, Di W, Mei Z. Long‑term survival after comprehensive treatment in a patient with advanced neuroendocrine neoplasm of the pancreas: A case report. Oncol Lett 2025; 29:49. [PMID: 39564371 PMCID: PMC11574579 DOI: 10.3892/ol.2024.14795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 10/11/2024] [Indexed: 11/21/2024] Open
Abstract
Neuroendocrine neoplasms of the pancreas (pNENs) are rare. In February 2021, a 54-year-old woman was diagnosed with pNEN and multiple metastases within the liver. The patient, diagnosed with grade G2 neuroendocrine neoplasm (T4N0M1), underwent an ultrasonography-guided liver biopsy and radiofrequency ablation. After receiving Sandostatin LAR in April 2021, side effects led to its discontinuation after seven cycles. Following two sessions of radiofrequency ablation, the patient's condition was stable. However, disease progression was noted in September 2023, resulting in hemodialysis and closed peritoneal drainage. Surufatinib was administered, stabilizing the tumor by November 2023. The patient underwent transarterial chemoembolization due to a large tumor burden, with subsequent MRCP showing stability from diagnosis in February 2021 to June 2024. The present case report highlights the role of tailored treatment strategies considering patient comorbidities and tumor biology, and the significance of secondary puncture biopsy, which, despite not being pursued by the patient in the present study due to the associated risks, may provide survival benefits for patients with advanced or metastatic pNEN.
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Affiliation(s)
- Lei Zhao
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Xin Cheng
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Hongbin Zhao
- Department of General Surgery, Huaihai Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
| | - Haifei Zhao
- Department of Imaging, Huaihai Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
| | - Wenyu Di
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China
| | - Zhihong Mei
- Department of Radiotherapy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China
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Bousi SE, Zachiotis M, Papapanou M, Frountzas M, Symeonidis D, Raptis D, Papaziogas B, Toutouzas K, Felekouras E, Schizas D. Robotic Versus Laparoscopic Versus Open Surgery for Non-Metastatic Pancreatic Neuroendocrine Tumors (pNETs): A Systematic Review and Network Meta-Analysis. J Clin Med 2024; 13:6303. [PMID: 39518444 PMCID: PMC11546742 DOI: 10.3390/jcm13216303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/09/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
Background: This systematic review, using pairwise and network meta-analyses, aimed to compare the intraoperative, short-term, and long-term postoperative outcomes of minimally invasive surgery (MIS) and open surgery (OS) for the management of pancreatic neuroendocrine tumors (pNETs). Methods: Studies reporting on the effects of robotic, laparoscopic, and open surgery on pNETs published before November 2023 on PubMed, Scopus, and CENTRAL were analyzed. Results: Thirty-two studies with 5379 patients were included in this review, encompassing 2251 patients undergoing MIS (1334 laparoscopic, 508 robotic, and 409 unspecified MIS) and 3128 patients undergoing OS for pNETs management. Pairwise meta-analysis revealed that the MIS group had a significantly shorter length of hospital stay ((a low certainty of evidence), MD of -4.87 (-6.19 to -3.56)); less intraoperative blood loss ((a low certainty of evidence), MD of -108.47 (-177.47 to -39.47)); and decreased tumor recurrence ((a high certainty of evidence), RR of 0.46, 95% CI (0.33 to 0.63)). Subgroup analysis indicated a higher R0 resection rate and prolonged operative time for laparoscopic surgery than for OS. The network meta-analysis ranked the robotic approach as superior in terms of the length of hospital stay, followed by the laparoscopic and OS arms. Furthermore, it favored both MIS approaches over OS in terms of the R0 resection rate. No significant differences were found in severe postoperative complications, postoperative fistula formation, mortality, readmission, reoperation, or conversion rates. Conclusions: This review supports the safety of MIS for the treatment of pNETs. However, the varying certainty of evidence emphasizes the need for higher-quality studies.
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Affiliation(s)
- Stelios-Elion Bousi
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece; (S.-E.B.); (M.P.); (E.F.)
| | - Marinos Zachiotis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece; (S.-E.B.); (M.P.); (E.F.)
| | - Michail Papapanou
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece; (S.-E.B.); (M.P.); (E.F.)
| | - Maximos Frountzas
- First Propaedeutic Department of Surgery, National and Kapodistrian University of Athens, Hippocration General Hospital, 11527 Athens, Greece; (M.F.); (K.T.)
| | | | - Dimitrios Raptis
- Second Department of Surgery, Aristotle University of Thessaloniki, G. Gennimatas Hospital, 54635 Thessaloniki, Greece
| | - Basilios Papaziogas
- Second Department of Surgery, Aristotle University of Thessaloniki, G. Gennimatas Hospital, 54635 Thessaloniki, Greece
| | - Konstantinos Toutouzas
- First Propaedeutic Department of Surgery, National and Kapodistrian University of Athens, Hippocration General Hospital, 11527 Athens, Greece; (M.F.); (K.T.)
| | - Evangelos Felekouras
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece; (S.-E.B.); (M.P.); (E.F.)
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece; (S.-E.B.); (M.P.); (E.F.)
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Li K, Chen T, Duan B, Ji Y, Li J, Xu M. A retrospective analysis of 26 cases of duodenal neuroendocrine tumor treated by endoscopic submucosal dissection. Indian J Cancer 2024; 61:849-857. [PMID: 39960722 DOI: 10.4103/ijc.ijc_265_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 01/10/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Duodenal neuroendocrine tumors (D-NETs) are rare but clinically significant tumors that can occur in various parts of the duodenum, including the duodenal papilla. Endoscopic submucosal dissection (ESD) has emerged as a minimally invasive treatment option for D-NETs, offering potential advantages in terms of tumor removal and postoperative recovery. We aimed to retrospectively analyze the clinical characteristics and prognosis of ESD for D-NETs. METHODS A total of 26 cases of duodenal neuroendocrine tumors (27 lesions), including duodenal papillary neuroendocrine tumors, were studied retrospectively. RESULTS A total of 26 patients with D-NETs (27 lesions) were pathologically diagnosed, and 27 lesions were found by chance during endoscopy. The lesions included duodenal bulbar, descending part, and duodenal papilla. Nineteen tumors were <1 cm (70.4%) in diameter, and eight tumors were 1-2 cm (29.6%) in diameter. There were five cases of duodenal papilla NETs. G1: 24 (88.8%) and G2: 3 (11.1%). Endoscopic ultrasonography showed that 27 lesions were confined to the submucosa. One case was a neuroendocrine tumor 2 mm inside a tubular adenoma at the papilla. All operations were performed by senior doctors in the department. The total resection rate was 100%, and the incidence of intraoperative bleeding and perforation was 0. Delayed bleeding and perforation were 0. The shortest operation time was 25 min, and the longest was 70 min. Burning tumor cells at the basal resection margin were noted in 11 lesions, necessitating careful pathological assessment. There were 24 cases of G1 type and 3 cases of G2 type. All 26 patients underwent abdominal CT before operation to confirm the absence of lymph node and distal metastasis. One patient with papillary lesion had positive lesion base resection and was treated with additional operation. Temporary biliary and pancreatic duct stents were placed before or after ESD in all five cases of duodenal papillary lesions, and no biliary and pancreatic complications occurred after surgery. Postoperative follow-up gastroscopy and abdominal CT confirmed no recurrence or metastasis during a follow-up period of 3 months to 4.5 years. There was no recurrence or metastasis during a follow-up period of 3 months to 4 ½ years. CONCLUSION ESD may be an effective and safe intervention for D-NETs ≤20 mm confined to the mucosa or submucosa of the duodenum, including the papilla. Clinicians should remain vigilant about potential complications during and after surgery. Duodenal ESD treatment NET has high requirements in terms of treatment technology, and clinicians should pay attention to the potential complications of ESD during operation.
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Affiliation(s)
- Kehan Li
- Endoscopy Center Department of Gastroenterology, Shanghai East Hospital, Shanghai, China
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Cavalcoli F, Rausa E, Ferrari D, Rosa R, Maccauro M, Pusceddu S, Sabella G, Cantù P, Vitellaro M, Coppa J, Mazzaferro V. Pathological Characteristics, Management, and Prognosis of Rectal Neuroendocrine Tumors: A Retrospective Study from a Tertiary Hospital. Diagnostics (Basel) 2024; 14:1881. [PMID: 39272666 PMCID: PMC11394532 DOI: 10.3390/diagnostics14171881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/22/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Rectal neuroendocrine tumors (rNENs) are rare, constituting 1-2% of rectal tumors, and are often asymptomatic, leading to challenges in early diagnosis. Current management guidelines recommend endoscopic resection for small lesions and surgical intervention for larger or high-risk tumors. This study aims to retrospectively analyze the pathological characteristics, management, and prognosis of rNEN patients. METHODS Data from the Neuroendocrine Tumor Registry at a tertiary hospital in Milan, Italy from 2005 to 2023 were retrospectively analyzed. Patient demographics, disease characteristics, pathology findings, treatment details, and surveillance data were collected. Statistical analyses included descriptive statistics, multivariable binary logistic regression, and Kaplan-Meier survival analysis. RESULTS Forty-five patients were included, 53.3% male with a mean age of 57.5 years. Most patients were asymptomatic, with incidental diagnosis during colonoscopy. Endoscopic excision was the primary treatment modality (77.8%), with surgical resection reserved for incomplete or inappropriate endoscopic resections. Disease progression occurred in 13 patients (28.9%), with tumor-related mortality of 22.2%. Kaplan-Meier analysis showed 5- and 10-year survival rates of 68.8% and 59.1%, respectively, with corresponding progression-free survival rates of 72.8% and 54.0%. Tumor stage was significantly associated with disease progression on multivariable analysis (OR = 7.230, p = 0.039). CONCLUSIONS This study highlights the heterogeneous presentation and prognosis of rNENs, with a substantial proportion diagnosed incidentally. Endoscopic management was predominantly utilized, aligning with current guidelines for localized tumors. Tumor stage emerged as a significant predictor of disease progression, emphasizing the importance of accurate staging for optimal management. Further research is warranted to refine management protocols and validate these findings.
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Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Davide Ferrari
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Roberto Rosa
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Marco Maccauro
- Departement of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Giovanna Sabella
- Department of the Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Paolo Cantù
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
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Ortigão R, Afonso LP, Pimentel-Nunes P, Dinis-Ribeiro M, Libânio D. Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:236-245. [PMID: 39022301 PMCID: PMC11250119 DOI: 10.1159/000530684] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 02/02/2023] [Indexed: 07/20/2024]
Abstract
INTRODUCTION/AIM Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). METHODS The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. RESULTS We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). CONCLUSION Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.
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Affiliation(s)
- Raquel Ortigão
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Luís Pedro Afonso
- Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
- RISE@CI-IPOP (Health Research Network, IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Unilabs Portugal, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
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Santo G, Di Santo G, Virgolini I. Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives. Semin Nucl Med 2024; 54:557-569. [PMID: 38490913 DOI: 10.1053/j.semnuclmed.2024.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/14/2024] [Accepted: 02/14/2024] [Indexed: 03/17/2024]
Abstract
Peptide receptor radionuclide therapy (PRRT) today is a well-established treatment strategy for patients with neuroendocrine tumors (NET). First performed already more than 30 years ago, PRRT was incorporated only in recent years into the major oncology guidelines, based on its proven efficacy and safety in clinical trials. Following the phase 3 NETTER-1 trial, which led to the final registration of the radiopharmaceutical Luthatera® for G1/G2 NET patients in 2017, the long-term results of the phase 3 NETTER-2 trial may pave the way for a new treatment option also for advanced G2/G3 patients as first-line therapy. The growing knowledge about the synergistic effect of combined therapies could also allow alternative (re)treatment options for NET patients, in order to create a tailored treatment strategy. The evolving thera(g)nostic concept could be applied for the identification of patients who might benefit from different image-guided treatment strategies. In this scenario, the use of dual tracer PET/CT in NET patients, using both [18F]F-FDG/[68Ga]Ga-DOTA-somatostatin analog (SSA) for diagnosis and follow-up, is under discussion and could also result in a powerful prognostic tool. In addition, alternative strategies based on different metabolic pathways, radioisotopes, or combinations of different medical approaches could be applied. A number of different promising "doors" could thus open in the near future for the treatment of NET patients - and the "key" will be thera(g)nostic!
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Affiliation(s)
- Giulia Santo
- Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria; Department of Experimental and Clinical Medicine, "Magna Graecia" University of Catanzaro, Catanzaro, Italy
| | - Gianpaolo Di Santo
- Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Irene Virgolini
- Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria.
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Qirem M, Yaghi S, Okwesili B, Atiyat R, Bains Y. A Rare Case of a Neuroendocrine Tumor at the Duodenum. Cureus 2024; 16:e57696. [PMID: 38711691 PMCID: PMC11070881 DOI: 10.7759/cureus.57696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2024] [Indexed: 05/08/2024] Open
Abstract
Neuroendocrine tumors (NETs) are slow-growing cancers derived from neuroendocrine cells that typically affect the pancreas, lungs, and gastrointestinal tract. A rare form can develop in the duodenum and can be difficult to diagnose and treat. The case below describes a rare incidence of a well-differentiated duodenal bulb NET in a 77-year-old man who had early satiety and persistent dyspepsia. Endoscopy, biopsies, and immunohistochemistry staining were used to confirm the diagnosis. According to the features of the tumor, management techniques, including endoscopic, surgical, and medicinal procedures, are being implemented.
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Affiliation(s)
- Murad Qirem
- Internal Medicine, Saint Michael's Medical Center, Newark, USA
| | - Shahd Yaghi
- Internal Medicine, Saint Michael's Medical Center, Newark, USA
| | - Byron Okwesili
- Gastroenterology and Hepatology, Saint Michael's Medical Center, Newark, USA
| | - Raed Atiyat
- Gastroenterology, Saint Michael's Medical Center, Newark, USA
| | - Yatinder Bains
- Gastroenterology, Saint Michael's Medical Center, Newark, USA
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10
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Ye JY, Fang P, Peng ZP, Huang XT, Xie JZ, Yin XY. A radiomics-based interpretable model to predict the pathological grade of pancreatic neuroendocrine tumors. Eur Radiol 2024; 34:1994-2005. [PMID: 37658884 PMCID: PMC10873440 DOI: 10.1007/s00330-023-10186-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 07/22/2023] [Accepted: 08/04/2023] [Indexed: 09/05/2023]
Abstract
OBJECTIVES To develop a computed tomography (CT) radiomics-based interpretable machine learning (ML) model to predict the pathological grade of pancreatic neuroendocrine tumors (pNETs) in a non-invasive manner. METHODS Patients with pNETs who underwent contrast-enhanced abdominal CT between 2010 and 2022 were included in this retrospective study. Radiomics features were extracted, and five radiomics-based ML models, namely logistic regression (LR), random forest (RF), support vector machine (SVM), XGBoost, and GaussianNB, were developed. The performance of these models was evaluated using a time-independent testing set, and metrics such as sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) were calculated. The accuracy of the radiomics model was compared to that of needle biopsy. The Shapley Additive Explanation (SHAP) tool and the correlation between radiomics and biological features were employed to explore the interpretability of the model. RESULTS A total of 122 patients (mean age: 50 ± 14 years; 53 male) were included in the training set, whereas 100 patients (mean age: 48 ± 13 years; 50 male) were included in the testing set. The AUCs for LR, SVM, RF, XGBoost, and GaussianNB were 0.758, 0.742, 0.779, 0.744, and 0.745, respectively, with corresponding accuracies of 73.0%, 70.0%, 77.0%, 71.9%, and 72.9%. The SHAP tool identified two features of the venous phase as the most significant, which showed significant differences among the Ki-67 index or mitotic count subgroups (p < 0.001). CONCLUSIONS An interpretable radiomics-based RF model can effectively differentiate between G1 and G2/3 of pNETs, demonstrating favorable interpretability. CLINICAL RELEVANCE STATEMENT The radiomics-based interpretable model developed in this study has significant clinical relevance as it offers a non-invasive method for assessing the pathological grade of pancreatic neuroendocrine tumors and holds promise as an important complementary tool to traditional tissue biopsy. KEY POINTS • A radiomics-based interpretable model was developed to predict the pathological grade of pNETs and compared with preoperative needle biopsy in terms of accuracy. • The model, based on CT radiomics, demonstrated favorable interpretability. • The radiomics model holds potential as a valuable complementary technique to preoperative needle biopsy; however, it should not be considered a replacement for biopsy.
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Affiliation(s)
- Jing-Yuan Ye
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Peng Fang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Zhen-Peng Peng
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, No.58 Zhongshan Er Road, Guangzhou, Guangdong, People's Republic of China
| | - Xi-Tai Huang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Jin-Zhao Xie
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Xiao-Yu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong, People's Republic of China.
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11
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Rai A, Sproule L, Larman T, Oshima K, Rhee D, Ng K, King E, Mogul D, Lemberg K. Liver transplant for primary biliary tract neuroendocrine tumor in a nine-year-old girl. Pediatr Transplant 2024; 28:e14732. [PMID: 38433619 DOI: 10.1111/petr.14732] [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: 05/18/2023] [Revised: 11/28/2023] [Accepted: 02/20/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Neuroendocrine tumors (NETs) are rare epithelial neoplasms that arise most commonly from the gastrointestinal tract. In pediatrics, the most common site of origin is in the appendix, with the liver being the most common site of metastasis. Neuroendocrine tumors arising from the biliary tract are extremely rare. METHODS We describe a case of a nine-year-old girl who presented with obstructive cholestasis and was found to have multiple liver masses identified on biopsy as well-differentiated neuroendocrine tumor with an unknown primary tumor site. RESULT The patient underwent extensive investigation to identify a primary tumor site, including endoscopy, endoscopic ultrasound, and capsule endoscopy. The patient ultimately underwent definitive management with liver transplant, and on explant was discovered to have multiple well-differentiated neuroendocrine tumors, WHO Grade 1, with extensive infiltration into the submucosa of bile duct, consistent with primary biliary tract neuroendocrine tumor. CONCLUSION Identifying the site of the primary tumor in NETs found within the liver can be challenging. To determine if an extrahepatic primary tumor exists, workup should include endoscopy, EUS, and capsule endoscopy. Children with well-differentiated hepatic NETs, with no identifiable primary tumor, and an unresectable tumor, are considered favorable candidates for liver transplantation.
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Affiliation(s)
- Anjali Rai
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Lauren Sproule
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Biochemistry, McGill University, Montreal, Canada
| | - Tatianna Larman
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kiyoko Oshima
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Daniel Rhee
- Division of General Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kenneth Ng
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elizabeth King
- Division of Transplant Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Douglas Mogul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kathryn Lemberg
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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12
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Cigrovski Berkovic M, Coppola A, Sesa V, Mrzljak A, Lai Q. Metformin and pancreatic neuroendocrine tumors: A systematic review and meta-analysis. World J Gastroenterol 2024; 30:759-769. [PMID: 38515954 PMCID: PMC10950617 DOI: 10.3748/wjg.v30.i7.759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 12/18/2023] [Accepted: 01/23/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET. AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET. METHODS A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival. RESULTS A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with I² = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; P < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; P < 0.001). The study heterogeneity was intermediate, with I² = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET. CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department for Sport and Exercise Medicine, Faculty of Kinesiology University of Zagreb, Zagreb 10000, Croatia
| | | | - Vibor Sesa
- Department of Gastroenterology and Hepatology, Liver Transplant Center, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, Liver Transplant Center, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- Department of Medicine, School of Medicine, Zagreb 10000, Croatia
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome 00018, Italy
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13
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Ferreira B, Heredia A, Serpa J. An integrative view on glucagon function and putative role in the progression of pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC). Mol Cell Endocrinol 2023; 578:112063. [PMID: 37678603 DOI: 10.1016/j.mce.2023.112063] [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: 07/04/2023] [Revised: 08/16/2023] [Accepted: 09/02/2023] [Indexed: 09/09/2023]
Abstract
Cancer metabolism research area evolved greatly, however, is still unknown the impact of systemic metabolism control and diet on cancer. It makes sense that systemic regulators of metabolism can act directly on cancer cells and activate signalling, prompting metabolic remodelling needed to sustain cancer cell survival, tumour growth and disease progression. In the present review, we describe the main glucagon functions in the control of glycaemia and of metabolic pathways overall. Furthermore, an integrative view on how glucagon and related signalling pathways can contribute for pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC) progression, since pancreas and liver are the major organs exposed to higher levels of glucagon, pancreas as a producer and liver as a scavenger. The main objective is to bring to discussion some glucagon-dependent mechanisms by presenting an integrative view on microenvironmental and systemic aspects in pNETs and HCC biology.
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Affiliation(s)
- Bárbara Ferreira
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal
| | - Adrián Heredia
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal; Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz MB, 1649-028, Lisboa, Portugal
| | - Jacinta Serpa
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal.
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14
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Milanetto AC, Armellin C, Brigiari G, Lorenzoni G, Pasquali C. Younger Age and Parenchyma-Sparing Surgery Positively Affected Long-Term Health-Related Quality of Life after Surgery for Pancreatic Neuroendocrine Neoplasms. J Clin Med 2023; 12:6529. [PMID: 37892667 PMCID: PMC10607516 DOI: 10.3390/jcm12206529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
(1) Background: Patients with pancreatic Neuroendocrine Neoplasms (PanNENs) often have a long overall survival. We evaluated determinants of quality of life (QoL) after surgery for PanNENs. (2) Methods: Patients operated on for a PanNEN in our center (1990-2021) received three EORTC QoL questionnaires (QLQ-C30, QLQ-GI.NET21, QLQ-PAN26). Six domains were selected as outcome variables (global QoL, physical function -PF, social function -SF, disease-related worries -DRWs, pain, upper-gastrointestinal (GI) symptoms) and evaluated in relation to the clinical variables. Statistical analysis was performed using R software v 4.2.2. (3) Results: One hundred and four patients enrolled showed a good global QoL (median 83.3). Old age was a determinant of worse global QoL (p 0.006) and worse PF (p 0.003). Multiple comorbidities (p 0.002) and old age (p 0.034) were associated with pain, while male gender was related to better PF (p 0.007) and less pain (p 0.012). Patients who had undergone parenchyma-sparing surgery demonstrated better PF (p 0.037), better SF (p 0.012), and less upper-GI symptoms (p 0.047). At multivariable analysis, age (p 0.005) and type of surgery (p 0.028) were confirmed as determinants of global QoL. (4) Conclusions: In patients operated on for a PanNEN, a good HRQoL is generally reported; notably, younger age and parenchyma-sparing surgery seem to positively affect HRQoL.
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Affiliation(s)
- Anna Caterina Milanetto
- Chirurgia Generale 3, Pancreatic and Digestive Endocrine Surgery Research Group, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Claudia Armellin
- Chirurgia Generale 3, Pancreatic and Digestive Endocrine Surgery Research Group, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Gloria Brigiari
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
| | - Giulia Lorenzoni
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
| | - Claudio Pasquali
- Chirurgia Generale 3, Pancreatic and Digestive Endocrine Surgery Research Group, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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15
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Clement DSVM, Brown SE, Naghibi M, Cooper SC, Tesselaar MET, van Leerdam ME, Ramage JK, Srirajaskanthan R. Feasibility of Home Parenteral Nutrition in Patients with Intestinal Failure Due to Neuroendocrine Tumours: A Systematic Review. Nutrients 2023; 15:3787. [PMID: 37686819 PMCID: PMC10490066 DOI: 10.3390/nu15173787] [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: 08/09/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/10/2023] Open
Abstract
INTRODUCTION Maintaining adequate nutritional status can be a challenge for patients with small bowel neuroendocrine tumours (NETs). Surgical resection could result in short bowel syndrome (SBS), whilst without surgical resection there is a considerable risk of ischemia or developing an inoperable malignant bowel obstruction (IMBO). SBS or IMBO are forms of intestinal failure (IF) which might require treatment with home parenteral nutrition (HPN). Limited data exist regarding the use of HPN in patients with small bowel neuroendocrine tumours, and it is not frequently considered as a possible treatment. METHODS A systematic review was performed regarding patients with small bowel NETs and IF to report on overall survival and HPN-related complications and create awareness for this treatment. RESULTS Five articles regarding patients with small bowel NETs or a subgroup of patients with NETs could be identified, mainly case series with major concerns regarding bias. The studies included 60 patients (range 1-41). The overall survival time varied between 0.5 and 154 months on HPN. However, 58% of patients were alive 1 year after commencing HPN. The reported catheter-related bloodstream infection rate was 0.64-2 per 1000 catheter days. CONCLUSION This systematic review demonstrates the feasibility of the use of HPN in patients with NETs and IF in expert centres with a reasonable 1-year survival rate and low complication rate. Further research is necessary to compare patients with NETs and IF with and without HPN and the effect of HPN on their quality of life.
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Affiliation(s)
- Dominique S. V. M. Clement
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, UK
- Department of Gastroenterology, King’s College Hospital, London SE5 9RS, UK
| | - Sarah E. Brown
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, UK
- Department of Gastroenterology, King’s College Hospital, London SE5 9RS, UK
| | - Mani Naghibi
- Intestinal Rehabilitation Unit, St Mark’s and Northwick Park Hospitals, London HA1 3UJ, UK
| | - Sheldon C. Cooper
- Department of Gastroenterology, University Hospital Birmingham, Birmingham B75 7RR, UK
| | - Margot E. T. Tesselaar
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, ENETS Centre of Excellence, 1066 CX Amsterdam, The Netherlands
| | - Monique E. van Leerdam
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, ENETS Centre of Excellence, 1066 CX Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - John K. Ramage
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, UK
| | - Rajaventhan Srirajaskanthan
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, UK
- Department of Gastroenterology, King’s College Hospital, London SE5 9RS, UK
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16
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Popoviciu MS, Paduraru L, Nutas RM, Ujoc AM, Yahya G, Metwally K, Cavalu S. Diabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment Particularities. Int J Mol Sci 2023; 24:12676. [PMID: 37628857 PMCID: PMC10454882 DOI: 10.3390/ijms241612676] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/31/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing's syndrome, Basedow-Graves' disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.
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Affiliation(s)
- Mihaela Simona Popoviciu
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410073 Oradea, Romania; (M.S.P.); (L.P.); (S.C.)
| | - Lorena Paduraru
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410073 Oradea, Romania; (M.S.P.); (L.P.); (S.C.)
| | | | - Alexandra Maria Ujoc
- Bihor County Emergency Clinic Hospital, 410167 Oradea, Romania; (R.M.N.); (A.M.U.)
| | - Galal Yahya
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Kamel Metwally
- Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia;
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410073 Oradea, Romania; (M.S.P.); (L.P.); (S.C.)
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17
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Varghese DG, Del Rivero J, Bergsland E. Grade Progression and Intrapatient Tumor Heterogeneity as Potential Contributors to Resistance in Gastroenteropancreatic Neuroendocrine Tumors. Cancers (Basel) 2023; 15:3712. [PMID: 37509373 PMCID: PMC10378410 DOI: 10.3390/cancers15143712] [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: 05/29/2023] [Revised: 07/14/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (NENs) are a heterogenous group of tumors that are incurable when metastatic, regardless of grade. The aim of this article is to understand tumor heterogeneity and grade progression as possible contributors to drug resistance in gastroentropancreatic neuroendocrine tumors (GEP-NETs). Heterogeneity has been observed in the genetic, pathological, and imaging features of these tumors at baseline. Diagnostic challenges related to tumor sampling and the potential for changes in grade over time further confound our ability to optimize therapy for patients. A better understanding of NEN biology and tumor heterogeneity at baseline and over time could lead to the development of new therapeutic avenues.
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Affiliation(s)
- Diana Grace Varghese
- Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 94158, USA
| | - Jaydira Del Rivero
- Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 94158, USA
| | - Emily Bergsland
- UCSF Helen Diller Family Comprehensive Cancer Center and Department of Medicine, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA
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18
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Adnan A, Basu S. Somatostatin Receptor Targeted PET-CT and Its Role in the Management and Theranostics of Gastroenteropancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2023; 13:2154. [PMID: 37443548 DOI: 10.3390/diagnostics13132154] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/18/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Somatostatin receptor (SSTR) agonist-based Positron Emission Tomography-Computed Tomography (PET-CT) imaging is nowadays the mainstay for the assessment and diagnostic imaging of neuroendocrine neoplasms (NEN), especially in well-differentiated neuroendocrine tumors (NET) (World Health Organization (WHO) grade I and II). Major clinical indications for SSTR imaging are primary staging and metastatic workup, especially (a) before surgery, (b) detection of unknown primary in metastatic NET, (c) patient selection for theranostics and appropriate therapy, especially peptide receptor radionuclide therapy (PRRT), while less major indications include treatment response evaluation on and disease prognostication. Dual tracer PET-CT imaging using SSTR targeted PET tracers, viz. [68Ga]Ga-DOTA-Tyr3-Octreotate (DOTA-TATE) and [68Ga]Ga-DOTA-NaI3-Octreotide (DOTA-NOC), and fluorodeoxyglucose (FDG), have recently gained widespread acceptance for better assessment of whole-body tumor biology compared to single-site histopathology, in terms of being non-invasive and the ability to assess inter- and intra-tumoral heterogeneity on a global scale. FDG uptake has been identified as independent adverse risk factor in various studies. Recently, somatostatin receptor antagonists have been shown to be more sensitive and specific in detecting the disease. The aim of this review article is to summarize the clinical importance of SSTR-based imaging in the clinical management of neuroendocrine and related tumors.
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Affiliation(s)
- Aadil Adnan
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, JerbaiWadia Road, Parel, Mumbai 400012, India
- Homi Bhabha National Institute, Mumbai 400094, India
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, JerbaiWadia Road, Parel, Mumbai 400012, India
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19
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Schwenck J, Sonanini D, Cotton JM, Rammensee HG, la Fougère C, Zender L, Pichler BJ. Advances in PET imaging of cancer. Nat Rev Cancer 2023:10.1038/s41568-023-00576-4. [PMID: 37258875 DOI: 10.1038/s41568-023-00576-4] [Citation(s) in RCA: 73] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/17/2023] [Indexed: 06/02/2023]
Abstract
Molecular imaging has experienced enormous advancements in the areas of imaging technology, imaging probe and contrast development, and data quality, as well as machine learning-based data analysis. Positron emission tomography (PET) and its combination with computed tomography (CT) or magnetic resonance imaging (MRI) as a multimodality PET-CT or PET-MRI system offer a wealth of molecular, functional and morphological data with a single patient scan. Despite the recent technical advances and the availability of dozens of disease-specific contrast and imaging probes, only a few parameters, such as tumour size or the mean tracer uptake, are used for the evaluation of images in clinical practice. Multiparametric in vivo imaging data not only are highly quantitative but also can provide invaluable information about pathophysiology, receptor expression, metabolism, or morphological and functional features of tumours, such as pH, oxygenation or tissue density, as well as pharmacodynamic properties of drugs, to measure drug response with a contrast agent. It can further quantitatively map and spatially resolve the intertumoural and intratumoural heterogeneity, providing insights into tumour vulnerabilities for target-specific therapeutic interventions. Failure to exploit and integrate the full potential of such powerful imaging data may lead to a lost opportunity in which patients do not receive the best possible care. With the desire to implement personalized medicine in the cancer clinic, the full comprehensive diagnostic power of multiplexed imaging should be utilized.
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Affiliation(s)
- Johannes Schwenck
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany
- Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Eberhard Karls University of Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumour Therapies', Eberhard Karls University, Tübingen, Germany
| | - Dominik Sonanini
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany
- Medical Oncology and Pulmonology, Department of Internal Medicine, Eberhard Karls University of Tübingen, Tübingen, Germany
| | - Jonathan M Cotton
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumour Therapies', Eberhard Karls University, Tübingen, Germany
| | - Hans-Georg Rammensee
- Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumour Therapies', Eberhard Karls University, Tübingen, Germany
- Department of Immunology, IFIZ Institute for Cell Biology, Eberhard Karls University of Tübingen, Tübingen, Germany
- German Cancer Research Center, German Cancer Consortium DKTK, Partner Site Tübingen, Tübingen, Germany
| | - Christian la Fougère
- Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Eberhard Karls University of Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumour Therapies', Eberhard Karls University, Tübingen, Germany
- German Cancer Research Center, German Cancer Consortium DKTK, Partner Site Tübingen, Tübingen, Germany
| | - Lars Zender
- Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumour Therapies', Eberhard Karls University, Tübingen, Germany
- Medical Oncology and Pulmonology, Department of Internal Medicine, Eberhard Karls University of Tübingen, Tübingen, Germany
- German Cancer Research Center, German Cancer Consortium DKTK, Partner Site Tübingen, Tübingen, Germany
| | - Bernd J Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany.
- Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumour Therapies', Eberhard Karls University, Tübingen, Germany.
- German Cancer Research Center, German Cancer Consortium DKTK, Partner Site Tübingen, Tübingen, Germany.
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20
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Zhu C, Sandilos G, Williamson J, Emery R, Platoff R, Joneja U, Acharya NK, Lin A, Badach J, Zilberman B, Madzo J, Jelinek J, Zhang P, Hong YK. Novel treatment strategy of targeting epigenetic dysregulation in pancreatic neuroendocrine tumors. Surgery 2023; 173:1045-1051. [PMID: 36642656 DOI: 10.1016/j.surg.2022.12.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 01/15/2023]
Abstract
BACKGROUND Epigenetic dysregulation is an integral step in the progression of pancreatic neuroendocrine tumors. We hypothesized that tumor suppressor repression by DNA methyltransferase 1 in pancreatic neuroendocrine tumors could be targeted with epigenetic treatment. METHODS Resected pancreatic neuroendocrine tumors from 32 patients were stained for DNA methyltransferase 1 and scored. Human (BON1) and murine (STC) pancreatic neuroendocrine tumor cells were treated with DNA methyltransferase 1 inhibitor 5-azacytidine and chemotherapeutic agents 5-fluorouracil and temozolomide. Cell proliferation assay and tumor suppressor gene analysis were performed with qRT-PCR and Clarion S microarray. Tumor measurements were compared in a murine treatment model. RESULTS High DNA methyltransferase scores were associated with high Ki-67 (6.7% vs 70.6% P < .01), mitotic rate (0.0% vs 31.3%), and grade (20.0% vs 80.4%, P < .01). Treatment with 5-azacytidine and chemotherapy resulted in a reduction of cell proliferation compared to chemotherapy alone in BON1 (77.3% vs 53.1%, P < .001) and STC (73.4% vs 34.2%, P < .001). Treatment with 5-azacytidine and chemotherapy resulted in upregulation of tumor suppressors CDKN1A (7.6 rel. fold, P < .001), BRCA2 (4.3 rel. fold, P < .001), and CDH1 (6.0 rel. fold, P = .026) in BON1 and CDKN1a (14.5 rel. fold, P < .001) and CDH (17.5 rel. fold, P < .001) in STC. In microarray, 5-azacytidine drove global genetic changes in combination treatment. In vivo tumors treated with chemotherapy measured 88.6 ± 19.54 mm3 vs 52.89 ± 10.51 mm3 in those treated with combination therapy (P = .009). CONCLUSION Epigenetic dysregulation with DNA methyltransferase 1 is associated with pancreatic neuroendocrine tumors and is a potential targetable strategy. 5-azacytidine and chemotherapy in combination can reduce cell proliferation, upregulate silenced tumor suppressor genes, and decrease in vivo tumors in pancreatic neuroendocrine tumors.
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Affiliation(s)
- Clara Zhu
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | | | - John Williamson
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Robert Emery
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Rebecca Platoff
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Upasana Joneja
- Department of Pathology, Cooper University Hospital, Camden, NJ
| | | | - Andrew Lin
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Jeremy Badach
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Brian Zilberman
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Jozef Madzo
- Coriell Institute for Medical Research, Camden, NJ
| | | | - Ping Zhang
- Department of Surgery, Cooper University Hospital, Camden, NJ
| | - Young Ki Hong
- Department of Surgery, Cooper University Hospital, Camden, NJ.
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21
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Clement DSVM, Srirajaskanthan R, Ramage JK, Tesselaar MET, Khan MS, Verbeek WHM, Wanten GJA, Naghibi M. Outcomes and survival in patients with advanced intestinal neuroendocrine tumours on home parenteral nutrition, an international multicentre retrospective cohort study. Clin Nutr ESPEN 2023; 54:106-112. [PMID: 36963850 DOI: 10.1016/j.clnesp.2023.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 12/09/2022] [Accepted: 01/09/2023] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIMS Only limited information is available on the use of home parenteral nutrition (HPN) in patients with advanced neuroendocrine tumours (NETs) causing intestinal failure (IF). This study aims to report the outcomes of the explore the use of HPN in this patient cohort, in the largest case series to date. METHODS A retrospective study in the United Kingdom and the Netherlands was performed, using the UK National British Artificial Nutrition Survey (BANS) and local databases in the Netherlands. Data regarding age, sex, NET grading, staging, treatment, HPN characteristics and survival outcomes were collected. RESULTS Data were collected on 41 patients (n = 18 males, 44%) with a median age of 65. Most primary tumours were in the small bowel (n = 35, 85%). The NETs were Grade 1 (n = 16, 39%), Grade 2 (n = 7, 17%), Grade 3 (n = 1, 2%). In 28 patients (n = 68%) there was stage IV disease with metastases located in the peritoneum, mesentery and or liver. There were two indications for HPN; short bowel syndrome (n = 27, 66%) and inoperable malignant bowel obstruction (n = 14, 34%). The median period on HPN was 11 months (interquartile range 4-25 months). 11 patients were still alive and receiving HPN treatment after 2 years, and 6 patients after 3 years. Six patients (22%) with short bowel syndrome (SBS) could be weaned from HPN. There was a statistically significant improved survival for patients with short bowel syndrome (median 24 months) compared to inoperable malignant bowel obstruction (median 7 months). The catheter-related bloodstream infection rate was comparable to other HPN patient cohorts at 1.0 per 1000 catheter days. CONCLUSION This study shows that HPN can be used safely in patients with NET and IF to increase survival beyond that reasonably expected in the context of either short bowel syndrome or inoperable malignant bowel obstruction. Patients with short bowel syndrome are most likely to benefit. Further prospective studies are necessary to validate survival benefits and to demonstrate the effect of HPN on quality of life.
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Affiliation(s)
- Dominique S V M Clement
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King's College Hospital Denmark Hill, London SE5 9RS, United Kingdom; Department of Gastroenterology, King's College Hospital, Denmark Hill London, SE5 9RS United Kingdom.
| | - Rajaventhan Srirajaskanthan
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King's College Hospital Denmark Hill, London SE5 9RS, United Kingdom; Department of Gastroenterology, King's College Hospital, Denmark Hill London, SE5 9RS United Kingdom
| | - John K Ramage
- Kings Health Partners, ENETS Centre of Excellence, Institute of Liver Studies, King's College Hospital Denmark Hill, London SE5 9RS, United Kingdom
| | - Margot E T Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute, ENETS Centre of Excellence, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands
| | - Mohid S Khan
- South Wales Neuroendocrine Tumour Service, Department of Gastroenterology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, United Kingdom
| | - Wieke H M Verbeek
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, ENETS Centre of Excellence, Plesmanlaan 121 1066 CX Amsterdam, the Netherlands
| | - Geert J A Wanten
- Intestinal Failure Unit, Radboud University Medical Centre, Geert Groteplein 10 6525 GA Nijmegen, the Netherlands
| | - Mani Naghibi
- Department of Gastroenterology, St Mark's and Northwick Park Hospitals, Watford Road London, Harrow HA1 3UJ, United Kingdom
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22
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Reccia I, Pai M, Kumar J, Spalding D, Frilling A. Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:1861. [PMID: 36980746 PMCID: PMC10047148 DOI: 10.3390/cancers15061861] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/10/2023] [Accepted: 03/18/2023] [Indexed: 03/22/2023] Open
Abstract
Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.
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Affiliation(s)
- Isabella Reccia
- General Surgical and Oncology Unit, Policlinico San Pietro, Via Carlo Forlanini, 24036 Ponte San Pietro, Italy
| | - Madhava Pai
- Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - Jayant Kumar
- Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - Duncan Spalding
- Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - Andrea Frilling
- Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
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23
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Parghane RV, Mahajan A, Chakrabarty N, Basu S. Imaging Recommendations for Theranostic PET-CT in Oncology. Indian J Med Paediatr Oncol 2023. [DOI: 10.1055/s-0042-1760310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023] Open
Abstract
AbstractWe in this article have presented a review of the guideline recommendations on theranostic positron emission tomography-computed tomography (PET-CT) imaging which will be helpful to assist practitioners in providing appropriate patient care. Multiple guidelines by different societies and medical associations provide standards for diagnosis, imaging, and treatment of cancer patients. They have generated a number of recommendations related to 68Ga-DOTATATE and 68Ga-PSMA-11 PET-CT, which are the classical examples of theranostic PET-CT imaging in current practice.
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Affiliation(s)
- Rahul V. Parghane
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Abhishek Mahajan
- The Clatterbridge Cancer Centre NHS Foundation Trust, Pembroke Place, Liverpool, United Kingdom
| | - Nivedita Chakrabarty
- Department of Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
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24
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Stiefel R, Lehmann K, Winder T, Siebenhüner AR. What have we learnt from the past - would treatment decisions for GEP-NET patients differ between 2012 to 2016 by the new recommendations in 2022? BMC Cancer 2023; 23:148. [PMID: 36782152 PMCID: PMC9926660 DOI: 10.1186/s12885-023-10567-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/19/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs. METHODS Patients were included in this retrospective single-center analysis from 2012-2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences. RESULTS Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 - 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 - 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 - 2.89; log-rank test, p < 0.001). CONCLUSION This retrospective analysis presents a great overview of all patients', disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients' selection for upcoming clinical prospective studies.
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Affiliation(s)
- Rahel Stiefel
- grid.414526.00000 0004 0518 665XMedical Oncology and Hematology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Kuno Lehmann
- grid.7400.30000 0004 1937 0650Department of Surgery and Transplantation, University Hospital and University of Zurich, Zurich, Switzerland
| | - Thomas Winder
- grid.413250.10000 0000 9585 4754Internal Medicine II, Hematology, Oncology and Gastroenterology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria ,grid.7400.30000 0004 1937 0650University of Zurich, Zurich, Switzerland
| | - Alexander R. Siebenhüner
- grid.7400.30000 0004 1937 0650Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland ,Clinic of Internal Medicine and Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, Switzerland
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25
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Konsek-Komorowska SJ, Pęczkowska M, Kolasińska-Ćwikła AD, Cichocki A, Konka M, Roszkowska-Purska K, Ćwikła JB. Analysis of Patients with NET G1/G2 Neuroendocrine Tumors of the Small Intestine in the Course of Carcinoid Heart Disease-A Retrospective Study. J Clin Med 2023; 12:jcm12030790. [PMID: 36769439 PMCID: PMC9918269 DOI: 10.3390/jcm12030790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Neuroendocrine neoplasms of the small intestine (SI-NENs) are one of the most commonly recognized gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Carcinoid heart disease (CHD) is the primary cause of death in patients with the carcinoid syndrome (CS). The aim of this retrospective study was to evaluate possible factors impacting upon overall survival (OS) in subjects with both neuroendocrine tumors (NETs) G1/G2 of the small intestine (SI-NET) and CHD. Enrolled in our study of 275 patients with confirmed G1/G2 SI-NET, were 28 (10%) individuals with CHD. Overall survival was assessed using the Kaplan-Meier method. The Cox-Mantel test was used to determine how OS varied between groups. A Cox proportional hazards model was used to conduct univariate analyses of predictive factors for OS and estimate hazard ratios (HRs). Of the 28 individuals with confirmed carcinoid heart disease, 12 (43%) were found to have NET G1 and 16 (57%) were found to have NET G2. Univariate analysis revealed that subjects with CHD and without resection of the primary tumor had a lower OS. Our retrospective study observed that patients who presented with CHD and without resection of primary tumor had worse prognosis of survival. These results suggest that primary tumors may need to be removed when feasible, but further research is needed. However, no solid recommendations can be issued on the basis of our single retrospective study.
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Affiliation(s)
- Sonia J. Konsek-Komorowska
- Department of Cardiology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
- Correspondence:
| | - Mariola Pęczkowska
- The Cardinal Stefan Wyszyński National Institute of Cardiology, 04-628 Warsaw, Poland
| | | | - Andrzej Cichocki
- The Maria Sklodowska-Curie National Research Institute of Oncology, 02-034 Warsaw, Poland
| | - Marek Konka
- The Cardinal Stefan Wyszyński National Institute of Cardiology, 04-628 Warsaw, Poland
| | | | - Jarosław B. Ćwikła
- Department of Cardiology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
- Diagnostic and Therapeutic Center–Gammed, 02-351 Warsaw, Poland
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26
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Prediction of Pathological Grades of Pancreatic Neuroendocrine Tumors Based on Dynamic Contrast-Enhanced Ultrasound Quantitative Analysis. Diagnostics (Basel) 2023; 13:diagnostics13020238. [PMID: 36673048 PMCID: PMC9858178 DOI: 10.3390/diagnostics13020238] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/02/2023] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
Objective: To investigate whether the dynamic contrast-enhanced ultrasound (DCE-US) analysis and quantitative parameters could be helpful for predicting histopathologic grades of pancreatic neuroendocrine tumors (pNETs). Methods: This retrospective study conducted a comprehensive review of the CEUS database between March 2017 and November 2021 in Zhongshan Hospital, Fudan University. Ultrasound examinations were performed by an ACUSON Sequioa unit equipped with a 3.5 MHz 6C−1 convex array transducer, and an ACUSON OXANA2 unit equipped with a 3.5 MHz 5C−1 convex array transducer. SonoVue® (Bracco Inc., Milan, Italy) was used for all CEUS examinations. Time intensity curves (TICs) and quantitative parameters of DCE-US were created by Vuebox® software (Bracco, Italy). Inclusion criteria were: patients with histopathologically proved pNETs, patients who underwent pancreatic B-mode ultrasounds (BMUS) and CEUS scans one week before surgery or biopsy and had DCE-US imaging documented for more than 2 min, patients with solid or predominantly solid lesions and patients with definite diagnosis of histopathological grades of pNETs. Based on their prognosis, patients were categorized into two groups: pNETs G1/G2 group and pNETs G3/pNECs group. Results: A total of 42 patients who underwent surgery (n = 38) or biopsy (n = 4) and had histopathologically confirmed pNETs were included. According to the WHO 2019 criteria, all pNETs were classified into grade 1 (G1, n = 10), grade 2 (G2, n = 21), or grade 3 (G3)/pancreatic neuroendocrine carcinomas (pNECs) (n = 11), based on the Ki−67 proliferation index and the mitotic activity. The majority of the TICs (27/31) of pNETs G1/G2 were above or equal to those of pancreatic parenchyma in the arterial phase, but most (7/11) pNETs G3/pNECs had TICs below those of pancreatic parenchyma from arterial phase to late phase (p < 0.05). Among all the CEUS quantitative parameters of DCE-US, values of relative rise time (rPE), relative mean transit time (rmTT) and relative area under the curve (rAUC) were significantly higher in pNETs G1/G2 group than those in pNETs G3/pNECs group (p < 0.05). Taking an rPE below 1.09 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [58.70% to 99.80%], 67.64% [48.61% to 83.32%] and 85.78% [74.14% to 97.42%], respectively. Taking rAUC below 0.855 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [66.26% to 99.53%], 83.87% [67.37% to 92.91%] and 94.72% [88.30% to 100.00%], respectively. Conclusions: Dynamic contrast-enhanced ultrasound analysis might be helpful for predicting the pathological grades of pNETs. Among all quantitative parameters, rPE, rmTT and rAUC are potentially useful parameters for predicting G3/pNECs with aggressive behavior.
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27
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Rectal neuroendocrine neoplasms: what the radiologists should know. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4016-4031. [PMID: 35288791 DOI: 10.1007/s00261-022-03474-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023]
Abstract
Neuroendocrine neoplasms of the rectum (R-NENs) are rare; however, their incidence has increased almost threefold in the last few decades. Imaging of R-NENs includes two primary categories: anatomic/morphologic imaging comprised of endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and functional/molecular imaging comprising of planar scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). The management depends on stage, dimension, atypical features, histological grade, and lymphovascular invasion (LVI). Low-risk local R-NENs can be resected endoscopically, and high-risk or locally advanced neoplasms can be treated with radical surgery and lymphadenectomy and/or chemoradiation. The review article focuses on imaging illustrations and discusses applications of different imaging modalities in diagnosing and managing R-NENs.
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28
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Lau TS, Bossen L, Guldager Kring Rasmussen D, Karsdal M, Genovese F, Arveschoug AK, Gronbaek H, Dam G. Association between fibrosis markers and kidney function following peptide receptor radionuclide therapy in patients with neuroendocrine tumours. Scandinavian Journal of Clinical and Laboratory Investigation 2022; 82:446-453. [PMID: 36129406 DOI: 10.1080/00365513.2022.2119598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Peptide receptor radionuclide therapy (PRRT) is a treatment for neuroendocrine tumours (NET). Renal impairment is a known side effect due to kidney fibrosis. We investigated the association between novel specific fibrosis markers and kidney function following PRRT. We included 38 patients who had all finished PRRT. In serum and urine, we analysed levels of three different fibrosis markers, PRO-C6 (type VI collagen formation), PRO-C3 (type III collagen formation) and C3M (type III collagen degradation). We determined kidney function by the 51Cr-EDTA plasma clearance. We used Wilcoxon rank sum test and Spearman's rank correlation to evaluate the association between the fibrosis markers and kidney function. We included 38 NET patients, 25 small-intestinal NET, 6 pancreatic NET, 2 pulmonary NET and 5 other types of NET. Median age was 69 years (IQR: 61-73). Median time from last PRRT to inclusion was 8 months (IQR: 3-20). We found significantly increased levels of serum PRO-C6 (p = .007) and urinary PRO-C6 (p = .033) and significantly decreased levels of urinary C3M (p = .035) in patients with impaired kidney function. Further, we observed a negative association between serum PRO-C6 and kidney function (rho = -0.33, p = .04) and a positive association between urinary C3M and kidney function (rho = 0.37, p = .02). We showed an association between the three fibrosis markers, serum PRO-C6, urinary PRO-C6 and urinary C3M and kidney function. These markers may help to improve the understanding of potential pathological tissue turnover and potentially improve monitoring of kidney function after PRRT in NET patients.
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Affiliation(s)
- Tobias Stemann Lau
- Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark
| | - Lars Bossen
- Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark
| | | | | | | | | | - Henning Gronbaek
- Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark
| | - Gitte Dam
- Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark
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29
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Lucandri G, Fiori G, Lucchese S, Pende V, Farina M, Giordano M, Santoro E. Extended surgical resection for nonfunctioning duodenal neuroendocrine tumor. J Surg Case Rep 2022; 2022:rjac391. [PMID: 36081781 PMCID: PMC9448358 DOI: 10.1093/jscr/rjac391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/18/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
Duodenal neuroendocrine tumors (NETs) account for <3% of all gastrointestinal NET. Most lesions are small-sized and are located in the first or second duodenal part. Tumoral grading, evaluated by Ki67 index, strongly influences patient’s outcome. Endoscopic resection is recommended for lesions measuring <2 cm, while pancreaticoduodenectomy should be the treatment of choice for large duodenal NET; Whipple procedure should be preferred in case of duodenal origin and contiguity with gastric antrum. Involvement of surrounding structures, as well as the presence of resectable liver metastases, does not contraindicate surgical resection. Herein we report a case of a 68-year-old male, presenting with an extensive mass of the descending pre-ampullary duodenal part, with involvement of the right colon and the presence of a pericholecystic single liver metastasis. In spite of such advanced disease, surgery on the patient was successful, with an uneventful postoperative outcome.
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Affiliation(s)
- Giorgio Lucandri
- 1st Department of Surgery, San Giovanni-Addolorata Hospital , Rome , Italy
| | - Giulia Fiori
- 1st Department of Surgery, San Giovanni-Addolorata Hospital , Rome , Italy
| | - Sara Lucchese
- 1st Department of Surgery, San Giovanni-Addolorata Hospital , Rome , Italy
| | - Vito Pende
- 1st Department of Surgery, San Giovanni-Addolorata Hospital , Rome , Italy
| | - Massimo Farina
- 1st Department of Surgery, San Giovanni-Addolorata Hospital , Rome , Italy
| | - Marco Giordano
- Department of Pathology, San Giovanni-Addolorata Hospital , Rome , Italy
| | - Emanuele Santoro
- 1st Department of Surgery, San Giovanni-Addolorata Hospital , Rome , Italy
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Zhang WH, Gao HL, Liu WS, Qin Y, Ye Z, Lou X, Wang F, Zhang Y, Chen XM, Chen J, Yu XJ, Zhuo QF, Xu XW, Ji SR. A real-life treatment cohort of pancreatic neuroendocrine tumors: High-grade increase in metastases confers poor survival. Front Endocrinol (Lausanne) 2022; 13:941210. [PMID: 36034463 PMCID: PMC9399842 DOI: 10.3389/fendo.2022.941210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/15/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Tumor grade determined by the Ki67 index is the best prognostic factor for pancreatic neuroendocrine tumors (PanNETs). However, we often observe that the grade of metastases differs from that of their primary tumors. This study aimed to investigate the frequency of grade changes between primary tumors and metastases, explore its association with clinical characteristics, and correlate the findings with the prognosis. METHODS Six hundred forty-eight patients with pancreatic neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 103 patients with PanNETs who had paired primary tumors and metastases with an available Ki67 index were included. Re-evaluation of Ki67 was performed on 98 available samples from 69 patients. RESULTS Fifty cases (48.5%) had a Ki67 index variation, and 18 cases (17.5%) displayed a grade increase. Metachronous metastases showed significantly higher Ki67 index variation than synchronous metastases (P=0.028). Kaplan-Meier analyses showed that high-grade metastases compared to low-grade primary tumors were significantly associated with decreased progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027). Multivariable Cox regression analyses demonstrated that a low-grade increase to high-grade was an unfavorable and independent prognostic factor for PFS and OS (P=0.010, and P=0.041, respectively). CONCLUSIONS A high-grade increase in metastases was an unfavorable predictor of PanNETs, which emphasized the importance of accurate pathological grading and could provide a reference for clinical decision-making.
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Affiliation(s)
- Wu-Hu Zhang
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - He-Li Gao
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wen-Sheng Liu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yi Qin
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zeng Ye
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xin Lou
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Fei Wang
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yue Zhang
- The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Xue-Min Chen
- The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xian-Jun Yu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Qi-Feng Zhuo
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xiao-Wu Xu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shun-Rong Ji
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
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Kumar A, Tanwar S, Gupta S, Chetiwal R, Kumar R. Advanced metastatic pancreatic neuroendocrine tumor treated successfully with peptide receptor radionuclide therapy: a case report. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2022; 3:392-397. [PMID: 36045912 PMCID: PMC9400745 DOI: 10.37349/etat.2022.00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/12/2022] [Indexed: 11/19/2022] Open
Abstract
Neuroendocrine tumor (NET) is a rare tumor that has been observed in different sites such as lungs and throughout the gastrointestinal tract. Clinical features are usually non-specific and vary considerably depending upon the location of the tumor. Symptoms are similar to those of common conditions such as peptic ulcer disease, gastritis, irritable bowel syndrome, asthma, etc. Thus, an initial diagnosis of a NET usually occurs at an advanced stage. This report describes a case of pancreatic NET (PNET, grade 2) with liver metastasis in a 37-year-old male which was found to be inoperable due to extensive direct involvement of the proximal jejunal branches and superior mesenteric vein. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate (177Lu-DOTATATE) was administered due to the inoperability of primary PNET. Complete resolution of symptoms occurred with three cycles of PRRT.
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Affiliation(s)
- Amit Kumar
- Department of Medicine, ESIC Postgraduate Institute of Medical Sciences and Research, Basaidarapur, New Delhi 110015, India
| | - Shweta Tanwar
- Scientist C, Indian Council of Medical Research, New Delhi 110029, India
| | - Sudhish Gupta
- Department of Medicine, ESIC Postgraduate Institute of Medical Sciences and Research, Basaidarapur, New Delhi 110015, India
| | - Rajesh Chetiwal
- Department of Medicine, ESIC Postgraduate Institute of Medical Sciences and Research, Basaidarapur, New Delhi 110015, India
| | - Rohit Kumar
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana 124001, India
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Zhao Y, Yu J, Liu Y, Lyu L, Ping F, Xu L, Li W, Wang O, Xu Q, Wu W, Zhang H, Li Y. Analysis of 55 patients with multiple endocrine neoplasia type 1-associated insulinoma from a single center in China. Orphanet J Rare Dis 2022; 17:219. [PMID: 35698198 PMCID: PMC9195405 DOI: 10.1186/s13023-022-02370-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 05/29/2022] [Indexed: 11/11/2022] Open
Abstract
Objective To investigate the clinical characteristics of patients with multiple endocrine neoplasia type 1 (MEN1)-related insulinoma and their relationship with specific biochemical changes and to summarize the features of treatment options for the Chinese population with this disease and the impact on long-term prognosis. Methods “MEN1” and “insulinoma” were used when searching the Peking Union Medical College Hospital (PUMCH) medical record retrieval system to obtain clinical information about patients. We identified patients diagnosed with MEN1-associated insulinoma based on endocrinological, radiological, and pathological examinations, and subsequently analyzed their clinical data. Results A total of 55 patients with MEN1-associated insulinoma were included, including 29 (52.7%) men and 26 (47.3%) women. The parathyroid gland was the most commonly affected (78.2%), followed by the pituitary gland (69.1%) and adrenal gland (16.4%). Insulinoma was the first manifestation of MEN1 in at least 23.6% (13/55) of patients. Nineteen (34.5%) patients presented with initial symptoms of hypoglycemia before the age of 22 years. Among the 24 Patients with high serum calcium (Ca) had significantly lower serum insulin levels than those with normal serum Ca levels (p < 0.001) during hypoglycemic episodes. However, serum C-peptide level at 0.5 h and serum insulin level at 1 h was higher in patients with hypercalcemia than in patients with normal serum Ca levels in the oral glucose tolerance test (OGTT), although the differences were not statistically significant. Multifocal pancreatic neuroendocrine tumors (pNETs) were present in 38 (69.1%) patients; most of them (55.6%, 20/36) underwent multiple enucleations, and 45% (9/20) had a postoperative recurrence. Five patients (10%) who underwent distal pancreatectomy developed pancreatic insufficiency after an average of seven years. patients who underwent genetic testing, 23 (95.8%) were positive for MEN1 mutation, with mutations most commonly found in exons 2 (21.7%) and 3 (13%). Conclusions In our study, the rates of postoperative recurrence and long-term complications in patients with MEN1 with multifocal pNETs were significantly different from those in other international centers and might be related to the choice of surgical method. In addition, elevated serum Ca levels in patients with primary hyperparathyroidism may affect insulin secretion. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-022-02370-1.
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Affiliation(s)
- Yuan Zhao
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Jie Yu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yiwen Liu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Lu Lyu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Lingling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Ou Wang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Wenming Wu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huabing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China. .,Chinese Academy of Medical Sciences, 1 Shuai-Fu-Yuan Wangfujing, Dongcheng District, Beijing, 100730, China.
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China. .,Chinese Academy of Medical Sciences, 1 Shuai-Fu-Yuan Wangfujing, Dongcheng District, Beijing, 100730, China.
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Janssen QP, Gorris M, van den Broek BLJ, Besselink MG, Busch OR, van Eijck CHJ, Groot Koerkamp B, van Hooft JE, van Driel LMJW. Endoscopic ultrasonography as additional preoperative workup is valuable in half of the patients with a pancreatic body or tail lesion. HPB (Oxford) 2022; 24:809-816. [PMID: 34732301 DOI: 10.1016/j.hpb.2021.10.005] [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] [Received: 05/12/2021] [Revised: 08/05/2021] [Accepted: 10/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The management of pancreatic body and tail lesions is underexposed. It remains unclear whether endoscopic ultrasonography (EUS) increases the accuracy of the preoperative workup. This study assessed the diagnostic value and safety of EUS in addition to cross-sectional imaging in a surgical cohort of patients with pancreatic body or tail lesions. METHODS A multicenter retrospective cohort study was performed of patients who underwent distal pancreatectomy from 2010 to 2017. The composite primary outcome was the additional value of EUS, defined as: (a) EUS confirmed an uncertain diagnosis on cross-sectional imaging, (b) EUS was correct in case of discrepancy with cross-sectional imaging, or (c) EUS provided tissue diagnosis for neoadjuvant treatment. Furthermore, serious adverse events and needle tract seeding were assessed. RESULTS In total, 181 patients were included, of whom 123 (68%) underwent EUS besides cross-sectional imaging. Postoperative pathology was heterogeneous: 91 was malignant, 49 premalignant, 41 benign. Most lesions were solid (n = 117). EUS had additional value in 59/123 (48%) patients; 27/50 (54%) of cystic and 32/73 (44%) of solid lesions. No serious adverse event or needle tract seeding following EUS occurred. CONCLUSION EUS had additional value besides cross-sectional imaging in half of the patients and showed low associated risks.
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Affiliation(s)
- Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - Myrte Gorris
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
| | - Bram L J van den Broek
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
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Jaimovich R. Teranóstica: conceptos y aplicaciones. REVISTA MÉDICA CLÍNICA LAS CONDES 2022. [DOI: 10.1016/j.rmclc.2022.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Lee L, Ramos-Alvarez I, Jensen RT. Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies. Cancers (Basel) 2022; 14:1250. [PMID: 35267558 PMCID: PMC8909561 DOI: 10.3390/cancers14051250] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 12/14/2022] Open
Abstract
Purpose: Recent advances in the diagnosis, management and nonsurgical treatment of patients with advanced pancreatic neuroendocrine neoplasms (panNENs) have led to an emerging need for sensitive and useful prognostic factors for predicting responses/survival. Areas covered: The predictive value of a number of reported prognostic factors including clinically-related factors (clinical/laboratory/imaging/treatment-related factors), pathological factors (histological/classification/grading), and molecular factors, on therapeutic outcomes of anti-tumor medical therapies with molecular targeting agents (everolimus/sunitinib/somatostatin analogues), chemotherapy, radiological therapy with peptide receptor radionuclide therapy, or liver-directed therapies (embolization/chemoembolization/radio-embolization (SIRTs)) are reviewed. Recent findings in each of these areas, as well as remaining controversies and uncertainties, are discussed in detail, particularly from the viewpoint of treatment sequencing. Conclusions: The recent increase in the number of available therapeutic agents for the nonsurgical treatment of patients with advanced panNENs have raised the importance of prognostic factors predictive for therapeutic outcomes of each treatment option. The establishment of sensitive and useful prognostic markers will have a significant impact on optimal treatment selection, as well as in tailoring the therapeutic sequence, and for maximizing the survival benefit of each individual patient. In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
- National Kyushu Cancer Center, Department of Hepato-Biliary-Pancreatology, Fukuoka 811-1395, Japan
| | - Irene Ramos-Alvarez
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
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Begum N, Hunold H, Gerdes B, Keck T, Waldmann A. Anxiety, Depression and Quality of Life in Patients with Neuroendocrine Neoplasia After Surgery. World J Surg 2022; 46:1408-1419. [PMID: 35194674 PMCID: PMC9054889 DOI: 10.1007/s00268-022-06479-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Neuroendocrine neoplasia (NEN) are rare and complex, with surgery as key therapy even in cases with metastasis. Little is known regarding the quality of life, prevalence of depression, anxiety and the impact of surgery. METHODS This prospective, follow-up study included 90 consecutively recruited patients with NEN after surgery in a university hospital. The EORTC QLQ-C30, EORTC QLQ-GI-NET.21, and Hospital Anxiety and Depression Scale and a hospital specific questionnaire were completed during follow-up after 3 to 5 years (t1-t5). RESULTS Mean age was 54 (SD 15) years, 13% had secondary malignancies and 11% had psychiatric diagnoses (depression n = 8, schizophrenia n = 2) pre-existent. Critical life events occurred in 51% within 5 years before diagnosis. Surgery was done in curative intention in 82% and R0-resection rate was 90%. The median survival was 25.3 years. The 10-year survival rate was 87%, 98%, 95% and 26% for all patients (n = 90), stage I/II (n = 45), stage III (n = 25) and stage IV (n = 20), respectively (p < .001). Anxiety score was pathological in 30% after 1 year (t1) and in 10% after 5 years, depression score in 25% (t1) and 30% (t5). Fatigue and muscle/body pain were elevated symptoms with > 50 and 40 points 3 years after surgery. CONCLUSION Depression rate remains high whereas anxiety declines over time. Fatigue and muscle/body pain were identified as relevantly elevated after surgery. Systematic screening and supportive therapy should be implemented during follow-up after surgery.
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Affiliation(s)
- Nehara Begum
- Department of General-, Visceral-, Thoracic- and Endocrine Surgery, Johannes Wesling Klinikum Minden, University Hospital of the Ruhr-University Bochum(RUB), Hans-Nolte Str. 1, 32429, Minden, Germany. .,Department for General Surgery, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Luebeck, Germany.
| | - Hannah Hunold
- Institute of Social Medicine and Epidemiology, University of Luebeck, Luebeck, Germany
| | - Berthold Gerdes
- Department of General-, Visceral-, Thoracic- and Endocrine Surgery, Johannes Wesling Klinikum Minden, University Hospital of the Ruhr-University Bochum(RUB), Hans-Nolte Str. 1, 32429, Minden, Germany
| | - Tobias Keck
- Department for General Surgery, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Luebeck, Germany
| | - Annika Waldmann
- Institute of Social Medicine and Epidemiology, University of Luebeck, Luebeck, Germany
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Kartal İ. Childhood neuroendocrine tumors of the digestive system: A single center experience. Medicine (Baltimore) 2022; 101:e28795. [PMID: 35147110 PMCID: PMC8830841 DOI: 10.1097/md.0000000000028795] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 01/18/2022] [Indexed: 01/04/2023] Open
Abstract
The prevalence and incidence of neuroendocrine tumors (NETs) are increasing in the pediatric population. This increase can be associated with improved diagnostics and increased detection rates of the disease. We aimed to discuss the clinical and pathological characteristics of patients with this rare disease who were followed and treated at our center.The medical records of children (aged 0-18 years) with NETs of the digestive system, followed up and treated between 2007 and 2020 at Ondokuz Mayis University Faculty of Medicine, were reviewed.Overall, 16 patients (8 girls and 8 boys) were analyzed. Fifteen patients had NETs in the appendix; 14 of these had grade I NETs, and 1 had grade II NETs. No additional surgery was performed except for appendectomy. All patients were in complete remission at the last follow-up (median 38 months). The other patient, a 12-year-old girl, had a primary hepatic neuroendocrine carcinoma (grade III NET). Three cycles of neoadjuvant and adjuvant platinum-based chemotherapy were administered, and right hepatectomy was performed to remove the mass. The patient is being followed-up for approximately 3 years without disease recurrence.Most NETs are observed in adults, and most studies have focused on this population. Unlike adults, increasing awareness of the disease in the pediatric population (especially in cases of acute appendicitis), discovering therapeutic treatments, and sharing experiences are crucial for developing an optimal therapeutic approach for pediatric NETs.
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Hua J, Shi S, Xu J, Wei M, Zhang Y, Liu J, Zhang B, Yu X. Expression Patterns and Prognostic Value of DNA Damage Repair Proteins in Resected Pancreatic Neuroendocrine Neoplasms. Ann Surg 2022; 275:e443-e452. [PMID: 32209898 DOI: 10.1097/sla.0000000000003884] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE This study aimed to examine the expression profiles and prognostic value of multiple DDR proteins in resected PanNENs. BACKGROUND DDR proteins play important roles in various cancers, including pancreatic ductal adenocarcinoma. However, the expression patterns and prognostic value of DDR proteins in PanNENs remain unclear. METHODS This retrospective analysis included PanNEN patients who underwent resection at the Fudan University Shanghai Cancer Center from 2012 to 2018. Immunohistochemical staining was performed for 12 DDR proteins in tissue microarrays. The associations of DDR protein expression and clinicopathological features with recurrence-free survival (RFS) were examined via a Cox regression model and random survival forest. A recurrence signature was constructed using recursive partitioning analysis. RESULTS In total, 131 PanNEN patients were included, with 32 (24.4%) cases of recurrence. Among the 12 DDR proteins, low checkpoint kinase 2 (CHK2) expression (P = 0.020) and loss of ataxia-telangiectasia-mutated (ATM) (P = 0.0007) significantly correlated with recurrence. Multivariable Cox regression analysis identified tumor size ≥3 cm, lymph node (LN) metastasis, high tumor grade, low CHK2 expression, and ATM loss as independent risk factors for recurrence. A recurrence signature was established based on the importance of recurrence-specific risk factors; patients with the LNnegTumorSize<3cm signature had a 5-year RFS rate of 96.8%, whereas patients with the LNposCHK2low signature had the worst 5-year RFS rate (0%). Discrimination (concordance index: 0.770) and calibration plots indicated that the recurrence signature had a good ability to identify patients at risk for recurrence. CONCLUSIONS By analyzing large-scale tissue microarrays of PanNENs, we evaluated 12 DDR protein expression profiles. We developed a recurrence signature that can identify distinct subpopulations according to RFS, which may help refine individual follow-up.
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Affiliation(s)
- Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Miaoyan Wei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Yiyin Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
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Duan H, Iagaru A, Aparici CM. Radiotheranostics - Precision Medicine in Nuclear Medicine and Molecular Imaging. Nanotheranostics 2022; 6:103-117. [PMID: 34976584 PMCID: PMC8671964 DOI: 10.7150/ntno.64141] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023] Open
Abstract
'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term theranostic was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives.
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Affiliation(s)
| | | | - Carina Mari Aparici
- Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Stanford University, Stanford, CA, USA
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Gorris M, Janssen QP, Besselink MG, van den Broek BLJ, van Eijck CHJ, van Gils MJ, Koerkamp BG, Struik F, van Driel LMJW, van Hooft JE. Sensitivity of CT, MRI, and EUS-FNA/B in the preoperative workup of histologically proven left-sided pancreatic lesions. Pancreatology 2022; 22:136-141. [PMID: 34857486 DOI: 10.1016/j.pan.2021.11.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Left-sided pancreatic lesions are often treated surgically. Accurate diagnostic work-up is therefore essential to prevent futile major abdominal surgery. Large series focusing specifically on the preoperative work-up of left-sided pancreatic lesions are lacking. This surgical cohort analysis describes the sensitivity of CT, MRI, and EUS-FNA/B in the diagnostic work-up of left-sided pancreatic lesions. METHODS We performed a post-hoc analysis of patients who underwent surgery for a left-sided pancreatic lesion between April 2010 and August 2017 and participated in the randomized CPR trial. Primary outcome was the sensitivity of CT, MRI, and EUS-FNA/B. Sensitivity was determined as the most likely diagnosis of each modality compared with the postoperative histopathological diagnosis. Additionally, the change in sensitivity of EUS versus EUS-FNA/B (i.e., cyst fluid analysis, and/or tissue acquisition) was measured. RESULTS Overall, 181 patients were included (benign: 23%, premalignant: 27%, malignant: 50%). Most patients had solid lesions (65%). Preoperative imaging included CT (86%), MRI (41%), EUS (68%). Overall, CT and EUS-FNA/B reached a sensitivity of both 71%, compared with 66% for MRI. When EUS was combined with FNA/B, sensitivity rose from 64% to 71%. For solid lesions, CT reached the highest sensitivity (75%) when compared with MRI (70%) and EUS-FNA/B (69%). For cystic lesions, EUS-FNA/B reached the highest sensitivity (75%) when compared with CT and MRI (both 62%). CONCLUSIONS CT is the most sensitive diagnostic modality for solid and EUS-FNA/B for cystic left-sided pancreatic lesions. EUS-FNA/B was associated with an increased sensitivity when compared to EUS alone.
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Affiliation(s)
- Myrte Gorris
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands; Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Bram L J van den Broek
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Marjon J van Gils
- Department of Radiology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Femke Struik
- Department of Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
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Caplin ME. Can the peptide receptor radionuclide therapy [ 177Lu]Lu-DOTA-TATE provide a net benefit for NET patients? EJC Suppl 2021; 16:1-4. [PMID: 34912477 PMCID: PMC8591180 DOI: 10.1016/j.ejcsup.2021.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 06/28/2021] [Accepted: 06/29/2021] [Indexed: 11/16/2022] Open
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Glover M, Caplin M, Leeuwenkamp OR, Longworth L. Use of [ 177Lu]Lu-DOTA-TATE in the treatment of gastroenteropancreatic neuroendocrine tumours: Results of a UK cost-effectiveness modelling study. EJC Suppl 2021; 16:14-23. [PMID: 34912479 PMCID: PMC8591195 DOI: 10.1016/j.ejcsup.2021.06.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 06/28/2021] [Accepted: 06/29/2021] [Indexed: 12/13/2022] Open
Abstract
Aim To evaluate the cost-effectiveness of [177Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs). Materials and methods A three-state partitioned survival model was developed to perform a cost-utility analysis of [177Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan–Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [177Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [177Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case). Results In GI-NETs, the incremental cost-effectiveness ratio (ICER) of [177Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [177Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively. Conclusions At a willingness to pay threshold of £30,000, [177Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).
A three-state partitioned survival model of GEP-NET patients was developed. Base case ICERs for [177Lu]Lu-DOTA-TATE were under £30,000 per QALY for all comparators. [177Lu]Lu-DOTA-TATE is cost-effective for the treatment of GEP-NETs from a NICE perspective.
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Affiliation(s)
- Matthew Glover
- PHMR Health Economics, Pricing and Reimbursement, London, UK
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Yu WM, Li R, Sun BL, Du JK, Tuo HF. Primary hepatic neuroendocrine tumour with multiple liver metastases: A case report with literature review. Int J Surg Case Rep 2021; 89:106590. [PMID: 34784532 PMCID: PMC8591487 DOI: 10.1016/j.ijscr.2021.106590] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION AND IMPORTANCE To describe an unusual case with a primary hepatic neuroendocrine tumour (PHNET) with multiple liver metastases. CASE PRESENTATION We reported a 65-year-old woman with PHNET with multiple liver metastases. She was highly suspected of having primary liver cancer with multiple intrahepatic metastases before liver biopsy, but was diagnosed with PHNET with multiple liver metastases after histopathology and immunohistochemistry (IHC) examinations. The patient successfully underwent three times of transcatheter arterial chemoembolization (TACE), and is currently living in a good state without related complications. CLINICAL DISCUSSION Neuroendocrine tumors (NETs), also known as carcinoids or argyrophilic tumors, are very rare malignant tumors. The liver is the main metastasis site of NETs, but primary hepatic neuroendocrine tumors (PHNETs) are extremely rare. Histopathology and immunohistochemistry (IHC) examinations are still the main methods used for diagnosing NETs. There are no treatment guidelines for PHNETs, and surgical resection is generally the preferred treatment. For PHNET patients who are not suitable for surgery, TACE has been proven to be an effective alternative treatment that can effectively reduce the tumour burden and relieve symptoms, but the current evidence is still limited. CONCLUSION The clinical diagnosis of PHNET still faces great challenges, imaging examinations often lead to misdiagnosis, and its diagnosis mainly depends on histopathology and immunohistochemical examinations. For PHNET patients who are not suitable for surgery, TACE may be an effective alternative therapy.
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Affiliation(s)
- Wei-Ming Yu
- Graduate School of North China University of Science and Technology, Tangshan 063210, Hebei Province, China; Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Ri Li
- Graduate School of North China University of Science and Technology, Tangshan 063210, Hebei Province, China; Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Bing-Lun Sun
- Graduate School of North China University of Science and Technology, Tangshan 063210, Hebei Province, China; Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Ji-Kang Du
- Graduate School of North China University of Science and Technology, Tangshan 063210, Hebei Province, China; Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
| | - Hong-Fang Tuo
- Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
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Baum RP, Zhang J, Schuchardt C, Müller D, Mäcke H. First-in-Humans Study of the SSTR Antagonist 177Lu-DOTA-LM3 for Peptide Receptor Radionuclide Therapy in Patients with Metastatic Neuroendocrine Neoplasms: Dosimetry, Safety, and Efficacy. J Nucl Med 2021; 62:1571-1581. [PMID: 33674401 PMCID: PMC8612334 DOI: 10.2967/jnumed.120.258889] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/16/2020] [Indexed: 12/24/2022] Open
Abstract
The objective of this study was to assess the safety, dosimetry, and efficacy of the 177Lu-labeled somatostatin receptor (SSTR) antagonist DOTA-p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (177Lu-DOTA-LM3) in patients with metastatic neuroendocrine neoplasms (NENs). Methods: Fifty-one patients (aged 27-76 y; mean, 51.6 ± 13.9 y) with metastatic NENs underwent peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-LM3 between August 2017 and December 2019. The median administered activity per cycle was 6.1 ± 0.88 GBq (range, 2.8-7.4 GBq). 68Ga-NODAGA-LM3 PET/CT was used for patient selection and follow-up after 177Lu-DOTA-LM3 PRRT. Morphologic and molecular responses were evaluated in accordance with RECIST 1.1 and the criteria of the European Organisation for Research and Treatment of Cancer (EORTC). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dosimetry was performed on 11 patients and compared with the SSTR agonist 177Lu-DOTATOC in 247 patients undergoing PRRT on the same dosimetry protocol. Results: Higher uptake and a longer effective half-life were found for 177Lu-DOTA-LM3 than for the agonist 177Lu-DOTATOC in the whole body and in the kidneys, spleen, and metastases, resulting in higher mean absorbed organ and tumor doses. All patients tolerated therapy without any serious acute adverse effects. Mild nausea without vomiting was observed in 5 (9.8%) patients; no other symptoms were reported. The most severe delayed adverse event was Common Terminology Criteria (CTC)-3 thrombocytopenia in 3 (5.9%) patients. Neither CTC-4 thrombocytopenia nor CTC-3-4 anemia or leukopenia was observed after treatment. No significant decline in renal function was observed, nor was hepatotoxicity. According to RECIST 1.1, disease control could be reached in 40 patients (disease control rate, 85.1%) of the 47 patients monitored after 177Lu-DOTA-LM3 PRRT, with a partial response in 17 (36.2%) and stable disease in 23 (48.9%), whereas 7 patients (14.9%) had progressive disease, and by EORTC criteria, there was complete remission in 2 patients (4.3%), partial remission in 21 (44.7%), stable disease in 18 (38.3%), and progressive disease in 6 (12.8%). Conclusion: The antagonist PRRT with 177Lu-DOTA-LM3 could be administered without severe adverse effects and was well tolerated by most patients, with thrombocytopenia occurring in only a few. No other severe adverse effects were observed; in particular, there was no nephrotoxicity. The SSTR antagonist 177Lu-DOTA-LM3 appears to be promising for PRRT, provides a favorable biodistribution and higher tumor radiation doses than SSTR agonists, and was effective in treating advanced metastatic NENs, especially in patients with low or no SSTR agonist binding, even achieving complete remission in some patients.
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Affiliation(s)
- Richard P Baum
- Theranostics Center for Molecular Radiotherapy and Precision Oncology, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany
- CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany
| | - Jingjing Zhang
- Theranostics Center for Molecular Radiotherapy and Precision Oncology, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany;
- Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; and
| | - Christiane Schuchardt
- Theranostics Center for Molecular Radiotherapy and Precision Oncology, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Dirk Müller
- Theranostics Center for Molecular Radiotherapy and Precision Oncology, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Helmut Mäcke
- Department of Nuclear Medicine, Medical Center, University Hospital of Freiburg, Freiburg, Germany
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Köseoğlu H, Duzenli T, Sezikli M. Gastric neuroendocrine neoplasms: A review. World J Clin Cases 2021; 9:7973-7985. [PMID: 34621854 PMCID: PMC8462212 DOI: 10.12998/wjcc.v9.i27.7973] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
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Affiliation(s)
- Hüseyin Köseoğlu
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
| | - Tolga Duzenli
- Department of Gastroenterology, Hitit University Erol Olçok Education and Research Hospital, Çorum 19200, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
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Lithgow K, Venkataraman H, Hughes S, Shah H, Kemp-Blake J, Vickrage S, Smith S, Humphries S, Elshafie M, Taniere P, Diaz-Cano S, Dasari BVM, Almond M, Ford S, Ayuk J, Shetty S, Shah T, Geh I. Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort. Sci Rep 2021; 11:17947. [PMID: 34504148 PMCID: PMC8429701 DOI: 10.1038/s41598-021-97247-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 06/21/2021] [Indexed: 11/14/2022] Open
Abstract
Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.
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Affiliation(s)
- K Lithgow
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, 1820 Richmond Rd SW, Calgary, AB, T2T 5C7, Canada.
| | - H Venkataraman
- Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Hughes
- Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - H Shah
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Kemp-Blake
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Vickrage
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Smith
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Humphries
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - M Elshafie
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - P Taniere
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Diaz-Cano
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - B V M Dasari
- Department of Liver Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - M Almond
- Department of General Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Ford
- Department of General Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Ayuk
- Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Shetty
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - T Shah
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - I Geh
- Department of Oncology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Carvão J, Dinis-Ribeiro M, Pimentel-Nunes P, Libânio D. Neuroendocrine Tumors of the Gastrointestinal Tract: A Focused Review and Practical Approach for Gastroenterologists. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 28:336-348. [PMID: 34604465 PMCID: PMC8443956 DOI: 10.1159/000512089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 10/01/2020] [Indexed: 02/05/2023]
Abstract
Neuroendocrine tumors (NETs) are rare tumors derived from the neuroendocrine cell system, and more commonly found in the gastrointestinal (GI) tract. Over the last decades, the incidence of GI-NETs has been steadily increasing, partly due to the expanding indications for endoscopy. Most patients with NETs are asymptomatic, and their NETs are noticed during screening examinations; thus, endoscopists are on the frontline of the diagnosis of GI-NETs. Since GI-NETs are less frequent than other malignancies, the natural history, diagnosis, and management of these tumors may not be fully understood. In this review, we aim to update the endoscopist on key clinical features and management of patients with gastric, duodenal, and rectal NETs.
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Affiliation(s)
- Joana Carvão
- Gastroenterology Department, Hospital Central do Funchal, Funchal, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
- Surgery and Physiology Department, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
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Ronde EM, Heidsma CM, Eskes AM, Schopman JE, Nieveen van Dijkum EJM. Health-related quality of life and treatment effects in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. Eur J Cancer Care (Engl) 2021; 30:e13504. [PMID: 34462979 PMCID: PMC9286581 DOI: 10.1111/ecc.13504] [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: 11/19/2020] [Revised: 07/29/2021] [Accepted: 07/30/2021] [Indexed: 11/30/2022]
Abstract
Introduction Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are often diagnosed in an advanced stage. As the optimal sequence of therapy remains largely unclear, all treatment‐related outcomes, including health‐related quality of life (HRQoL) prospects, should be assessed according to patients' preferences. Methods A targeted search was performed in PubMed and EMBASE to identify studies on treatment effect and HRQoL, measured using the EORTC QLQ‐C30 tool, in patients with advanced, well‐differentiated GEPNENs. Study quality was assessed, and meta‐analyses were performed for global health status/QOL and tumour response. Results The search yielded 1,322 records, and 20 studies were included, examining somatostatin analogues (SSA), peptide receptor radionuclide therapies (PRRT), chemotherapy, SSA‐based combination therapies, and targeted therapies. Global HRQoL was stable, and rates for disease stabilisation were moderate to high across all treatments. Meta‐analyses for global health status/QOL after SSA treatment were not significant (mean difference: –0.3 [95% CI: −1.3 to 0.7]). The highest pooled overall tumour response rate was 33% (95% CI: 24–45%) for PRRT. The highest pooled clinical benefit rate was 94% (95% CI: 65–99%) for chemotherapy. Conclusion All treatments appeared beneficial for disease stabilisation while maintaining stable global health status/QOL. High‐quality HRQoL reporting was lacking. HRQoL should be a central outcome next to well‐established outcomes.
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Affiliation(s)
- Elsa M Ronde
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Charlotte M Heidsma
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Anne M Eskes
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Josefine E Schopman
- Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Min LA, Castagnoli F, Vogel WV, Vellenga JP, van Griethuysen JJM, Lahaye MJ, Maas M, Beets Tan RGH, Lambregts DMJ. A decade of multi-modality PET and MR imaging in abdominal oncology. Br J Radiol 2021; 94:20201351. [PMID: 34387508 PMCID: PMC9328040 DOI: 10.1259/bjr.20201351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVES To investigate trends observed in a decade of published research on multimodality PET(/CT)+MR imaging in abdominal oncology, and to explore how these trends are reflected by the use of multimodality imaging performed at our institution. METHODS First, we performed a literature search (2009-2018) including all papers published on the multimodality combination of PET(/CT) and MRI in abdominal oncology. Retrieved papers were categorized according to a structured labelling system, including study design and outcome, cancer and lesion type under investigation and PET-tracer type. Results were analysed using descriptive statistics and evolutions over time were plotted graphically. Second, we performed a descriptive analysis of the numbers of MRI, PET/CT and multimodality PET/CT+MRI combinations (performed within a ≤14 days interval) performed during a similar time span at our institution. RESULTS Published research papers involving multimodality PET(/CT)+MRI combinations showed an impressive increase in numbers, both for retrospective combinations of PET/CT and MRI, as well as hybrid PET/MRI. Main areas of research included new PET-tracers, visual PET(/CT)+MRI assessment for staging, and (semi-)quantitative analysis of PET-parameters compared to or combined with MRI-parameters as predictive biomarkers. In line with literature, we also observed a vast increase in numbers of multimodality PET/CT+MRI imaging in our institutional data. CONCLUSIONS The tremendous increase in published literature on multimodality imaging, reflected by our institutional data, shows the continuously growing interest in comprehensive multivariable imaging evaluations to guide oncological practice. ADVANCES IN KNOWLEDGE The role of multimodality imaging in oncology is rapidly evolving. This paper summarizes the main applications and recent developments in multimodality imaging, with a specific focus on the combination of PET+MRI in abdominal oncology.
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Affiliation(s)
- Lisa A Min
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.,GROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | | | - Wouter V Vogel
- Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.,Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jisk P Vellenga
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.,Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Joost J M van Griethuysen
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.,GROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Max J Lahaye
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Monique Maas
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Regina G H Beets Tan
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.,GROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands.,Faculty or Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Doenja M J Lambregts
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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50
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Allmark A, Brubaker ML. Small cell neuroendocrine carcinoma disguised as an external hemorrhoid. JAAPA 2021; 34:35-39. [PMID: 34320538 DOI: 10.1097/01.jaa.0000742960.70174.8d] [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: 11/26/2022]
Abstract
ABSTRACT This article describes a patient who presented to the ED with persistent nausea and vomiting, constipation, weight loss, and a new complaint of an external hemorrhoid and hematochezia with stooling. Comprehensive diagnostic evaluation included imaging studies that showed extensive metastatic disease but did not identify a primary neoplasm. Biopsy of the external hemorrhoid revealed small cell neuroendocrine carcinoma of the anal canal.
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Affiliation(s)
- Amelia Allmark
- At the time this article was written, Amelia Allmark was a student in the PA program at Northern Arizona University in Phoenix. She now practices in oncology/hematology with Utah Cancer Specialists at the Jordan Valley Hospital in West Jordan, Utah. Mary L. Brubaker is an associate clinical professor in the PA program at Northern Arizona University. The authors have disclosed no potential conflicts of interest, financial or otherwise
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