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Arjunan D, Grossman AB, Singh H, Rai R, Bal A, Dutta P. A Long Way to Find a Small Tumor: The Hunt for an Insulinoma. JCEM CASE REPORTS 2024; 2:luae192. [PMID: 39465233 PMCID: PMC11505447 DOI: 10.1210/jcemcr/luae192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Indexed: 10/29/2024]
Abstract
We report a case of a 35-year-old woman with recurrent episodes of hypoglycemia. Biochemical investigation was suggestive of hyperinsulinemic hypoglycemia, and hence a provisional diagnosis of insulinoma was made. Despite extensive investigation using magnetic resonance imaging, endoscopic ultrasound, and 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) scanning, the tumor could not be localized. Long-distance travel allowed her to undergo a 68Ga-Exendin-4 PET/CT scan that identified a lesion in the uncinate process of the pancreas, subsequently confirmed by intraoperative ultrasound. Enucleation of the 1.5-cm lesion was performed, and histopathology confirmed a well-differentiated pancreatic neuroendocrine tumor. Postoperatively, the patient has remained free of hypoglycemic episodes and has shown normalization of glucose levels. This case underscores the efficacy of 68Ga-Exendin-4 PET/CT in the localization of an occult insulinoma, facilitating timely and curative surgical intervention, and the importance of patients having access to such a facility when not locally available.
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Affiliation(s)
| | - Ashley B Grossman
- Green Templeton College, University of Oxford, Oxford OX26HG, UK
- ENETS Centre of Excellence, Royal Free Hospital, London NW32QG, UK
- Barts and the London School of Medicine, Queen Mary University of London, London E14NS, UK
| | - Harmandeep Singh
- Department of Nuclear Medicine, PGIMER, Chandigarh 160012, India
| | - Rakesh Rai
- Department of HPB surgery and trasplantation, King's College Hospital, Dubai, UAE
- Gulf Medical University, Sharjah, UAE
| | - Amanjit Bal
- Department of Histopathology, PGIMER, Chandigarh 160012, India
| | - Pinaki Dutta
- Department of Endocrinology, PGIMER, Chandigarh 160012, India
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Gålne A, Sundlöv A, Enqvist O, Sjögreen Gleisner K, Larsson E, Trägårdh E. Retrospective evaluation of the predictive value of tumour burden at baseline [ 68 Ga]Ga-DOTA-TOC or -TATE PET/CT and tumour dosimetry in GEP-NET patients treated with PRRT. EJNMMI REPORTS 2024; 8:24. [PMID: 39112915 PMCID: PMC11306659 DOI: 10.1186/s41824-024-00210-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 05/17/2024] [Indexed: 08/10/2024]
Abstract
PURPOSE There is a lack of validated imaging biomarkers for prediction of response to peptide receptor radionuclide therapy (PRRT). The primary objective was to evaluate if tumour burden at baseline PET/CT could predict treatment outcomes to PRRT with [177Lu]Lu-DOTA-TATE. Secondary objectives were to evaluate if there was a correlation between tumour burden and mean tumour absorbed dose (AD) during first cycle, and if mean tumour AD or the relative change of tumour burden at first follow-up PET/CT could predict progression free survival (PFS) or overall survival (OS). METHODS Patients with gastroenteropancreatic neuroendocrine tumour (GEP-NET) treated with [177Lu]Lu-DOTA-TATE PRRT were retrospectively included. Tumour burden was quantified from [68 Ga]Ga-DOTA-TOC/TATE PET/CT-images at baseline and first follow-up and expressed as; whole-body somatostatin receptor expressing tumour volume (SRETVwb), total lesion somatostatin receptor expression (TLSREwb), largest tumour lesion diameter and highest SUVmax. The relative change of tumour burden was evaluated in three categories. Mean tumour AD was estimated from the first cycle of PRRT. PFS was defined as time from start of PRRT to radiological or clinical progression. OS was evaluated as time to death. Kaplan Meier survival curves and log-rank test were used to compare PFS and OS between different groups. RESULTS Thirty-one patients had a baseline PET/CT < 6 months before treatment and 25 had a follow-up examination. Median tumour burden was 132 ml (IQR 61-302) at baseline and 71 ml (IQR 36-278) at follow-up. Twenty-two patients had disease progression (median time to progression 17.2 months) and 9 patients had no disease progression (median follow-up 28.7 months). SRETVwb dichotomized by the median at baseline was not associated with longer PFS (p = 0.861) or OS (p = 0.937). Neither TLSREwb, largest tumour lesion or SUVmax showed significant predictive value. There was a moderately strong correlation, however, between SUVmax and mean tumour AD r = 0.705, p < 0.001, but no significant correlation between SRETVwb nor TLSREwb and mean tumour AD. An increase of SRETVwb, TLSREwb or largest tumour lesion at first follow-up PET/CT was significantly correlated with shorter PFS/OS. CONCLUSION Tumour burden at baseline showed no predictive value of PFS/OS after PRRT in this small retrospective study. An increase of tumour burden was predictive of worse outcome.
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Affiliation(s)
- Anni Gålne
- Department of Medical Imaging and Physiology, Skåne University Hospital, Lund and Malmö, Sweden.
- Department of Translational Medicine, Lund University, Malmö, Sweden.
- WCMM Wallenberg Centre for Molecular Medicine, Lund, Sweden.
| | - Anna Sundlöv
- Department of Clinical Sciences, Oncology and Pathology, Skåne University Hospital, Lund University, Lund, Sweden
| | - Olof Enqvist
- Eigenvision AB, Malmö, Sweden
- Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, Sweden
| | | | - Erik Larsson
- Department of Radiation Physics, Skåne University Hospital, Lund, Sweden
| | - Elin Trägårdh
- Department of Medical Imaging and Physiology, Skåne University Hospital, Lund and Malmö, Sweden
- Department of Translational Medicine, Lund University, Malmö, Sweden
- WCMM Wallenberg Centre for Molecular Medicine, Lund, Sweden
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Kato S, Saito T, Kurahashi S, Fukami Y, Komatsu S, Kaneko K, Sano T. Simultaneous resection of a neuroendocrine tumor in an incidental Meckel's diverticulum with transabdominal preperitoneal hernial repair: a case report. Surg Case Rep 2024; 10:21. [PMID: 38231465 PMCID: PMC10794676 DOI: 10.1186/s40792-024-01821-0] [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: 09/27/2023] [Accepted: 01/12/2024] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND As laparoscopic surgery becomes more prevalent worldwide, Meckel's diverticula are increasingly being discovered incidentally during surgery. There is no consensus on whether to follow up or resect such diverticula, which are usually asymptomatic. In cases of transabdominal preperitoneal inguinal hernia repair, resection of such a diverticulum might add the risk of mesh infection. Thus, it is unclear whether simultaneous intestinal resection is advisable. CASE PRESENTATION A 64-year-old man diagnosed with a left indirect inguinal hernia underwent laparoscopic inguinal hernia repair, during which a 2-cm Meckel's diverticulum located contralateral to the mesentery of the ileum approximately 30 cm from Bauhin's valve was detected incidentally. Because of the potential risk of future complications such as hemorrhage, diverticulitis, or tumor development, wedge resection of the ileum was performed extracorporeally through an extended umbilical port site after completion of the hernia repair. Pathological examination revealed a neuroendocrine tumor (G1) in Meckel's diverticulum, which was successfully resected without any mesh infection or postoperative complications. DISCUSSION Our patient's clinical course raises two important issues. First, a Meckel's diverticulum detected incidentally during laparoscopic surgery should be resected promptly because malignant tumors within such diverticula have frequently been reported. Second, simultaneous resection with hernia repair using mesh seems to be as safe as other clean-contaminated surgery. CONCLUSIONS Management of incidental Meckel's diverticula should be selected by appropriate assessment for the risk of malignancy and complications.
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Affiliation(s)
- Shoko Kato
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Takuya Saito
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
| | - Shintaro Kurahashi
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Yasuyuki Fukami
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Shunichiro Komatsu
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Kenitiro Kaneko
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Tsuyoshi Sano
- Department of Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
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Chmiel P, Rychcik-Pazyrska P, Stec R. Defining Tumor Microenvironment as a Possible Target for Effective GEP-NENs Immunotherapy-A Systematic Review. Cancers (Basel) 2023; 15:5232. [PMID: 37958406 PMCID: PMC10648089 DOI: 10.3390/cancers15215232] [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: 09/26/2023] [Revised: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogenous and recurrent group of malignancies originating from neuroendocrine secretory cells diffused on all parts of the human body. Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) account for most NENs. Considering the abundance of possible origins, locations, and tumor specifications, there is still no consensus about optimal treatment options for these neoplasms. In light of the escalating immunotherapeutic approaches, it is crucial to define indications for such therapy in GEP-NETs. Bearing in mind the significance of pathophysiological mechanisms and tumor microenvironment (TME) impact on carcinogenesis, defining TME structure and correlation with the immune system in GEP-NETs appears essential. This paper aimed to assess the characterization of the tumor immune microenvironment for a better understanding of the possible therapeutic options in GEP-NETS. The authors performed a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 3800 articles identified through database searching, 292 were assessed for eligibility. Ultimately, 28 articles were included in the qualitative synthesis. This paper sums up the research on the immune cell infiltrates, immune checkpoint expression, cytokine profile, neoangiogenesis, and microbiome in the TME of GEP-NETs.
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Mattig I, Franke MR, Pschowski R, Brand A, Stangl K, Knebel F, Dreger H. Prevalence, one-year-incidence and predictors of carcinoid heart disease. Cardiovasc Ultrasound 2023; 21:18. [PMID: 37752548 PMCID: PMC10521535 DOI: 10.1186/s12947-023-00316-6] [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: 04/29/2023] [Accepted: 09/17/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND Carcinoid heart disease (CHD) caused by neuroendocrine tumours (NET) is associated with an increased morbidity and mortality due to valvular dysfunction and right sided heart failure. The present study aimed to assess the prevalence and one-year-incidence of CHD in NET patients. Tumour characteristics, laboratory measurements, and echocardiographic findings were evaluated to identify predictors of CHD manifestation. METHODS The study was an investigator-initiated, monocentric, prospective trial. Patients with NET without previously diagnosed CHD were included and underwent comprehensive gastroenterological and oncological diagnostics. Echocardiographic examinations were performed at baseline and after one year. RESULTS Forty-seven NET patients were enrolled into the study, 64% of them showed clinical features of a carcinoid syndrome (CS). Three patients presented with CHD at baseline and three patients developed cardiac involvement during the follow-up period corresponding to a prevalence of 6% at baseline and an incidence of 6.8% within one year. Hydroxyindoleacetic acid (5-HIAA) was identified to predict the occurrence of CHD (OR, 1.004; 95% CI, 1.001-1.006 for increase of 5-HIAA), while chromogranin A (CgA), and Kiel antigen 67 (Ki 67%) had no predictive value. Six patients with CHD at twelve-month follow-up revealed a tendency for larger right heart diameters and increased values of myocardial performance index (MPEI) at baseline compared to NET patients. CONCLUSION The prevalence at baseline and one-year-incidence of CHD was 6-7%. 5-HIAA was identified as the only marker which predict the development of CHD.
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Affiliation(s)
- Isabel Mattig
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Charité Mitte, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Berlin, Germany
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, D - 10117, Berlin, Germany
| | - Maximilian Richard Franke
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Charité Mitte, Berlin, Germany
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, D - 10117, Berlin, Germany
- Helios Klinikum Emil Von Behring, Lungenklinik Heckeshorn, Berlin, Germany
| | - Rene Pschowski
- Sankt Gertrauden Krankenhaus, Gastroenterologie, Berlin, Germany
| | - Anna Brand
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Charité Mitte, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, D - 10117, Berlin, Germany
| | - Karl Stangl
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Charité Mitte, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, D - 10117, Berlin, Germany
| | - Fabian Knebel
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Charité Mitte, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Berlin, Germany
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, D - 10117, Berlin, Germany
- Sana Klinikum Lichtenberg, Innere Medizin II: Schwerpunkt Kardiologie, Berlin, Germany
| | - Henryk Dreger
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, D - 10117, Berlin, Germany.
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Virchow Klinikum, Berlin, Germany.
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Sultana Q, Kar J, Verma A, Sanghvi S, Kaka N, Patel N, Sethi Y, Chopra H, Kamal MA, Greig NH. A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management. J Clin Med 2023; 12:5138. [PMID: 37568540 PMCID: PMC10420169 DOI: 10.3390/jcm12155138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/13/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs-both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)-have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients.
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Affiliation(s)
- Qamar Sultana
- Department of Medicine, Deccan College of Medical Sciences, Hyderabad 500058, India;
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
| | - Jill Kar
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, Lady Hardinge Medical College, New Delhi 110001, India
| | - Amogh Verma
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Rama Medical College Hospital and Research Centre, Hapur 245304, India
| | - Shreya Sanghvi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai 400022, India
| | - Nirja Kaka
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Neil Patel
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Yashendra Sethi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun 248001, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India;
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China;
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1216, Bangladesh
- Enzymoics, Hebersham, NSW 2770, Australia
- Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia
| | - Nigel H. Greig
- Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
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Lv B, Wang K, Wei N, Yu F, Tao T, Shi Y. Diagnostic value of deep learning-assisted endoscopic ultrasound for pancreatic tumors: a systematic review and meta-analysis. Front Oncol 2023; 13:1191008. [PMID: 37576885 PMCID: PMC10414790 DOI: 10.3389/fonc.2023.1191008] [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: 03/21/2023] [Accepted: 07/13/2023] [Indexed: 08/15/2023] Open
Abstract
Background and aims Endoscopic ultrasonography (EUS) is commonly utilized in the diagnosis of pancreatic tumors, although as this modality relies primarily on the practitioner's visual judgment, it is prone to result in a missed diagnosis or misdiagnosis due to inexperience, fatigue, or distraction. Deep learning (DL) techniques, which can be used to automatically extract detailed imaging features from images, have been increasingly beneficial in the field of medical image-based assisted diagnosis. The present systematic review included a meta-analysis aimed at evaluating the accuracy of DL-assisted EUS for the diagnosis of pancreatic tumors diagnosis. Methods We performed a comprehensive search for all studies relevant to EUS and DL in the following four databases, from their inception through February 2023: PubMed, Embase, Web of Science, and the Cochrane Library. Target studies were strictly screened based on specific inclusion and exclusion criteria, after which we performed a meta-analysis using Stata 16.0 to assess the diagnostic ability of DL and compare it with that of EUS practitioners. Any sources of heterogeneity were explored using subgroup and meta-regression analyses. Results A total of 10 studies, involving 3,529 patients and 34,773 training images, were included in the present meta-analysis. The pooled sensitivity was 93% (95% confidence interval [CI], 87-96%), the pooled specificity was 95% (95% CI, 89-98%), and the area under the summary receiver operating characteristic curve (AUC) was 0.98 (95% CI, 0.96-0.99). Conclusion DL-assisted EUS has a high accuracy and clinical applicability for diagnosing pancreatic tumors. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023391853, identifier CRD42023391853.
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Affiliation(s)
- Bing Lv
- School of Computer Science and Technology, Shandong University of Technology, Zibo, Shandong, China
| | - Kunhong Wang
- Department of Gastroenterology, Zibo Central Hospital, Zibo, Shandong, China
| | - Ning Wei
- Department of Gastroenterology, Zibo Central Hospital, Zibo, Shandong, China
| | - Feng Yu
- Department of Gastroenterology, Zibo Central Hospital, Zibo, Shandong, China
| | - Tao Tao
- Department of Gastroenterology, Zibo Central Hospital, Zibo, Shandong, China
| | - Yanting Shi
- Department of Gastroenterology, Zibo Central Hospital, Zibo, Shandong, China
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Fields BKK, Demirjian NL, Ahmadzadehfar H, Yordanova A, Nabipour I, Jokar N, Assadi M, Joyce P, Gholamrezanezhad A. Imaging Approach to Pediatric and Adolescent Familial Cancer Syndromes. FAMILIAL ENDOCRINE CANCER SYNDROMES 2023:127-148. [DOI: 10.1007/978-3-031-37275-9_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Management of Small Nonfunctioning Pancreatic Neuroendocrine Neoplasms: Current Opinion and Controversies. J Clin Med 2022; 12:jcm12010251. [PMID: 36615051 PMCID: PMC9821009 DOI: 10.3390/jcm12010251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022] Open
Abstract
The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has increased due to the widespread use of high-resolution diagnostic imaging in screening programs. Most PNENs are slow-growing indolent neoplasms. However, a local invasion or metastasis can sometimes occur with PNENs, leading to a poor prognosis. The management of small, nonfunctioning PNENs remains under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgery remains a high-risk operation with a 28-30% morbidity and 1% mortality. Therefore, the decision on how to manage small PNENs is challenging. This review focuses on the management of small nonfunctioning PNENs. We also highlight the malignant potential of small PNENs according to tumor size, tumor grade, and tumor biomarker. Endoscopic-ultrasound-guided biopsy is recommended to evaluate the potential risk of malignancy. Furthermore, we discuss the current guidelines and future directions for the management of small PNENs.
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Gonulal B, Bilgic Y, Akbulut S, Karabulut E, Samdanci ET. Management and Survival Analysis of Gastrointestinal Neuroendocrine Tumors by Different Tumor Characteristics: Tertiary Center Experience. J Gastrointest Cancer 2022; 53:915-920. [PMID: 34524616 DOI: 10.1007/s12029-021-00709-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastrointestinal neuroendocrine tumor (GI-NET) is a group of neoplasia consisting of amine and acid producing cells with different hormonal profiles. Although the entire GIS accounts for about 2% of tumors, recent research reveals that the incidence rate has increased. Given the increasing incidence in GI-NETs, more and more extensive research is needed on this subject. In this regard, the demographic and clinicopathological features of the patients diagnosed with GI-NET and their relationship with survival were investigated in the present study. METHODS Thirty-four patients diagnosed with GI-NETs between January 2009 and December 2019 at the Department of Gastroenterology, Inonu University Faculty of Medicine were analyzed retrospectively. Gender, age, tumor localization, metastasis status, tumor number, tumor diameter, tumor grade, Ki-67 index, and the relationships of these factors with overall survival were examined. RESULTS Of the patients, 61.8% included in the study were male and 38.2% were female. The average age of the patients was 60.74 years. The most common tumor location was in the stomach (26.5%) and liver (26.5%). Apart from this, 17.6% of NETs were seen in the pancreas, 11.8% in the colon, 8.8% in the rectum, 5.9% in the small intestine, and 2.9% in the appendix. No significant relationship was observed between tumor location and gender (p = .326) and age (p = .641). The tumor diameter ranged from 0.2 cm to 13.91 cm, but the average tumor diameter was 3.84 cm. Solitary tumor was found in 51.5% of cases and multiple tumors in 48.5% of cases. The most common grade was Grade 1 with 41.2% of occurrence. The average of Ki-67 index was 18.36%. There was metastasis in 52.9% of cases. The rate of medical treatment was 48.5%. The median overall survival time of the patients was 23.1 months. In addition, 1-year overall survival was 74.9%, 2-year overall survival was 44.6%, and 5-year overall survival was 35.7%. A statistically significant difference was found between tumor grade and the presence of metastasis, and the overall survival (p = .003 and p = .005). CONCLUSIONS The tumor grade and the presence of metastasis in gastrointestinal neuroendocrine tumors were found to be the most important prognostic factors affecting overall survival.
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Affiliation(s)
- Bedia Gonulal
- Department of Internal Medicine, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | - Yilmaz Bilgic
- Department of Gastroenterology, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey.
| | - Sami Akbulut
- Department of Surgery, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | - Ertugrul Karabulut
- Department of Surgery, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
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Kabasakal L, Demirci E, Selçuk NA. Radionuclide Therapy in Neuroendocrine Tumors. RADIONUCLIDE THERAPY 2022:173-186. [DOI: 10.1007/978-3-030-97220-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Abstract
Carcinoid syndrome, a paraneoplastic condition linked with the release of multiple humoral factors, affects around 30-40% of patients with well-differentiated neuroendocrine tumours. Carcinoid syndrome has a major and unfavourable impact on patients' quality of life; it raises costs when compared to non-functioning neuroendocrine tumours; and it causes patients' lifestyles to alter, such as food, job, physical activity, and social life. Somatostatin analogues have been the first-line therapy for individuals with neuroendocrine tumours and carcinoid disease for decades. While these drugs give considerable relief from carcinoid syndrome symptoms, clinical progression is unavoidable, necessitating further research into newer treatment measures. Carcinoid tumours are sometimes difficult to diagnose because of their vague or nonspecific symptoms. There have been several advancements in all aspects of carcinoid syndrome, as well as novel therapeutics, in the previous few years. New epidemiological studies show that it is becoming more common; increasing insights into the pathogenesis of its various clinical manifestations and its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history, and management of the disease. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till November 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Recent advances", "Carcinoid syndrome", "Neuroendocrine Neoplasms" and "Carcinoid heart disease". We comprehensively reviewed the literature on the pathogenesis, clinical features, and newer treatment modalities for Carcinoid Syndrome. Recent advancements in research and management have resulted from advances in our understanding of the aetiology of carcinoid syndrome. The development of molecular indicators of aggressiveness improved serum tumour markers, and the molecular aetiology of carcinoid heart disease are all possible because of advances in molecular biology. We conducted a comprehensive review to update knowledge regarding the pathophysiology, diagnostic protocols, and current and newer treatments for carcinoid syndrome, which presently requires a multidisciplinary approach, due to the complexity of the illness's aetiology, diagnosis, and therapy.
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Cazzato RL, Hubelé F, De Marini P, Ouvrard E, Salvadori J, Addeo P, Garnon J, Kurtz JE, Greget M, Mertz L, Goichot B, Gangi A, Imperiale A. Liver-Directed Therapy for Neuroendocrine Metastases: From Interventional Radiology to Nuclear Medicine Procedures. Cancers (Basel) 2021; 13:cancers13246368. [PMID: 34944988 PMCID: PMC8699378 DOI: 10.3390/cancers13246368] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 12/25/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare and heterogeneous epithelial tumors most commonly arising from the gastroenteropancreatic (GEP) system. GEP-NENs account for approximately 60% of all NENs, and the small intestine and pancreas represent two most common sites of primary tumor development. Approximately 80% of metastatic patients have secondary liver lesions, and in approximately 50% of patients, the liver is the only metastatic site. The therapeutic strategy depends on the degree of hepatic metastatic invasion, ranging from liver surgery or percutaneous ablation to palliative treatments to reduce both tumor volume and secretion. In patients with grade 1 and 2 NENs, locoregional nonsurgical treatments of liver metastases mainly include percutaneous ablation and endovascular treatments, targeting few or multiple hepatic metastases, respectively. In the present work, we provide a narrative review of the current knowledge on liver-directed therapy for metastasis treatment, including both interventional radiology procedures and nuclear medicine options in NEN patients, taking into account the patient clinical context and both the strengths and limitations of each modality.
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Affiliation(s)
- Roberto Luigi Cazzato
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
- Oncology, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg University, 67200 Strasbourg, France;
| | - Fabrice Hubelé
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France; (F.H.); (E.O.)
| | - Pierre De Marini
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
| | - Eric Ouvrard
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France; (F.H.); (E.O.)
| | - Julien Salvadori
- Radiophysics, Institut de Cancérologie de Strasbourg Europe (ICANS), 67200 Strasbourg, France;
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospitals of Strasbourg, 67200 Strasbourg, France;
| | - Julien Garnon
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
| | - Jean-Emmanuel Kurtz
- Oncology, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg University, 67200 Strasbourg, France;
| | - Michel Greget
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
| | - Luc Mertz
- Radiophysics, University Hospitals of Strasbourg, 67000 Strasbourg, France;
| | - Bernard Goichot
- Internal Medicine, Diabetes and Metabolic Disorders, University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France;
| | - Afshin Gangi
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
- School of Biomedical Engineering and Imaging Science, King’s College London, Strand, London WC2R 2LS, UK
| | - Alessio Imperiale
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France; (F.H.); (E.O.)
- Molecular Imaging—DRHIM, IPHC, UMR 7178, CNRS/Unistra, 67037 Strasbourg, France
- Correspondence: ; Tel.: +33-3-68-76-74-48; Fax: +33-3-68-76-72-56
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Ferns GA, Shahini Shams Abadi M, Raeisi A, Arjmand MH. The Potential Role of Changes in the Glucose and Lipid Metabolic Pathways in Gastrointestinal Cancer Progression: Strategy in Cancer Therapy. Gastrointest Tumors 2021; 8:169-176. [PMID: 34722470 DOI: 10.1159/000517771] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/10/2021] [Indexed: 11/19/2022] Open
Abstract
Background Changes in cell metabolism are a well-known feature of some cancers, and this may be involved in the etiology of tumor formation and progression, as well as tumor heterogeneity. These changes may affect fatty acid metabolism and glycolysis and are required to provide the increase in energy necessary for the high rate of proliferation of cancer cells. Gastrointestinal cancers remain a difficult-to-treat cancer, particularly as they are usually diagnosed at a late stage of disease and are associated with poor outcomes. Summary Recently, the changes in the metabolic pathways, including the expression of the rate-limiting enzymes involved, have been considered to be a potential target for therapy for gastrointestinal tumors. Key Message A combination of routine chemotherapy drugs with metabolic inhibitors may improve the effectiveness of treatment.
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Affiliation(s)
- Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Brighton, United Kingdom
| | - Milad Shahini Shams Abadi
- Department of Microbiology and Immunology, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.,Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Ahmad Raeisi
- Clinical Research Development Unit, Hajar Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad-Hassan Arjmand
- Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.,Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Michael A, Nath DK. Neoadjuvant and Adjuvant Chemotherapeutic Strategy of Colorectal Mixed Adeno-Neuroendocrine Carcinomas. Cureus 2021; 13:e16645. [PMID: 34458045 PMCID: PMC8384403 DOI: 10.7759/cureus.16645] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2021] [Indexed: 02/03/2023] Open
Abstract
Mixed adeno-neuroendocrine carcinomas (MANEC) is a rare pathological diagnosis characterized by the presence of both adeno-carcinomatous and neuroendocrine differentiation with each component comprising 30% of the tumor. This literature review is aimed at the extraction of all existing clinical studies and reviews on colorectal MANEC so as to ensure that a suitable chemotherapeutic regimen is chosen to improve survival outcomes and prognosis of the disease. Parallel search strategies were employed to extract past 10 years articles from PubMed, PubMed Central and Google Scholar databases. A total of 30 records consisting of one clinical trial, five retrospective cohort studies, one case control study, one case series, 16 case reports and six review papers were shortlisted. Chemotherapeutic regimens that were administered as an adjuvant and a neoadjuvant therapy were analyzed with their survival outcomes. The overall survival rate of those administered with neoadjuvant and adjuvant therapy can be as high as 57.4% and 69%, respectively. Multiple chemotherapeutic regimens were employed in colorectal MANEC and superiority of one regimen over the other can’t be established. Any drug or combination of drugs that is responsive against either of the MANEC components is found to be effective against the tumor. However, excellent responsiveness has been found with 5-fluorouracil regimens as a neoadjuvant therapy and platinum-based combinations as an adjuvant therapy. XELOX, streptozocin and S1 regimens also prove to be drugs of choice in aggressive and metastasized disease conditions. Our analysis allows for improved chemotherapeutic management of individuals with colorectal MANEC and establishes an increased potential for use of streptozocin therapy in the clinical setting. However, newer drugs like amrubicin require further research prior to describing its efficacy in colorectal MANEC.
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Affiliation(s)
- Anita Michael
- Internal Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, IND
| | - Debashis K Nath
- Internal Medicine, Queen Elizabeth Hospital Kings Lynn, King's Lynn, GBR
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Exploration of Novel Prognostic Markers in Grade 3 Neuroendocrine Neoplasia. Cancers (Basel) 2021; 13:cancers13164232. [PMID: 34439386 PMCID: PMC8393440 DOI: 10.3390/cancers13164232] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/06/2021] [Accepted: 08/22/2021] [Indexed: 11/06/2022] Open
Abstract
Simple Summary High grade neuroendocrine tumours and carcinomas (NETs/NECs) behave aggressively and have limited survival outcomes. The mainstay of therapy is systemic therapy, in which the associated side-effects are a key consideration in a palliative population. We have conducted a retrospective review of patients with high grade NETs and NECs to determine possible tests that will predict survival before patients start treatment. This will allow patients to avoid potentially toxic treatment that is unlikely to be of benefit. Abstract Background: High-grade neuroendocrine tumours and carcinomas (NET/NECs) behave aggressively, typically presenting at an advanced stage. Prognosis is poor, with median survival between 5 and 34 months. The mainstay of treatment is palliative systemic therapy. However, therapy carries a risk of toxicity, which can reduce quality of life. Therefore, accurate prognostic scores for risk stratification of patients with high-grade NET/NECs are needed to help guide patient management to decide whether active treatment is likely to improve overall survival (OS). We aimed to compare the prognostic ability of published prognostic scores to predict OS in a cohort of patients with high-grade NET/NECs of any primary site. Methods: Treatment, biochemical and clinicopathological data were collected retrospectively from 77 patients with high-grade NET/NECs across three hospitals between 2016 and 2020. Variables including performance status (PS), Ki-67, age at diagnosis, previous treatment and presence of liver metastases were recorded. Pre-treatment neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, modified Glasgow prognostic score (mGPS), and gastrointestinal neuroendocrine carcinoma (GI-NEC) score were derived. Univariable and multivariable survival analyses were used to assess prognostic ability. Results: The median age of the cohort was 63 years (range: 31–85); 53% of subjects were female. Grade 3 NETs (G3-NETs) were identified in 32 patients and NECs in 45 patients. The median OS was 13.45 months (range: 0.87–65.37) with no difference observed between G3-NETs and NECs. Univariable analysis revealed that NLR (n = 72, p = 0.049), mGPS (n = 56, p = 0.003), GI-NEC score (n = 27, p = 0.0007) and Ki-67 (n = 66, p = 0.007) were significantly associated with OS. Multivariable analysis confirmed that elevated mGPS (p = 0.046), GI-NEC score (p = 0.036), and Ki-67 (p = 0.02) were independently prognostic for reduced OS across the entire cohort. mGPS was identified as an independent prognostic factor in G3-NETs. Independent predictors of OS in NECs were PS and Ki-67. Conclusions: mGPS, PS and Ki-67 are independent prognostic markers in high-grade NET/NEC patients. Our study supports the use of these prognostic scores for risk stratification of patients with high grade cancers and as useful tools to guide treatment decisions.
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Ling D, Chirchir M, Alzahrani N, Morris DL. Small cell neuroendocrine carcinoma arising in cystic duplication of colon. ANZ J Surg 2021; 92:608-610. [PMID: 34319648 DOI: 10.1111/ans.17105] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 07/19/2021] [Indexed: 11/30/2022]
Affiliation(s)
- David Ling
- Liver and Peritonectomy Unit, St George Hospital, Sydney, New South Wales, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Magdalene Chirchir
- Department of Anatomical Pathology, SEALS Kogarah, St George Hospital, Sydney, New South Wales, Australia
| | - Nayef Alzahrani
- Liver and Peritonectomy Unit, St George Hospital, Sydney, New South Wales, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - David L Morris
- Liver and Peritonectomy Unit, St George Hospital, Sydney, New South Wales, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
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18
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Use of healthcare REsources and associated COsts in controlled versus uncontrolled carcinoid SYndrome in patients with neuroendocrine tumours: the RECOSY study. Clin Transl Oncol 2021; 23:2046-2056. [PMID: 34109562 PMCID: PMC8390421 DOI: 10.1007/s12094-021-02608-7] [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: 02/22/2021] [Accepted: 03/22/2021] [Indexed: 10/29/2022]
Abstract
PURPOSE To report healthcare resource use and associated costs in controlled versus uncontrolled carcinoid syndrome (CS) in patients with neuroendocrine tumours. METHODS A cross-sectional, non-interventional multicentre study was conducted with retrospective data analysis. Resource use was compared between two patient groups: those with controlled CS (> 12 months with no uncontrolled CS episodes) and uncontrolled CS (< 12 months since last uncontrolled episode). Patients were matched for age, sex, and origin and grade of tumour. When no matching patients were available, data from deceased patients were used. Information on healthcare resource use came from review of medical records, patient history and physician reports. Working capacity was assessed using the Work Productivity and Activity Impairment General Health questionnaire. RESULTS Twenty-six university hospitals in Spain participated, between July 2017 and April 2018. 137 patients were enrolled; 104 were analysed (2 groups of 52). Patients with uncontrolled CS had 10 times more emergency department (ED) visits (mean 1.0 vs 0.10 visits; P = 0.0167), were more likely to have a hospital admission (40.4% vs 19.2%; P = 0.0116) and had longer hospital stays (mean 7.87 vs 2.10 days; P = 0.0178) than those with controlled CS. This corresponded to higher annual hospitalisation costs (mean €5511.59 vs €1457.22; P = 0.028) and ED costs (€161.25 vs €14.85; P = 0.0236). The mean annual total healthcare costs were 60.0% higher in patients with uncontrolled than controlled CS (P = NS). CONCLUSION This study quantifies higher health resource use, and higher hospitalisation and ED costs in patients with uncontrolled CS. Better control of CS may result 3in lower medical costs.
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19
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Song IH, Lee YS, Sun DI, Hong YK, Lee KY. Metachronous double primary neuroendocrine tumors in larynx and lung: a case report. J Int Med Res 2021; 48:300060520962928. [PMID: 33167723 PMCID: PMC7658525 DOI: 10.1177/0300060520962928] [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] [Indexed: 11/16/2022] Open
Abstract
When a patient harbors two or more neuroendocrine tumors (NETs), it can be difficult to determine whether they are double primary tumors or metastases. A 60-year-old man complained of voice change lasting 1 month. On physical examination and imaging, a 1.8-cm mass was observed in his epiglottis, and a laser epiglottectomy was performed. Upon microscopic examination, the tumor consisted of medium-sized ovoid or short spindle cells. Immunohistochemical staining of the tumor cells was positive for synaptophysin, chromogranin, and calcitonin but negative for CD56; the Ki-67 proliferation index was approximately 5%. The patient was diagnosed with atypical carcinoid tumor. In 2015, a hypermetabolic endobronchial tumor was identified in the left lower lobe by positron emission tomography-computed tomography. Bronchoscopic biopsy revealed palisading large tumor cells with high nuclear-cytoplasmic ratio, frequent mitoses, and necrosis. The tumor cells were positive for CD56 and negative for cytokeratin-7, thyroid transcription factor-1, P40, synaptophysin, chromogranin, and calcitonin; the Ki-67 proliferation index was approximately 90%. Overall histologic findings were consistent with large cell neuroendocrine carcinoma rather than metastatic atypical carcinoid tumor. Detailed clinical and pathological review are essential to differentiate between metastatic NET and double primary NETs and, therefore, to provide the best management of the patient.
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Affiliation(s)
- In Hye Song
- Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Youn Soo Lee
- Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong-Il Sun
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yong-Kil Hong
- Department of Neurosurgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyo-Young Lee
- Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Giordano G, D'Adda T, Pizzi S, Campanini N, Gambino G, Berretta R. Neuroendocrine small cell carcinoma of the cervix: A case report. Mol Clin Oncol 2021; 14:92. [PMID: 33767861 PMCID: PMC7976432 DOI: 10.3892/mco.2021.2254] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 02/08/2021] [Indexed: 12/12/2022] Open
Abstract
Merkel cell polyomavirus (MCPyV) has been found in patients with Merkel cell carcinoma and respiratory tract infections. Merkel cell carcinoma is a primary aggressive neuroendocrine carcinoma of the skin. It has been demonstrated that MCPyV can be transmitted during sexual activity and may be present in the oral and anogenital mucosa. The aim of the present study was to evaluate whether MCPyV coexisted with HPV in three cases of neuroendocrine small cell carcinoma of the cervix using PCR and immunohistochemical analysis Three cases of NSC of the cervix were identified in the pathology archives of Parma University (Italy). Of these, two cases were associated with an adenocarcinomatous component. A set of general primers from the L1 region (forward, L1C1 and reverse, L1C2 or L1C2M) was PCR amplified to detect the broad-spectrum DNA of genital HPV. The presence of MCPyV was investigated via immunohistochemistry using a mouse monoclonal antibody against the MCPyV LT antigen and through PCR analysis to separate viral DNA. HPV DNA was present in all three neuroendocrine carcinomas and in the adenocarcinoma component of the two mixed cases. None of the cases were immunoreactive to CM2B4 and did not contain viral DNA in either their neuroendocrine or adenocarcinomatous component. Whilst it is difficult to draw definitive conclusions from such a small sample size, these data suggested that MCPyV does not coexist with HPV in the cervix. However, in the present study, the absence of detectable MCPyV may have been due to the presence of a genotype that was not detected by the primers used in the PCR analysis or by the antibody used for the immunohistochemical study. MCPyV microRNA may also have been present, inhibiting LT expression. Additional studies with larger cohorts and more advanced molecular biology techniques are required to confirm the hypothesis of the current study.
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Affiliation(s)
- Giovanna Giordano
- Department of Medicine and Surgery, Pathology Unit, University of Parma, Gramsci, I-43126 Parma, Italy
| | - Tiziana D'Adda
- Department of Medicine and Surgery, Pathology Unit, University of Parma, Gramsci, I-43126 Parma, Italy
| | - Silvia Pizzi
- Department of Medicine and Surgery, Pathology Unit, University of Parma, Gramsci, I-43126 Parma, Italy
| | - Nicoletta Campanini
- Department of Medicine and Surgery, Pathology Unit, University of Parma, Gramsci, I-43126 Parma, Italy
| | - Giulia Gambino
- Department of Obsterics and Gynecology, University of Parma, Gramsci, I-43126 Parma, Italy
| | - Roberto Berretta
- Department of Obsterics and Gynecology, University of Parma, Gramsci, I-43126 Parma, Italy
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Baeg K, Harris C, Naparst MS, Ahn E, Thapi S, Martin J, Rustgi S, Mhango G, Wisnivesky J, Kim MK. Effect of treatment center volume on outcomes in gastroenteropancreatic neuroendocrine tumor patients. BMC Cancer 2021; 21:146. [PMID: 33563241 PMCID: PMC7871611 DOI: 10.1186/s12885-021-07868-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 02/02/2021] [Indexed: 12/15/2022] Open
Abstract
Background Medical centers with varying levels of expertise treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which are relatively rare tumors. This study assesses the impact of center volume on GEP-NET treatment outcomes. Methods We used the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare claims data. The data includes patients diagnosed between 1995 and 2010 who had no health maintenance organization (HMO) coverage, participated in Medicare parts A and B, were older than 65 at diagnosis, had tumor differentiation information, and had no secondary cancer. We identified medical centers at which patients received GEP-NET treatment (surgery, chemotherapy, somatostatin analogues, or radiation therapy) using Medicare claims data. Center volume was divided into 3 tiers – low, medium, and high – based on the number of unique GEP-NET patients treated by a medical center over 2 years. We used Kaplan-Meier curves and Cox regression to assess the association between volume and disease-specific survival. Results We identified 899 GEP-NET patients, of whom 37, 45, and 18% received treatment at low, medium volume, and high-volume centers, respectively. Median disease-specific survival for patients at low and medium tiers were 1.4 years and 5.3 years, respectively, but was not reached for patients at high volume centers. Results showed that patients treated at high volume centers had better survival than those treated in low volume centers (HR: 0.63, 95% CI: 0.4–0.9), but showed no difference in outcomes between medium and high-volume centers. Conclusions Our results suggest that for these increasingly common tumors, referral to a tertiary care center may be indicated. Physicians caring for GEP-NET patients should consider early referral to high volume centers.
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Affiliation(s)
- Kiwoon Baeg
- Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA
| | - Cynthia Harris
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Monica S Naparst
- Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA
| | - Eugene Ahn
- Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA
| | - Sahityasri Thapi
- Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA
| | - Jacob Martin
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sheila Rustgi
- Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA
| | - Grace Mhango
- Department of Medicine, Division of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Juan Wisnivesky
- Department of Medicine, Division of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Michelle Kang Kim
- Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA.
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Shi D, Dong GQ, Shen KR, Pan Y, Wei SM, Chen Y, Yu RS. Primary cystic and solid neuroendocrine tumor of the retroperitoneum: A case report. Medicine (Baltimore) 2021; 100:e24054. [PMID: 33466160 PMCID: PMC7808506 DOI: 10.1097/md.0000000000024054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 12/07/2020] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Primary neuroendocrine tumors (NETs) of the retroperitoneum are extremely rare. The purpose of this case report is to highlight the unusual growth pattern and radiologic features of primary retroperitoneal NETs. PATIENT CONCERNS A 46-year-old woman was found to have a retroperitoneal cystic and solid mass during a physical checkup. DIAGNOSES The mass was mainly multiseptated in the cystic portion and had a bead-like, lobulated appearance. The solid portion showed restricted diffusion on diffusion-weighted imaging and obvious homogeneous enhancement. The cystic portion showed ring-like and septal enhancement. The patient was diagnosed with a grade 2 (G2) NET of the retroperitoneum after surgery. INTERVENTIONS The patient underwent resection of the large retroperitoneal tumor. OUTCOMES The patient returned 20 months later with tumor recurrence in the retroperitoneum. She was enrolled in a clinical trial for sulfatinib, and the mass was considerably reduced in size after 4 months. During a nearly 1.5-year follow-up, the mass gradually became slightly enlarged. The expression of somatostatin receptor 2 (SSTR2) was detected, and somatuline was administered as the current treatment. LESSONS SUBSECTIONS When a retroperitoneal mass presents as a well-defined cystic or solid hypervascular mass with a fibrous capsule, a primary retroperitoneal NET should be considered in the differential diagnosis.
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Muniraj T, Aslanian HR. Pancreatic Neuroendocrine Tumors. GERIATRIC GASTROENTEROLOGY 2021:1933-1951. [DOI: 10.1007/978-3-030-30192-7_81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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24
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Goldmann A, Clerici T. Small Intestine NETs. ENDOCRINE SURGERY COMPREHENSIVE BOARD EXAM GUIDE 2021:711-745. [DOI: 10.1007/978-3-030-84737-1_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Rossi RE, Elli L, Branchi F, Conte D, Massironi S. Double-Balloon Enteroscopy in Detecting Small-Bowel Neuroendocrine Neoplasms: A Single-Center Prospective Study. Digestion 2020; 102:722-730. [PMID: 33361694 DOI: 10.1159/000511850] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 09/28/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Small-bowel neuroendocrine neoplasm (sbNEN) diagnosis has improved with double-balloon enteroscopy (DBE). DBE efficacy in the detection of sbNENs is unknown. We aimed to report the experience at a single referral center for NENs. METHODS All consecutive patients with a suspected sbNEN selected for diagnostic DBE were enrolled. RESULTS Between 2011 and 2016, 25 patients were referred for a suspected sbNEN. In 15/25 patients, a primary NEN was detected outside the small bowel; in 4, NEN was excluded. After extensive workup, 6 patients (4 males, median age 50 years) underwent DBE (3 anterograde, 2 retrograde, and 1 both; median time: 60 min; median insertion 200 cm). DBE was positive in 3 patients: one had an ileal 2-cm NEN G1, one had an ileal 1.3-cm NEN G1, and one had an ileal 1-cm NEN G2, all surgically removed. Of the 3 other patients, one had a metastatic NEN of unknown primary, the other two had small intestinal NENs, both surgically removed (1.6-cm G1 and G2 NEN). DBE showed a sensitivity of 60% and, in absence of false-positive results, a specificity of 100%. Accuracy resulted 67%. No complications were observed. CONCLUSIONS In line with data from the literature, the present series showed that DBE is a safe and effective procedure in the diagnosis of sbNENs. Further studies are needed to better clarify the diagnostic role of DBE in the neuroendocrine tumor setting and its relationship with other techniques.
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Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan, Italy,
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy,
| | - Luca Elli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Federica Branchi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Dario Conte
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Massironi
- Division Gastroenterology, San Gerardo Hospital, University of Milano - Bicocca School of Medicine, Monza, Italy
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Caroli-Bottino A, Mauricio AS, N Pannain VL. CD57 as a routine neuroendocrine marker for liver metastasis. INDIAN J PATHOL MICR 2020; 63:38-43. [PMID: 32031120 DOI: 10.4103/ijpm.ijpm_119_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background The characterization of hepatic metastases as having neuroendocrine origins is essential and the main markers currently used are chromogranin A (CgA) and synaptophysin (Syn). However, these markers may exhibit certain limitations, and the use of CD56 and CD57 can also be considered, although, due to low specificity, their use is discouraged. Aim This study sought to compare the immunohistochemical expression of these markers in hepatic metastases of neuroendocrine neoplasms (NEN). Materials and Methods Eighteen samples, were used for immunohistochemical staining with CgA, Syn, CD56, and CD57 antibodies. The immunostaining reactions were compared according to its intensity (I), the percentage of labeled cells (P), and a final score (I × P). Statistical agreement between the markers was also evaluated. Results CD57 was expressed in the highest number of cases and also showed the most intense expression. CgA showed the highest number of cases with more than 80% positively stained area (72.2%), followed by CD57 (61.1%). The highest average score (I × P) was obtained for CD57 (9.1 ± 4.1). The best indices of agreement were between CgA and CD57 with respect to positivity (P = 0.021) and score (P = 0.014). According to the primary site, stomach/duodenum, lungs, and undetermined subgroups showed the highest average scores for CD57, followed by CgA. For the small bowel subgroup, the highest average score was obtained for CgA, followed by CD57. Conclusion Our results highlight the importance of CD57 in the evaluation of hepatic metastases of NEN and indicate that this marker should be included with CgA and Syn in routine diagnostic panels.
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Affiliation(s)
- Adriana Caroli-Bottino
- Medical Faculty, Department of Pathology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, Ilha do Fundão, Rio de Janeiro - RJ, Brazil
| | - Almir S Mauricio
- Medical Faculty, Department of Pathology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, Ilha do Fundão, Rio de Janeiro - RJ, Brazil
| | - Vera L N Pannain
- Medical Faculty, Department of Pathology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, Ilha do Fundão, Rio de Janeiro - RJ, Brazil
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Yoshida Y, Matsumoto I, Tanaka T, Yamao K, Hayashi A, Kamei K, Satoi S, Takebe A, Nakai T, Takenaka M, Takeyama Y. Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report. Surg Case Rep 2020; 6:222. [PMID: 32975612 PMCID: PMC7519021 DOI: 10.1186/s40792-020-00987-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 09/18/2020] [Indexed: 11/16/2022] Open
Abstract
Background Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion. Case presentation A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor. Conclusions Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.
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Affiliation(s)
- Yuta Yoshida
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Ippei Matsumoto
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
| | - Tomonori Tanaka
- Department of Pathology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Kentaro Yamao
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Akihiro Hayashi
- Gastroenterology, Tottori Prefectural Central Hospital, 730, Ezu, Tottori, Tottori, 680-0000, Japan
| | - Keiko Kamei
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Shumpei Satoi
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Atsushi Takebe
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Takuya Nakai
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
| | - Yoshifumi Takeyama
- Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan
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Ohki K, Igarashi T, Ashida H, Takenaga S, Shiraishi M, Nozawa Y, Ojiri H. Usefulness of texture analysis for grading pancreatic neuroendocrine tumors on contrast-enhanced computed tomography and apparent diffusion coefficient maps. Jpn J Radiol 2020; 39:66-75. [PMID: 32885378 DOI: 10.1007/s11604-020-01038-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/21/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To determine whether texture analysis of contrast-enhanced computed tomography (CECT) and apparent diffusion coefficient (ADC) maps could predict tumor grade (G1 vs G2-3) in patients with pancreatic neuroendocrine tumor (PNET). MATERIALS AND METHODS Thirty-three PNETs (22 G1 and 11 G2-3) were retrospectively reviewed. Fifty features were individually extracted from the arterial and portal venous phases of CECT and ADC maps by two radiologists. Diagnostic performance was assessed by receiver operating characteristic curves while inter-observer agreement was determined by calculating intraclass correlation coefficients (ICCs). RESULTS G2-G3 tumors were significantly larger than G1. Seventeen features significantly differed among the two readers on univariate analysis, with ICCs > 0.6; the largest area under the curve (AUC) for features of each CECT phase and ADC map was log-sigma 1.0 joint-energy = 0.855 for the arterial phase, log-sigma 1.5 kurtosis = 0.860 for the portal venous phase, and log-sigma 1.0 correlation = 0.847 for the ADC map. The log-sigma 1.5 kurtosis of the portal venous phase showed the largest AUC in the CECT and ADC map, and its sensitivity, specificity, and accuracy were 95.5%, 72.7%, and 87.9%, respectively. CONCLUSION Texture analysis may aid in differentiating between G1 and G2-3 PNET.
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Affiliation(s)
- Kazuyoshi Ohki
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
| | - Takao Igarashi
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Hirokazu Ashida
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Shinsuke Takenaga
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Megumi Shiraishi
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Yosuke Nozawa
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Hiroya Ojiri
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
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Zhao JY, Zhuang H, Luo Y, Su MG, Xiong ML, Wu YT. Double contrast-enhanced ultrasonography of a small intestinal neuroendocrine tumor: a case report of a recommendable imaging modality. PRECISION CLINICAL MEDICINE 2020; 3:147-152. [PMID: 35692609 PMCID: PMC8985797 DOI: 10.1093/pcmedi/pbaa011] [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: 02/16/2020] [Revised: 03/19/2020] [Accepted: 04/02/2020] [Indexed: 02/05/2023] Open
Abstract
A 57-year-old male presenting with spontaneously relieved abdominal cramp and distension was admitted to the West China Hospital. The diagnosis remained unclear after colonoscopy and computed tomography. Double contrast-enhanced ultrasonography was then performed and a neoplasm in the small intestine was suspected, supported by a thin-section computed tomography and positron emission tomography/computed tomography. This was confirmed pathologically after surgery to be a small intestinal G1 neuroendocrine tumor. Surgery was performed to remove approximately 25 cm of small bowel and a 3-cm solid mass located in the mesentery. The patient had a complete recovery and was tumor-free at the final follow-up. Small intestinal tumors including neuroendocrine tumors have always posed a diagnostic challenge. This case indicated that double contrast-enhanced ultrasonography is feasible in detection of small intestinal neuroendocrine tumors, and it may be an advisable approach assisting diagnosis of small intestinal tumors.
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Affiliation(s)
- Jie-Ying Zhao
- Department of Ultrasound, West China Hospital of Sichuan University, 37#Guo Xue Xiang, Chengdu, Sichuan 610041, China
| | - Hua Zhuang
- Department of Ultrasound, West China Hospital of Sichuan University, 37#Guo Xue Xiang, Chengdu, Sichuan 610041, China
| | - Yuan Luo
- Department of Ultrasound, West China Hospital of Sichuan University, 37#Guo Xue Xiang, Chengdu, Sichuan 610041, China
| | - Ming-Gang Su
- Department of Nuclear Medicine Imaging, West China Hospital of Sichuan University, 37#Guo Xue Xiang, Chengdu, Sichuan 610041, China
| | - Mo-Li Xiong
- Department of Pathology, West China Hospital of Sichuan University, 37#Guo Xue Xiang, Chengdu, Sichuan 610041, China
| | - Yu-Ting Wu
- Department of Ultrasound, West China Hospital of Sichuan University, 37#Guo Xue Xiang, Chengdu, Sichuan 610041, China
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Kamei K, Shindoh J, Kiya Y, Matsumoto I, Hashimoto M, Takeyama Y. Conversion surgery after extensive chemotherapy for stage IV mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: clinical implications from the patterns of response and recurrence. Clin J Gastroenterol 2020; 13:240-246. [PMID: 31617127 DOI: 10.1007/s12328-019-01053-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 09/28/2019] [Indexed: 02/07/2023]
Abstract
A 53-year-old woman who was diagnosed as having advanced gallbladder cancer (T3N1M1, Stage IVB) showed a dramatic response to chemotherapy using gemcitabine + cisplatin and surgery with curative intent was attempted. Histopathological examination revealed residual tumor limited to the perimuscular connective tissue of the gallbladder (T2bN0M0, Stage IIB) and a mixture of poorly differentiated adenocarcinoma and neuroendocrine carcinoma (NEC) components was confirmed. At 6 months after the surgery, a small peritoneal nodule was detected and chemotherapy was resumed with gemcitabine, cisplatin, and S-1. However, the recurrent lesion showed no response at all and gradually formed a mass with the liver and kidney. Considering the difficulty of intensive chemotherapy and the relatively indolent progression of the disease at 15 months after the recurrence was first detected, repeat resection was performed. Histopathology of the resected lesions revealed only a NEC components. Although surgical intervention may be effective in selected cases, given that the NEC component is often associated with progression and recurrence of the disease, the chemotherapy regimen would need to include drugs for the NEC component in cases where the histopathological diagnosis of MANEC has been established.
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Affiliation(s)
- Keiko Kamei
- Department of Surgery, Kindai University, Osaka, Japan
| | - Junichi Shindoh
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Yoshitaka Kiya
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan
| | | | - Masaji Hashimoto
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan
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Christ E, Antwi K, Fani M, Wild D. Innovative imaging of insulinoma: the end of sampling? A review. Endocr Relat Cancer 2020; 27:R79-R92. [PMID: 31951592 PMCID: PMC7040495 DOI: 10.1530/erc-19-0476] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Accepted: 01/17/2020] [Indexed: 12/16/2022]
Abstract
Receptors for the incretin glucagon-like peptide-1 (GLP-1R) have been found overexpressed in selected types of human tumors and may, therefore, play an increasingly important role in endocrine gastrointestinal tumor management. In particular, virtually all benign insulinomas express GLP-1R in high density. Targeting GLP-1R with indium-111, technetium-99m or gallium-68-labeled exendin-4 offers a new approach that permits the successful localization of small benign insulinomas. It is likely that this new non-invasive technique has the potential to replace the invasive localization of insulinomas by selective arterial stimulation and venous sampling. In contrast to benign insulinomas, malignant insulin-secreting neuroendocrine tumors express GLP-1R in only one-third of the cases, while they more often express the somatostatin subtype 2 receptors. Importantly, one of the two receptors appears to be always overexpressed. In special cases of endogenous hyperinsulinemic hypoglycemia (EHH), that is, in the context of MEN-1 or adult nesidioblastosis GLP-1R imaging is useful whereas in postprandial hypoglycemia in the context of bariatric surgery, GLP-1R imaging is probably not helpful. This review focuses on the potential use of GLP-1R imaging in the differential diagnosis of EHH.
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Affiliation(s)
- Emanuel Christ
- Division of Endocrinology, Diabetology and Metabolism, University Hospital of Basel, University of Basel, Basel, Switzerland
- Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel Switzerland
| | - Kwadwo Antwi
- Clinic of Radiology and Nuclear Medicine, University Hospital, Basel, Switzerland
| | - Melpomeni Fani
- Clinic of Radiology and Nuclear Medicine, University Hospital, Basel, Switzerland
| | - Damian Wild
- Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel Switzerland
- Clinic of Radiology and Nuclear Medicine, University Hospital, Basel, Switzerland
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Lu J, Zhao YJ, Zhou Y, He Q, Tian Y, Hao H, Qiu X, Jiang L, Zhao G, Huang CM. Modified staging system for gastric neuroendocrine carcinoma based on American Joint Committee on Cancer and European Neuroendocrine Tumor Society systems. Br J Surg 2020; 107:248-257. [PMID: 31971627 DOI: 10.1002/bjs.11408] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/04/2019] [Accepted: 10/01/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognostic values of the AJCC staging system for gastric cancer (GC-AJCC), the AJCC staging system for gastric neuroendocrine tumours (NET-AJCC) and the European Neuroendocrine Tumor Society (ENETS) system for gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma (MA)NEC remain controversial. METHODS Data on patients with (MA)NEC from 21 centres in China were analysed. Different staging systems were evaluated by performing Kaplan-Meier survival analysis and calculating the concordance index (C-index) and Akaike information criterion (AIC). Based on three existing systems, a modified staging system (mTNM) was developed. RESULTS A total of 871 patients were included. In the GC-AJCC system, an overlap was noticed for pT2 and pT3 categories. Patients with stage IIIC disease had a similar prognosis to those with stage IV disease. The pT categories of the NET-AJCC system had a lower C-index and higher AIC than those of the other systems. In the ENETS system, there was a low proportion (0·2 per cent) of patients with stage IIIA and a high proportion (67·6 per cent) of stage IIIB disease. The mTNM system adopted the NET-AJCC pT and GC-AJCC pN and pM definitions, and was developed based on the ENETS stage definitions. The proportion of patients in each stage was better distributed and the mTNM system showed improved prognostic performance in predicting overall and disease-free survival. CONCLUSION The mTNM system offers more accurate prognostic value for gastric (MA)NEC than the AJCC or ENETS staging systems.
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Affiliation(s)
- J Lu
- Departments of Gastric Surgery
- General Surgery, Fujian Medical University Union Hospital
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer
- Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University
| | - Y J Zhao
- Department of Gastrointestinal Surgery, West District of the First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei
| | - Y Zhou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao
| | - Q He
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou
| | - Y Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
| | - H Hao
- Department of General Surgery, Huashan Hospital, Fudan University
| | - X Qiu
- Department of Gastrointestinal Surgery and Gastrointestinal Surgery Research Institute, Affiliated Hospital of Putian University, Putian
| | - L Jiang
- Department of Gastrointestinal Surgery, Yan Tai Yu Huang Ding Hospital, Yantai, China
| | - G Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiaotong University, Shanghai
| | - C-M Huang
- Departments of Gastric Surgery
- General Surgery, Fujian Medical University Union Hospital
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer
- Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University
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Shi H, Chen L, Zhang Q, Lin Y, Jiang C, Yao H, Hou X, Chen M, Lin R, Chen J. Concordance Between the Ki-67 Index Cutoff Value of 55% and Differentiation in Neuroendocrine Tumor and Neuroendocrine Carcinoma in Grade 3 Pancreatic Neuroendocrine Neoplasms. Pancreas 2020; 49:1378-1382. [PMID: 33122528 DOI: 10.1097/mpa.0000000000001693] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE In 2017 and 2019, the World Health Organization defined grade 3 neuroendocrine tumors (G3 NETs) and neuroendocrine carcinoma (G3 NEC) in the pancreas. The validity of this classification remains to be verified. METHODS Clinical data were collected and analyzed for 39 G3 pancreatic neuroendocrine neoplasms (PanNENs) patients between 2009 and 2018. RESULTS The tumor-node-metastasis stage (P = 0.0260), differentiation (P = 0.0115), and Ki-67 index (P = 0.0371) are prognostic factors for G3 PanNENs by Kaplan-Meier survival analysis. Among 39 patients, 18 had a Ki-67 index of less than 55% and well-differentiated morphology (G3 NET) and 16 had a Ki-67 index of 55% or greater and poorly differentiated morphology (G3 NEC). Grade 3 neuroendocrine tumor had a significant better prognosis than G3 NEC (median overall survival time, 25 months [95% confidence interval, 10.854-39.146 months] vs 12 months [95% confidence interval, 6.316-17.684 months], P = 0.0164). Based on Cox regression analyses, tumor-node-metastasis stage (P = 0.016) was identified as the independent prognostic factor for G3 PanNENs. CONCLUSIONS The upper Ki-67 index cutoff of 55% might be the best cutoff value to define G3 NETs and G3 NECs for G3 PanNENs. The World Health Organization 2017 and 2019 classification system for G3 PanNENs can identify high-risk patients with G3 PanNENs.
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Affiliation(s)
- Huiying Shi
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Luohai Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou
| | - Qin Zhang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Yuan Lin
- Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chen Jiang
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Hailing Yao
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Xiaohua Hou
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Minhu Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou
| | - Rong Lin
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Jie Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou
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Okuyama H, Ikeda M, Okusaka T, Furukawa M, Ohkawa S, Hosokawa A, Kojima Y, Hara H, Murohisa G, Shioji K, Asagi A, Mizuno N, Kojima M, Yamanaka T, Furuse J. A Phase II Trial of Everolimus in Patients with Advanced Pancreatic Neuroendocrine Carcinoma Refractory or Intolerant to Platinum-Containing Chemotherapy (NECTOR Trial). Neuroendocrinology 2020; 110:988-993. [PMID: 31986515 DOI: 10.1159/000505550] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 12/18/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND Platinum-containing regimens are widely used as first-line chemotherapy for unresectable pancreatic neuroendocrine carcinoma (NEC), but second-line chemotherapies have yet to be established. OBJECTIVES We evaluated the safety and efficacy of everolimus in patients with pancreatic NEC refractory or intolerant to platinum-containing chemotherapy. METHODS This study was a prospective, multicenter, phase II trial in patients with pancreatic NEC after platinum-containing chemotherapy. Everolimus treatment was continued until disease progression or intolerable toxicity was observed. The primary endpoint was progression-free survival (PFS). RESULTS Participants comprised 25 patients. Median age was 63 years, median PFS was 1.2 months (95% confidence interval [CI] 0.9-3.1 months), median overall survival was 7.5 months (95% CI 3.1-13.5 months), overall response rate was 0%, and disease control rate was 39.1%. Common grade 3/4 adverse events were hyperglycemia (20%), thrombocytopenia (16%), and anemia (16%). CONCLUSION The efficacy of everolimus was limited in patients with unresectable pancreatic NEC.
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Affiliation(s)
- Hiroyuki Okuyama
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan,
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Masayuki Furukawa
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Shinichi Ohkawa
- Division of Hepatobiliary and Pancreatic Oncology, Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Ayumu Hosokawa
- Department of Gastroenterology and Hematology, Faculty of Medicine University of Toyama, Toyama, Japan
| | - Yasushi Kojima
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroki Hara
- Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan
| | - Gou Murohisa
- Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan
| | - Kazuhiko Shioji
- Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan
| | - Akinori Asagi
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Motohiro Kojima
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Takeharu Yamanaka
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan
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Velikyan I, Eriksson O. Advances in GLP-1 receptor targeting radiolabeled agent development and prospective of theranostics. Theranostics 2020; 10:437-461. [PMID: 31903131 PMCID: PMC6929622 DOI: 10.7150/thno.38366] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 09/10/2019] [Indexed: 12/15/2022] Open
Abstract
In the light of theranostics/radiotheranostics and prospective of personalized medicine in diabetes and oncology, this review presents prior and current advances in the development of radiolabeled imaging and radiotherapeutic exendin-based agents targeting glucagon-like peptide-1 receptor. The review covers chemistry, preclinical, and clinical evaluation. Such critical aspects as structure-activity-relationship, stability, physiological potency, kidney uptake, and dosimetry are discussed.
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Affiliation(s)
- Irina Velikyan
- Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
| | - Olof Eriksson
- Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
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Lepage C. Épidémiologie des tumeurs neuroendocrines intestinales. ONCOLOGIE 2020. [DOI: 10.3166/onco-2019-0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Les données disponibles concernant l’incidence et les facteurs pronostiques des tumeurs neuroendocrines (TNE) digestives sont souvent fragmentaires. Les TNE digestives sont rares et représentent environ 1 % des cancers digestifs. En France, l’incidence des TNE digestives malignes est estimée à 1,1/100 000 chez l’homme et à 0,9/100 000 chez la femme. L’incidence augmente au cours du temps. Du fait de leur longue survie, les TNE constituent, après le cancer colorectal, le cancer digestif dont la prévalence est la plus élevée. La plupart des TNE sont bien différenciées, les carcinomes neuroendocrines peu différenciés représentent moins de 20 % des TNE digestives. Parmi les TNE bien différenciées intestinales, les localisations les plus fréquentes sont l’intestin grêle et le colorectal. Plus de la moitié des TNE sont diagnostiquées au stade métastatique, principalement au niveau hépatique. Le degré de différenciation, le grade histologique, la localisation du primitif et le stade sont les principaux facteurs pronostiques. Les taux de survie relative à cinq ans étaient de 4,5 % pour les tumeurs peu différenciées versus plus de 55 % pour les TNE bien différenciées.
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Crown A, Rocha FG, Raghu P, Lin B, Funk G, Alseidi A, Hubka M, Rosales J, Lee M, Kennecke H. Impact of initial imaging with gallium‐68 dotatate PET/CT on diagnosis and management of patients with neuroendocrine tumors. J Surg Oncol 2019; 121:480-485. [DOI: 10.1002/jso.25812] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 12/01/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Angelena Crown
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Flavio G. Rocha
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Preethi Raghu
- Department of RadiologyVirginia Mason Medical CenterSeattle WA
| | - Bruce Lin
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
| | - Gayle Funk
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
| | - Adnan Alseidi
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Misho Hubka
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Joseph Rosales
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
| | - Marie Lee
- Department of RadiologyVirginia Mason Medical CenterSeattle WA
| | - Hagen Kennecke
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
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Saadeh H, Abdullah N, Erashdi M, Sughayer M, Al-Kadi O. Histopathologist-level quantification of Ki-67 immunoexpression in gastroenteropancreatic neuroendocrine tumors using semiautomated method. J Med Imaging (Bellingham) 2019; 7:012704. [PMID: 31824983 DOI: 10.1117/1.jmi.7.1.012704] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 11/18/2019] [Indexed: 11/14/2022] Open
Abstract
The role of Ki-67 index in determining the prognosis and management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has become more important yet presents a challenging assessment dilemma. Although the precise method of Ki-67 index evaluation has not been standardized, several methods have been proposed, and each has its pros and cons. Our study proposes an imaging semiautomated informatics framework [semiautomated counting (SAC)] using the popular biomedical imaging tool "ImageJ" to quantify Ki-67 index of the GEP-NETs using camera-captured images of tumor hotspots. It aims to assist pathologists in achieving an accurate and rapid interpretation of Ki-67 index and better reproducibility of the results with minimal human interaction and calibration. Twenty cases of resected GEP-NETs with Ki-67 staining that had been done for diagnostic purposes have been randomly selected from the pathology archive. All of these cases were reviewed in a multidisciplinary cancer center between 2012 and 2019. For each case, the Ki-67 immunostained slide was evaluated and five camera-captured images at 40 × magnification were taken. Prints of images were used by three pathologists to manually count the tumor cells. The digital versions of the images were used for the semiautomated cell counting using ImageJ. Statistical analysis of the Ki-67 index correlation between the proposed method and the MC revealed strong agreement on all the cases evaluates ( n = 20 ), with an intraclass correlation coefficient of 0.993, "95% CI: 0.984 to 0.997." The results obtained from the SAC are promising and demonstrate the capability of this methodology for the development of reproducible and accurate semiautomated quantitative pathological assessments. ImageJ features are investigated carefully and accurately fine-tuned to obtain the optimal sequence of steps that will accurately calculate Ki-67 index. SAC is able to accurately grade all the cases evaluated perfectly mating histopathologists' manual grading, providing reliable and efficient solution for Ki-67 index assessment.
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Affiliation(s)
- Heba Saadeh
- The University of Jordan, King Abdullah II School for IT, Computer Science Department, Amman, Jordan
| | - Niveen Abdullah
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Al-Jubeiha, Amman, Jordan
| | - Madiha Erashdi
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Al-Jubeiha, Amman, Jordan
| | - Maher Sughayer
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Al-Jubeiha, Amman, Jordan
| | - Omar Al-Kadi
- The University of Jordan, King Abdullah II School for IT, Information Technology Department, Amman, Jordan
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Singh A, Hines JJ, Friedman B. Multimodality Imaging of the Pancreatic Neuroendocrine Tumors. Semin Ultrasound CT MR 2019; 40:469-482. [DOI: 10.1053/j.sult.2019.04.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Lee L, Ramos-Alvarez I, Ito T, Jensen RT. Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. Int J Mol Sci 2019; 20:5128. [PMID: 31623145 PMCID: PMC6829234 DOI: 10.3390/ijms20205128] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/08/2019] [Accepted: 10/13/2019] [Indexed: 02/07/2023] Open
Abstract
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
| | | | - Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan.
| | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
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Abstract
Neuroendocrine tumors (NETs) originate from the neuroendocrine cell system in the bronchial and gastrointestinal tract and can produce hormones leading to distinct clinical syndromes. Systemic treatment of patients with unresectable NETs aims to control symptoms related to hormonal overproduction and tumor growth. In the last decades prognosis has improved as a result of increased detection of early stage disease and the introduction of somatostatin analogs (SSAs) as well as several new therapeutic options. SSAs are the first-line medical treatment of NETs and can control hormonal production and tumor growth. The development of next-generation multireceptor targeted and radiolabelled somatostatin analogs, as well as target-directed therapies (as second-line treatment options) further improve progression-free survival in NET patients. To date, however, a significant prolongation of overall survival with systemic treatment in NET has not been convincingly demonstrated. Several new medical options and treatment combinations will become available in the upcoming years, and although preliminary results of preclinical and clinical trials are encouraging, large, preferrably randomized clinical studies are required to provide definitive evidence of their effect on survival and symptom control.
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Luo Y, Chen X, Chen J, Song C, Shen J, Xiao H, Chen M, Li ZP, Huang B, Feng ST. Preoperative Prediction of Pancreatic Neuroendocrine Neoplasms Grading Based on Enhanced Computed Tomography Imaging: Validation of Deep Learning with a Convolutional Neural Network. Neuroendocrinology 2019; 110:338-350. [PMID: 31525737 DOI: 10.1159/000503291] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The pathological grading of pancreatic neuroendocrine neoplasms (pNENs) is an independent predictor of survival and indicator for treatment. Deep learning (DL) with a convolutional neural network (CNN) may improve the preoperative prediction of pNEN grading. METHODS Ninety-three pNEN patients with preoperative contrast-enhanced computed tomography (CECT) from Hospital I were retrospectively enrolled. A CNN-based DL algorithm was applied to the CECT images to obtain 3 models (arterial, venous, and arterial/venous models), the performances of which were evaluated via an eightfold cross-validation technique. The CECT images of the optimal phase were used for comparing the DL and traditional machine learning (TML) models in predicting the pathological grading of pNENs. The performance of radiologists by using qualitative and quantitative computed tomography findings was also evaluated. The best DL model from the eightfold cross-validation was evaluated on an independent testing set of 19 patients from Hospital II who were scanned on a different scanner. The Kaplan-Meier (KM) analysis was employed for survival analysis. RESULTS The area under the curve (AUC; 0.81) of arterial phase in validation set was significantly higher than those of venous (AUC 0.57, p = 0.03) and arterial/venous phase (AUC 0.70, p = 0.03) in predicting the pathological grading of pNENs. Compared with the TML models, the DL model gave a higher (although insignificantly) AUC. The highest OR was achieved for the p ratio <0.9, the AUC and accuracy for diagnosing G3 pNENs were 0.80 and 79.1% respectively. The DL algorithm achieved an AUC of 0.82 and an accuracy of 88.1% for the independent testing set. The KM analysis showed a statistical significant difference between the predicted G1/2 and G3 groups in the progression-free survival (p = 0.001) and overall survival (p < 0.001). CONCLUSION The CNN-based DL method showed a relatively robust performance in predicting pathological grading of pNENs from CECT images.
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Affiliation(s)
- Yanji Luo
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xin Chen
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Block A2, Xili Campus of Shenzhen University, Shenzhen, China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chenyu Song
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jingxian Shen
- Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Huanhui Xiao
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Block A2, Xili Campus of Shenzhen University, Shenzhen, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bingsheng Huang
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Block A2, Xili Campus of Shenzhen University, Shenzhen, China,
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Kooyker AI, Verbeek WH, van den Berg JG, Tesselaar ME, van Leerdam ME. Change in incidence, characteristics and management of colorectal neuroendocrine tumours in the Netherlands in the last decade. United European Gastroenterol J 2019; 8:59-67. [PMID: 32213058 PMCID: PMC7006007 DOI: 10.1177/2050640619865113] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are rare. However, a rising incidence has been reported over the past decades. For colorectal NETs, this is presumably caused by an increased awareness of colorectal diseases and colonoscopic procedures. This study aims to analyse the change in incidence of colorectal NETs, characteristics and management and evaluate the proportion of colorectal NETs detected in a national colorectal cancer (CRC) screening programme. METHODS Histopathological reports on colorectal well-differentiated NETs detected between 2006 and 2016 were collected from the Dutch pathology database (PALGA) containing nationwide histo- and cytopathology reports of all pathology laboratories in the Netherlands. RESULTS Colorectal NETs were detected in 1055 individuals. Increasing incidence rates were observed from 0.36 per 100,000 inhabitants in 2006 to 0.75 per 100,000 inhabitants in 2011 (p value < 0.001), remaining stable afterward. Most NETs were grade I (73.5%) and detected in the rectum (76.4%). The majority (88.2%) were detected by colonoscopy, and the final intervention depended significantly on primary location of the tumour; 94.6% of rectal NETs were endoscopically removed, whereas 61.0% of colonic NETs were removed by surgery. There was an increase in local excision both of rectal and colonic NETs over the years instead of radical resection. Screening for CRC started in 2014 and contributed by detecting 32% of the diagnosed colorectal NETs within the invited age group, of which 94.6% were detected at an early stage. CONCLUSION The incidence of reported colorectal NETs in the Netherlands doubled over the last decade. The Dutch CRC screening programme had a clear contribution to colorectal NETs incidence among its target population. A shift to more local management of detected lesions was observed over time.
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Affiliation(s)
- Arthur I Kooyker
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Wieke Hm Verbeek
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - José G van den Berg
- Department of Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Margot Et Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
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Differentiation between non-hypervascular pancreatic neuroendocrine tumour and pancreatic ductal adenocarcinoma on dynamic computed tomography and non-enhanced magnetic resonance imaging. Pol J Radiol 2019; 84:e153-e161. [PMID: 31019610 PMCID: PMC6479137 DOI: 10.5114/pjr.2019.84193] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 02/11/2019] [Indexed: 12/30/2022] Open
Abstract
Purpose To determine the differentiating features between non-hypervascular pancreatic neuroendocrine tumour (PNET) and pancreatic ductal adenocarcinoma (PDAC) on dynamic computed tomography (CT) and non-enhanced magnetic resonance imaging (MRI). Material and methods We enrolled 102 patients with non-hypervascular PNET (n = 15) or PDAC (n = 87), who had undergone dynamic CT and non-enhanced MRI. One radiologist evaluated all images, and the results were subjected to univariate and multivariate analyses. To investigate reproducibility, a second radiologist re-evaluated features that were significantly different between PNET and PDAC on multivariate analysis. Results Tumour margin (well-defined or ill-defined) and enhancement ratio of tumour (ERT) showed significant differences in univariate and multivariate analyses. Multivariate analysis revealed a predominance of well-defined tumour margins in non-hypervascular PNET, with an odds ratio of 168.86 (95% confidence interval [CI]: 10.62-2685.29; p < 0.001). Furthermore, ERT was significantly lower in non-hypervascular PNET than in PDAC, with an odds ratio of 85.80 (95% CI: 2.57-2860.95; p = 0.01). Sensitivity, specificity, and accuracy were 86.7%, 96.6%, and 95.1%, respectively, when the tumour margin was used as the criteria. The values for ERT were 66.7%, 98.9%, and 94.1%, respectively. In reproducibility tests, both tumour margin and ERT showed substantial agreement (margin of tumour, κ = 0.6356; ERT, intraclass correlation coefficients (ICC) = 0.6155). Conclusions Non-hypervascular PNET showed well-defined margins and lower ERT compared to PDAC, with significant differences. Our results showed that non-hypervascular PNET can be differentiated from PDAC via dynamic CT and non-enhanced MRI.
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The Influence of Tumor Stage on the Prognostic Value of Ki-67 Index and Mitotic Count in Small Intestinal Neuroendocrine Tumors. Am J Surg Pathol 2019; 42:247-255. [PMID: 29016403 DOI: 10.1097/pas.0000000000000968] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Tumor cell proliferation rate determined by either Ki-67 index or mitotic count (MC) has shown to be a prognostic factor for gastrointestinal neuroendocrine tumors in general, and after its incorporation in the 2010 World Health Organization tumor grading system, it has become essentially mandatory in pathology reports for all gastrointestinal neuroendocrine tumors, regardless of tumor location. Nevertheless, clinical significance for the Ki-67 index or MC has not been well demonstrated in small intestinal neuroendocrine tumor (SINET), especially those without distant metastasis, the majority of which have very low proliferation rates. We assessed the clinical behavior of 130 SINETs in relation to stage, Ki-67 index, MC, and other pathologic features. Most SINETs (86%) were grade 1 and 14% were grade 2. There were no grade 3 tumors or poorly differentiated neuroendocrine carcinomas. On multivariate analysis, age, Ki-67 index >5%, MC >10/50 high-power field, stage IV, and liver metastases were associated with increased risk of death in all patients. When both stage and grade were considered, Ki-67 index >5% was associated with a nearly 4-fold increased risk of death in stage IV cases (n=60). In contrast, Ki-67 index did not show prognostic value for patients with stages I to III disease (n=70), although MC >1/50 high-power field was significantly associated with death on multivariable analysis. Our study confirms that liver metastasis and increased tumor cell proliferation rate are independent prognostic factors for SINETs, but shows that most SINETs have a very low proliferation rate, which limits its value for predicting tumor behavior. By combining staging and grading information, we demonstrate different roles and cutoff values of Ki-67 index and MC in SINET with different stages.
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Zhang C, Huang Y, Long J, Yao X, Wang J, Zang S, Qu W, Wang F. Serum chromogranin A for the diagnosis of gastroenteropancreatic neuroendocrine neoplasms and its association with tumour expression. Oncol Lett 2019; 17:1497-1504. [PMID: 30675205 PMCID: PMC6341841 DOI: 10.3892/ol.2018.9795] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 10/03/2018] [Indexed: 01/26/2023] Open
Abstract
The aim of the present study was to assess the clinical value of serum chromogranin A (CgA) levels in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and to compare them with tumour expression of CgA. A total of 109 consecutive patients with confirmed GEP-NENs were enrolled in this prospective study between December 2012 and August 2016, including 73 patients with primary or recurrent GEP-NENs and 36 patients with GEP-NENs that were treated following surgery. Furthermore, 30 patients with benign gastrointestinal diseases and 30 healthy volunteers served as control groups. Serum CgA levels were measured by ELISA, using different reference values, in order to evaluate its diagnostic efficacy. Serum neuron-specific enolase was also measured to evaluate its diagnostic efficacy and analyse its association with serum CgA levels. The levels of CgA, synaptophysin and neural cell adhesion molecule 1 in the tumour tissue were assessed by immunohistochemical assays. The results indicated that serum CgA levels were significantly higher in patients with GEP-NENs compared with the control groups (P<0.05). No association was observed between serum CgA levels and tumour grade (G1, G2 and G3), but serum CgA levels differed significantly between patients with GEP-NENs of different origins (P<0.05). A serum CgA cut-off value of 85.3 ng/ml was associated with high sensitivity (64.4%) and specificity (92.7%). Different reference values were recommended for NENs of different origins, with serum CgA cut-off values of 96.72, 51.13 and 86.19 ng/ml for the stomach, intestines and pancreas, respectively. The serum CgA levels were consistent with the CgA expression in the tumour. In conclusion, serum CgA may serve as a circulating pathological biomarker for the diagnosis of GEP-NENs. The use of different reference values for different tumour origins may improve the diagnostic efficacy of CgA for GEP-NENs. A cut-off value of 85.3 ng/ml is recommended in the Chinese population.
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Affiliation(s)
- Chuan Zhang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Yue Huang
- Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Jiang Long
- Department of Pancreas Surgery, Fudan University Shanghai Cancer Centre, Shanghai 200032, P.R. China
| | - Xiaochen Yao
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Jun Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Shimin Zang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Wei Qu
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Feng Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
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Viknesh M, Bin Hisham F, Sankaran P, Kong Choon S, Azim Bin Nik Abdullah N. Bleeding and malignant pancreatic neuroendocrine neoplasms: A Malaysian case series. INTERNATIONAL JOURNAL OF HEPATOBILIARY AND PANCREATIC DISEASES 2019. [DOI: 10.5348/100084z04mv2019cs] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Al Bulushi N, Al Suqri B, Al Aamri M, Al Hadidi A, Al Jahdami H, Al Zadjali M, Al Risi M. Diagnostic accuracy of technetium-99m-octreotide in imaging neuroendocrine tumors, Oman hospital experience with literature review. World J Nucl Med 2019; 18:137-142. [PMID: 31040744 PMCID: PMC6476243 DOI: 10.4103/wjnm.wjnm_36_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The aim of this observational cross-sectional study with retrospective review of the data is to evaluate the efficacy of using technetium-99m-octreotide (Tc-99m-OCT) in imaging neuroendocrine tumors (NETs) in our tertiary care hospital. A total of 58 patients had Tc-99m-OCT were identified in our database, from January 2013 to December 2016. Forty-one patients (age range of 15–75 years) meet our inclusion criteria, namely histopathology proven NETs, Tc-99m-OCT scan, computed tomography (CT), or magnetic resonance imaging (MRI) done in our institute for correlation. Twenty-three patients had true positive Tc-99m-OCT scan. In addition to the primary tumors, the octreotide scan revealed metastasis in the lung, liver, and retroperitoneal lymph nodes. The smallest lesion detected on octreotide scan was a 4-mm pulmonary nodule that was missed on lung window CT scan. The Tc-99m-OCT had 17 true negative, one false negative, and no false positive. The CT and MRI scans had 18 true positive, 17 true negative, 5 false negative, and one false positive. The overall sensitivity, specificity, accuracy, positive, and negative predictive values of Tc-99m-OCT scan were 96%, 100%, 97%, 100%, and 94%, respectively. Whereas those of CT and MRI were 78%, 94%, 85%, 94%, and 77%, respectively. Our diagnostic accuracy of Tc-99m-OCT is high. We recommend that, in addition to the conventional radiological investigations, Tc-99m-OCT scan, or other somatostatin receptor imaging (SSR) is a mandate for better and accurate staging of patients with NETs.
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Affiliation(s)
- Naima Al Bulushi
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
| | - Badriya Al Suqri
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
| | - Marwa Al Aamri
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
| | | | - Hafidh Al Jahdami
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
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Wrzesień M, Albiniak Ł. 68Ga-DOTA-TATE-a source of eye lens exposure for nuclear medicine department workers. JOURNAL OF RADIOLOGICAL PROTECTION : OFFICIAL JOURNAL OF THE SOCIETY FOR RADIOLOGICAL PROTECTION 2018; 38:1512-1523. [PMID: 30468680 DOI: 10.1088/1361-6498/aaea8e] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Obtaining 68Ga-DOTA-TATE (a radioconjugate consisting of the somatostatin analogue tyrosine-3-octreotate (Tyr3-octreotate or TATE) labelled with the positron emission tomography tracer gallium 68Ga via the macrocyclic chelating agent dodecanetetraacetic acid (DOTA)) is a complex process and, as with any radiopharmaceutical whose basis is a short-lived radionuclide generator, it is based on a sequence of procedures beginning from the 68Ge/68Ga generator elution, labelling ligands with a radioisotope, dispensing doses of 68Ga-DOTA-TATE for patients and finally injection of the preparation to patients. The complexity of this process may contribute to an increased exposure of eye lenses of the staff who perform the above-mentioned procedures, which is especially important at a time when the dose limit on the lens of the eye is being reduced from 150 to 20 mSv yr-1. OBJECTIVE The work presents the exposure of eye lenses of the personnel of a nuclear medicine department who prepare and inject 68Ga-DOTA-TATE. MATERIALS AND METHODS Radiochemists and nurses were monitored by dosimetry measurements with thermoluminescent detectors (TLDs). RESULTS The values of Hp(3)/A-normalised personal eye dose equivalent recorded in the group of radiochemists during the procedure of dispensing the doses of 68Ga-DOTA-TATE for patients exceeded the value of 274 μSv/GBq. CONCLUSIONS The estimated annual Hp(3) values may exceed 20 mSv, which is particularly important due to the fact that procedures using the 68Ga radioactivity are only a small part of the daily professional activity of the staff, resulting from the performance of other procedures that require the use of other radioisotopes.
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Xie JW, Li P, Wang JB, Lin JX, Lu J, Chen QY, Yang YH, Kang DY, Zheng CH, Huang CM. Modified AJCC staging of gastric neuroendocrine carcinoma based on T staging can improve the capacity of prognosis assessment. J Cancer Res Clin Oncol 2018; 144:2391-2397. [PMID: 30209612 DOI: 10.1007/s00432-018-2750-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 09/08/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND OR PURPOSE This study was designed to determine the value of AJCC staging 7th edition and improved AJCC staging in assessing the prognosis of gastric neuroendocrine carcinoma (GNEC). METHODS In total, GNEC 475 patients in the Surveillance, Epidemiology, and End Results (SEER) database and 129 GNEC patients in our department undergoing resection were included. The former served as the test group, and the latter served as the validation group. Those with stage IIIb disease were allocated into four subgroups, and improved AJCC staging was established. The AIC and C indices were used to evaluate the capacities of different TNM staging. RESULTS Significant overlap between stages IIIb and IIIa in both the test and validation groups was found. In the test group, T staging and age at disease diagnosis were independent prognostic factors for patients with stage IIIb. Stage IIIb was divided into T1N1, T2N1, T3N1 and T4N1, and the improved AJCC staging-mTNM staging was created. In mTNM staging, the IIIb survival curve did not cross those of stages IIIa and IIb, which had a smaller AIC (2490 vs. 2507) value and larger C index (0.7624 vs. 0.7450, P = 0.228). Similar results were obtained for the validation group. CONCLUSION T stage was an independent factor influencing the prognosis of stage IIIb GNEC patients, and the improved AJCC staging proposed here has good prognostic value.
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Affiliation(s)
- Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ying-Hong Yang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China
| | - De-Yong Kang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
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