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Pitman MB. The World Health Organization Reporting System for Pancreaticobiliary Cytopathology: Review and Comparison to the Papanicolaou Society of Cytopathology System. Arch Pathol Lab Med 2025; 149:e39-e46. [PMID: 38190275 DOI: 10.5858/arpa.2023-0411-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2023] [Indexed: 01/10/2024]
Abstract
CONTEXT.— The World Health Organization (WHO) Reporting System for Pancreaticobiliary Cytopathology (WHO System) is the product of a joint venture between the World Health Organization, the International Academy of Cytology, and the International Agency for Research on Cancer. The WHO System revises the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System) and replaces the 6-tiered system with a 7-tiered system. OBJECTIVE.— To explain the WHO System and the differences with the PSC System. DATA SOURCES.— The WHO System and the PSC System of Reporting Pancreaticobiliary Cytopathology. CONCLUSIONS.— The diagnostic categories of the WHO System are "Insufficient/Inadequate/Nondiagnostic"; "Benign (Negative for Malignancy)"; "Atypical"; "Pancreaticobiliary Neoplasm, Low Risk/Low Grade (PaN-Low)"; "Pancreatic Neoplasm, High Risk/High Grade (PaN-High)"; "Suspicious for Malignancy"; and "Malignant." In the WHO System, the "benign" category includes both nonneoplastic and neoplastic lesions, so the "Neoplastic: Benign" category of the PSC system has been eliminated. Low-grade malignancies, pancreatic neuroendocrine tumors (PanNETs), and solid-pseudopapillary neoplasm (SPN) classified as "Neoplastic: Other" in the PSC System are classified as "Malignant" in the WHO System, leaving in the "Neoplasm" category intraductal lesions, which are divided into 2 new diagnostic categories: "Pancreaticobiliary Neoplasm (PaN)-Low Risk/Grade" and "PaN-High Risk/Grade." As with the PSC System, the WHO System advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (carcinoembryonic antigen [CEA] and amylase) and molecular testing. The WHO System includes risk of malignancy per category, and reporting and diagnostic management options that recognize the variations in resources of low- and middle-income countries.
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Affiliation(s)
- Martha B Pitman
- From the Department of Pathology, Harvard Medical School, Boston, Massachusetts; and the Department of Pathology, Massachusetts General Hospital, Boston
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López Gonzalez M, Hernando-Requejo O, Ciervide Jurío R, Montero Luis Á, Saiz Guisasola C, Sánchez Saugar E, Álvarez Rodríguez B, Chen-Zhao X, García-Aranda M, Valero Albarran J, Alonso Gutierrez R, García Cañamaque L, Prados S, Quijano Y, de Vicente E, Rubio C. Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis. Clin Transl Oncol 2025; 27:377-385. [PMID: 38907097 DOI: 10.1007/s12094-024-03538-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/24/2024] [Indexed: 06/23/2024]
Abstract
INTRODUCTION Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.
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Affiliation(s)
- Mercedes López Gonzalez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain.
| | - Ovidio Hernando-Requejo
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Raquel Ciervide Jurío
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Ángel Montero Luis
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Carmen Saiz Guisasola
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Emilio Sánchez Saugar
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Beatriz Álvarez Rodríguez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Xin Chen-Zhao
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Mariola García-Aranda
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Jeannette Valero Albarran
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Rosa Alonso Gutierrez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Lina García Cañamaque
- Department of Nuclear Medicine, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Susana Prados
- Department of Gastroenterology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Yolanda Quijano
- Department of Surgery, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Emilio de Vicente
- Department of Surgery, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Carmen Rubio
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
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Sultan M, Al Hasan A, Khazem N. Liver metastasized pancreatic neuroendocrine tumor in a 17-year-old female: A case report. Clin Case Rep 2024; 12:e9545. [PMID: 39502124 PMCID: PMC11534639 DOI: 10.1002/ccr3.9545] [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: 10/13/2023] [Revised: 09/13/2024] [Accepted: 10/03/2024] [Indexed: 11/08/2024] Open
Abstract
Key Clinical Message Pancreatic neuroendocrine tumors (PNETs) are rare and often misdiagnosed due to their vague symptoms and tumor heterogeneity. Early detection using computed tomography (CT) is essential, particularly in regions without access to advanced diagnostic tools like immunohistochemistry and genetic testing. Abstract Neuroendocrine tumors (NETs) are rare tumors in adults and extremely rare in the pediatric population, as pancreatic NETs (pNETs) have an incidence rate of <0.1 per million. We present a case of a 17-year-old female with a liver metastasized pNET. A 17-year-old female with a history of intermittent abdomen-back pain presented to the clinic with severe upper abdominal pain radiating to the shoulder. The routine tests were normal. An ultrasound showed multiple lesions in the liver, which were confirmed by a computed tomography (CT) that uncovered a pancreatic lesion too. A liver biopsy proved it was a metastasized pNET with positive NET markers on IMC staining. The metaiodobenzylguanidine (MIBG) scan flared the liver lesion. The patient was started on Octreotide long-acting release (LAR) 30 mg once monthly. The rarity of these tumors makes their diagnosis difficult, but they should not be omitted and must be considered when there are long-lasting symptoms that are not compatible with common illnesses. These tumors are curable in their early stages.
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Ahmed TM, Zhu Z, Yasrab M, Blanco A, Kawamoto S, He J, Fishman EK, Chu L, Javed AA. Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model. Ann Surg Oncol 2024; 31:8136-8145. [PMID: 39179862 DOI: 10.1245/s10434-024-16064-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/04/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2 cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). PATIENTS AND METHODS An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. RESULTS Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2 cm). CONCLUSIONS Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.
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Affiliation(s)
- Taha M Ahmed
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Zhuotun Zhu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Mohammad Yasrab
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Alejandra Blanco
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Satomi Kawamoto
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K Fishman
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Linda Chu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Ammar A Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, NYU Langone Grossman School of Medicine, New York, NY, USA.
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Mapelli P, Bezzi C, Muffatti F, Ghezzo S, Canevari C, Magnani P, Schiavo Lena M, Battistella A, Scifo P, Andreasi V, Partelli S, Chiti A, Falconi M, Picchio M. Preoperative assessment of lymph nodal metastases with [ 68Ga]Ga-DOTATOC PET radiomics for improved surgical planning in well-differentiated pancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2024; 51:2774-2783. [PMID: 38696129 DOI: 10.1007/s00259-024-06730-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 04/23/2024] [Indexed: 07/05/2024]
Abstract
PURPOSE Accurate identification of lymph node (LN) metastases is pivotal for surgical planning of pancreatic neuroendocrine tumours (PanNETs); however, current imaging techniques have sub-optimal diagnostic sensitivity. Aim of this study is to investigate whether [68Ga]Ga-DOTATOC PET radiomics might improve the identification of LN metastases in patients with non-functioning PanNET (NF-PanNET) referred to surgical intervention. METHODS Seventy-two patients who performed preoperative [68Ga]Ga-DOTATOC PET between December 2017 and March 2022 for NF-PanNET. [68Ga]Ga-DOTATOC PET qualitative assessment of LN metastases was measured using diagnostic balanced accuracy (bACC), sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). SUVmax, SUVmean, Somatostatin receptor density (SRD), total lesion SRD (TLSRD) and IBSI-compliant radiomic features (RFs) were obtained from the primary tumours. To predict LN involvement, these parameters were engineered, selected and used to train different machine learning models. Models were validated using tenfold repeated cross-validation and control models were developed. Models' bACC, SN, SP, PPV and NPV were collected and compared (Kruskal-Wallis, Mann-Whitney). RESULTS LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60%, SN = 24%, SP = 95%, PPV = 78% and NPV = 65%. The best-performing radiomic model provided a bACC = 70%, SN = 77%, SP = 61%, PPV = 60% and NPV = 83% (outperforming the control model, p < 0.05*). CONCLUSION In this study, [68Ga]Ga-DOTATOC PET radiomics allowed to increase diagnostic sensitivity in detecting LN metastases from 24 to 77% in NF-PanNET patients candidate to surgery. Especially in case of micrometastatic involvement, this approach might assist clinicians in a better patients' stratification.
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Affiliation(s)
- Paola Mapelli
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carolina Bezzi
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Samuele Ghezzo
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carla Canevari
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Patrizia Magnani
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Anna Battistella
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paola Scifo
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Valentina Andreasi
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Arturo Chiti
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Maria Picchio
- Vita-Salute San Raffaele University, Milan, Italy.
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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Centeno BA, Saieg M, Siddiqui MT, Perez-Machado M, Layfield LJ, Weynand B, Reid MD, Stelow EB, Lozano MD, Fukushima N, Cree IA, Mehrotra R, Schmitt FC, Field AS, Pitman MB. The World Health Organization Reporting System for Pancreaticobiliary Cytopathology: Overview and Summary. Cancer Cytopathol 2024; 132:396-418. [PMID: 38709670 DOI: 10.1002/cncy.22806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/12/2024] [Accepted: 01/17/2024] [Indexed: 05/08/2024]
Abstract
The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians.
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Affiliation(s)
| | - Mauro Saieg
- Santa Casa Medical School, Sao Paulo, Brazil
| | - Momin T Siddiqui
- Department of Pathology, Weill Cornell Medicine, New York, New York, USA
| | - Miguel Perez-Machado
- Department of Cellular Pathology, Royal Free Hampstead NHS Trust, London, England
| | - Lester J Layfield
- Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA
| | - Birgit Weynand
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium
| | - Michelle D Reid
- Department of Pathology, Emory University Hospital, Atlanta, Georgia, USA
| | - Edward B Stelow
- Department of Pathology, University of Virginia Hospital, Charlottesville, Virginia, USA
| | - Maria D Lozano
- Department of Pathology, Clinica University of Navarra, Pamplona, Spain
| | - Noriyoshi Fukushima
- Department of Diagnostic Pathology, Jichi Medical University Hospital, Shimotsuke, Japan
| | - Ian A Cree
- International Agency for Research on Cancer [IARC], World Health Organization, Lyon, France
| | - Ravi Mehrotra
- Indian Cancer Genomic Atlas, Centre for Health, Innovation and Policy Foundation, Noida, Uttar Pradesh, India
| | - Fernando C Schmitt
- Faculty of Medicine, Department of Pathology, University of Porto, Porto, Portugal
- CINTESIS@RISE, Porto University, Porto, Portugal
| | - Andrew S Field
- Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales, Australia
- University of New South Wales Sydney and University of Notre Dame, Sydney, New South Wales, Australia
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Firsova M, Treglia G, Sempoux C, Dromain C, Prior JO, Schaefer N, Boughdad S. Increased [ 68Ga]Ga-SST uptake in the uncinate pancreatic process in new digital PET/CT machine and potential association with clinical and histologic factors in NET patients. EJNMMI REPORTS 2024; 8:18. [PMID: 38910232 PMCID: PMC11194230 DOI: 10.1186/s41824-024-00203-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 04/10/2024] [Indexed: 06/25/2024]
Abstract
INTRODUCTION A physiological increase in the uptake of [68Ga]Ga-labeled somatostatin analogues ([68Ga]Ga-SST) PET tracers has been reported in the uncinate pancreatic process (UP) and might be even higher in latest generation of PET/CT scanners and might be falsely interpreted as NET. We aimed to investigate the uptake of UP in a large population of NET patients who underwent [68Ga]Ga-SST PET/CT with digital SiPM detectors. We also explored potential associations between UP uptake and various clinical, imaging, and pathological factors routinely assessed in NET patients. METHODS We analyzed all consecutive NET patients from July 2018 to June 2022 in this retrospective, single-center study. All patients underwent a [68Ga]Ga-SST PET/CT scan on a digital SiPM PET/CT scanner. On visual analysis, we distinguished between normal linear and homogenous UP uptake or abnormal if otherwise. We compared SUVmax/mean in patients with normal UP uptake to those with abnormal UP uptake with suspicious NET lesions on contrast-enhanced CT (ce-CT) and according to the site of the primary NET (pancreatic NET vs. other), patient gender (female vs. male) and tumor grade (grade 1-2 vs. 3) using a Mann-Whitney test. We also assessed the correlation between SUVmax/mean values in UP with patients' age, primary NET Ki-67 counting, and its SUVmax/mean, TLA and MTV values. RESULTS We included 131 NET patients with a total of 34 [68Ga]Ga-DOTATATE PET/CT and 113 [68Ga]Ga-DOTATOC PET/CT scans. An abnormal UP uptake was seen in 32 patients with 65.7% of suspicious NET lesion or extrinsic compression on morphological imaging. Normal UP uptake SUVmax/mean were measured in 115 [68Ga]Ga-SST scans (78.2%) with normal UP uptake and without suspicious lesion on morphological imaging. We found an average SUVmax of 12.3 ± 4.1 for [68Ga]Ga-DOTATATE and 19.8 ± 9.8 g/ml for [68Ga]Ga-DOTATOC, hence higher than those reported in the literature [SUVmax 5 ± 1.6 to 12.6 ± 2.2 g/ml] with significant difference with abnormal UP uptake and between both PET tracers (both p < 0.01). Significant results were a higher UP uptake on [68Ga]Ga-DOTATOC in male patients (p = 0.02) and significant associations between UP uptake on [68Ga]Ga-DOTATOC and SUVmax/mean of the primary tumor (ρ [0.337-0.363]; p [0.01-0.02]). CONCLUSION We confirmed a higher and very frequent UP uptake in latest SiPM-detector [68Ga]Ga-SST PET/CT with an even higher uptake in patients that had [68Ga]Ga-DOTATOC PET/CT. SUVmean/max were significantly higher in abnormal UP uptake but there were overlaps with UP SUV values for both [68Ga]Ga-SST and a correlation to morphological imaging is crucial. Besides, significant associations between UP uptake and SUVmean/max of the primary NET as well as patients' gender were seen in the larger cohort of [68Ga]Ga-DOTATOC patients suggesting that both physiological and pathological parameters could affect UP uptake.
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Affiliation(s)
- Maria Firsova
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Giorgio Treglia
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Via A. Gallino 12, 6500, Bellinzona, Switzerland
- Academic Education, Research and Innovation Area, General Directorate, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Christine Sempoux
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Pathology, Lausanne University Hospital, Lausanne, Switzerland
| | - Clarisse Dromain
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - John O Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Niklaus Schaefer
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Sarah Boughdad
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
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Papadopoulou-Marketou N, Tsoli M, Chatzellis E, Alexandraki KI, Kaltsas G. Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors. Cancers (Basel) 2024; 16:2075. [PMID: 38893191 PMCID: PMC11171219 DOI: 10.3390/cancers16112075] [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: 03/29/2024] [Revised: 05/19/2024] [Accepted: 05/20/2024] [Indexed: 06/21/2024] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine neoplasia type 1 (MEN1) syndrome. Other inherited syndromes associated with PanNETs include MEN4, von Hippel-Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). These syndromes are highly penetrant and their clinical manifestations may vary even among members of the same family. They are attributed to genetic mutations involving key molecular pathways regulating cell growth, differentiation, and angiogenesis. Pancreatic NETs in hereditary syndromes are often multiple, develop at a younger age compared to sporadic tumors, and are associated with endocrine and nonendocrine tumors derived from multiple organs. Lung NETs are not as common as PanNETs and are mostly encountered in MEN1 syndrome and include typical and atypical lung carcinoids. Early detection of PanNETs and LNETs related to inherited syndromes is crucial, and specific follow-up protocols need to be employed to optimize diagnosis and management. Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers. Optimal management and therapeutic decisions should be made in the context of a multidisciplinary team in specialized centers, whereas specific biomarkers aiming to identify patients denoted to follow a more aggressive course need to be developed.
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Affiliation(s)
- Nektaria Papadopoulou-Marketou
- Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.T.); (G.K.)
| | - Marina Tsoli
- Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.T.); (G.K.)
| | | | | | - Gregory Kaltsas
- Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.T.); (G.K.)
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Nießen A, Klaiber U, Lewosinska M, Nickel F, Billmann F, Hinz U, Büchler MW, Hackert T. Portal vein resection in pancreatic neuroendocrine neoplasms. Surgery 2024; 175:1154-1161. [PMID: 38262817 DOI: 10.1016/j.surg.2023.12.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 12/07/2023] [Accepted: 12/16/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND Surgery offers the only cure for borderline resectable or locally advanced pancreatic neuroendocrine neoplasms. Data on incidence, perioperative and long-term outcomes of portal vein resection for pancreatic neuroendocrine neoplasms are scarce. This study aimed to analyze the outcome and prognostic factors of portal vein resection in surgery for pancreatic neuroendocrine neoplasms. METHODS Consecutive patients were analyzed. Portal vein resection was classified according to the International Study Group of Pancreatic Surgery. Clinicopathologic features and overall and disease-free survival were assessed and compared with standard resection in a matched-pair analysis. RESULTS A total of 54 of 666 (8%) resected pancreatic neuroendocrine neoplasms patients underwent portal vein resection, including 7 (13%) tangential resections with venorrhaphy (type 1), 2 (4%) patch reconstructions (type 2), 35 (65%) end-to-end anastomoses (type 3), and 10 (19%) graft interpositions (type 4); 52% of those underwent pancreatoduodenectomy, 22% distal pancreatectomy, and 26% total pancreatectomy. Postoperative portal vein thrombosis occurred in 19%. Postoperative pancreatic fistula grades B and C (9% vs 16%; P = .357), complications Clavien-Dindo grade ≥IIIb (28% vs 13%; P = .071), and 90-day mortality rate (2% each) were not significantly different compared with 108 matched patients. The 5-year overall survival was 45% (standard resection: 68%; P = .432), and the 5-year disease-free survival was 25% (standard resection: 34%; P = .716). Radical resection was associated with 5-year overall survival of 51% and 5-year disease-specific survival of 75%. CONCLUSION This is the largest single-center analysis evaluating perioperative and long-term outcomes of portal vein resection for pancreatic neuroendocrine neoplasms. The postoperative complication rate after portal vein resection is comparable with standard resection. The 90-day mortality is low. Radical resection leads to excellent 5-year oncological survival.
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Affiliation(s)
- Anna Nießen
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. https://twitter.com/anna_niessen
| | - Ulla Klaiber
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Austria
| | - Magdalena Lewosinska
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Felix Nickel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franck Billmann
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany; Botton-Champalimaud Pancreatic Cancer Centre, Champalimaud Foundation, Lisbon, Portugal.
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Al-Darwish AS, Alsubaie WR, AlShammari W, AlaSheikh M, AlRashed M. Neuroendocrine tumor of the appendix masquerading as acute appendicitis with a mucocele on CT scan: a rare finding. Surg Case Rep 2024; 10:65. [PMID: 38499895 PMCID: PMC10948727 DOI: 10.1186/s40792-024-01870-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/14/2024] [Indexed: 03/20/2024] Open
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) of the appendix are rare and are often discovered incidentally during surgery for acute appendicitis or other unrelated conditions (Modlin et al. in Gastroenterology 128:1717-1751, 2005, Alsaad et al. in Oncol Rep 16:1105-1109, 2006, Frilling et al. in Lancet Oncol 15:e8-e21, 2014). These tumors can range from asymptomatic incidental findings to clinically significant tumors with metastases (Alsaad et al. in Oncol Rep 16:1105-1109, 2006, Gomes et al. in World J Emerg Surg 10:60, 2015, Paiva et al. in Eur J Cancer 38:702-705, 2002, Burke et al. in Am J Surg Pathol. 9:661-674, 1985). This case report presents a rare case of a NET of the appendix presenting as acute appendicitis. CASE DESCRIPTION A 23-year-old male presented with right lower quadrant abdominal pain, nausea, and vomiting for 2 days. A CT scan revealed a mucocoele of the appendix. The patient underwent laparoscopic appendectomy, and the appendix was sent for histopathological examination. The final pathological report confirmed a NET of the appendix with a Ki-67 index of 1% and no lymphovascular invasion. Due to tumor invasion to the cecum and its large size (3-4 cm), the patient underwent right hemicolectomy. The final histopathology report of the resected specimen confirmed the diagnosis of NET of the appendix. DISCUSSION The clinical diagnosis of NETs of the appendix can be challenging due to their rarity and non-specific presentation. Symptoms of NETs of the appendix can mimic those of acute appendicitis, making it difficult to differentiate between the two conditions. Imaging studies, such as CT scans, can provide valuable information about the size and location of the tumor (Gomes et al. in World J Emerg Surg 10:60, 2015, Maggard et al. in Ann Surg 240:117-122, 2004, Burke et al. in Am J Surg Pathol. 9:661-674, 1985, Frilling et al. in Lancet Oncol 15:e8-e21, 2014). However, the definitive diagnosis is made through histopathological examination of the resected specimen. The treatment of NETs of the appendix depends on factors such as the size, location, and grade of the tumor. Small tumors confined to the appendix with no lymph-vascular invasion can be treated with appendectomy alone, while larger tumors or those that have spread beyond the appendix may require more extensive surgery, such as right hemicolectomy (Gomes et al. in World J Emerg Surg 10:60, 2015, Mestier et al. in Dig Liver Dis 52:899-911, 2020, Maggard et al. in Ann Surg 240:117-122, 2004, Burke et al. in Am J Surg Pathol. 9:661-674, 1985, Frilling et al. in Lancet Oncol 15:e8-e21, 2014, Pavel et al. in Neuroendocrinology 103:172-185, 2016). In some cases, additional treatments such as chemotherapy or radiation therapy may be recommended. CONCLUSION This case report emphasizes the importance of considering NETs of the appendix in the differential diagnosis of acute appendicitis. Imaging studies can provide valuable information, but the definitive diagnosis is made through histopathological examination. The treatment approach for NETs of the appendix depends on various factors and requires a multidisciplinary approach for optimal management.
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Affiliation(s)
- Abdullah S Al-Darwish
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia.
- Department of Surgery, Arryan Hospital, Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia.
| | - Waad Rashaid Alsubaie
- Department of Pathology, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
| | - Waleed AlShammari
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
- Department of Surgery, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Muath AlaSheikh
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
| | - Muath AlRashed
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
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11
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Møller S, Langer SW, Slott C, Krogh J, Hansen CP, Kjaer A, Holmager P, Klose M, Garbyal RS, Knigge U, Andreassen M. Recurrence-Free Survival and Disease-Specific Survival in Patients with Pancreatic Neuroendocrine Neoplasms: A Single-Center Retrospective Study of 413 Patients. Cancers (Basel) 2023; 16:100. [PMID: 38201527 PMCID: PMC10777990 DOI: 10.3390/cancers16010100] [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: 10/27/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
INTRODUCTION The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial. AIM To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3). METHOD A single-center retrospective study including consecutive patients over a 20-year period. Multivariate Cox regression analyses were performed to identify risk factors. RESULTS 413 patients were included, with a mean (SD) age of 62 ± 14 years. In group 1 (n = 51), median (IQR) follow-up was 29 (21-34) months, and tumor size was 1.0 (0.8-1.4) cm. One progressed and had a tumor resection. In group 2 (n = 165), follow-up 59 (31-102) months, median tumor size 2 (1.2-3.4) cm, median Ki-67 index 5 (3-10)%, the 5-year recurrence rate was 21%. Tumor size (p < 0.001), Ki-67 index (p = 0.02), and location in the pancreatic head (p < 0.001) were independent risk factors. In group 3 (n = 197), follow-up 19 (6-46) months, median tumor size 4.2 (2.6-7.0) cm, Ki-67 index 17 (9-64)%, the median disease-specific survival was 22 (6-75) months-99 in NET G1; 54 in NET G2; 14 in NET G3; and 6 months in neuroendocrine carcinomas (NEC). Age (p = 0.029), plasma chromogranin A (p = 0.014), and proliferation, expressed by grade (p = 0.001) and Ki-67 index (p < 0.001), were risk factors. CONCLUSION Growth in pNET < 2 cm requiring surgery was observed in 1/51. Tumor size, Ki-67 index, and location in the head were prognostic factors for disease recurrence, while age, plasma chromogranin A, and proliferation predicted mortality in patients with unresectable disease or residual tumors after resection.
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Affiliation(s)
- Stine Møller
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Seppo W. Langer
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Oncology, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 1172 Copenhagen, Denmark
| | - Cecilie Slott
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Jesper Krogh
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 1172 Copenhagen, Denmark
| | - Carsten Palnæs Hansen
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Surgery and Transplantation, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Andreas Kjaer
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Biomedical Sciences, University of Copenhagen, 1172 Copenhagen, Denmark
| | - Pernille Holmager
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Marianne Klose
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Rajendra Singh Garbyal
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Pathology, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Surgery and Transplantation, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Mikkel Andreassen
- ENETS Center of Excellence, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (S.M.); (S.W.L.); (C.S.); (J.K.); (C.P.H.); (A.K.); (P.H.); (M.K.); (R.S.G.); (U.K.)
- Department of Endocrinology and Metabolism 7562, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 1172 Copenhagen, Denmark
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12
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Wójcik-Giertuga M, Malczewska-Herman A, Kos-Kudła B. The Risk of Venous Thromboembolism in Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:5477. [PMID: 38001737 PMCID: PMC10670321 DOI: 10.3390/cancers15225477] [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: 09/30/2023] [Revised: 11/15/2023] [Accepted: 11/18/2023] [Indexed: 11/26/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) differ from other malignancies in their ability to produce hormones and biogenic amines, as well as offer a better prognosis in well-differentiated tumors. There are no definite data on the occurrence of thromboembolic events in NENs and no recommendations regarding the use of antithrombotic prophylaxis in this group. Accurate assessment of the thromboembolic risk in NENs represents an important issue, in order to reduce morbidity and mortality due to complications of VTE. The aim of this work was to review the occurrence of thromboembolic events in NENs and the use of antithrombotic prophylaxis in this group. A total of 28 studies identified on PubMed were analyzed. NENs, especially of pancreatic primary, exhibit an increased thrombotic risk. Atypical VTE locations are quite common in NENs. Hormonally active NENs are associated with a significantly increased thromboembolic risk. Further studies in NENs are needed to evaluate the parameters of coagulation and fibrinolysis as predictive biomarkers for VTE complications.
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Affiliation(s)
- Monika Wójcik-Giertuga
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Ceglana 35, 40-514 Katowice, Poland; (A.M.-H.); (B.K.-K.)
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13
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Shintakuya R, Uemura K, Sumiyoshi T, Okada K, Baba K, Harada T, Murakami Y, Serikawa M, Ishii Y, Arihiro K, Takahashi S. Optimal Lymphadenectomy in Patients with Well-Differentiated Nonfunctioning Pancreatic Neuroendocrine Neoplasms. J Clin Med 2023; 12:6778. [PMID: 37959242 PMCID: PMC10647402 DOI: 10.3390/jcm12216778] [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: 09/30/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. Among patients with pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, metastases only at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. In conclusion, lymph node metastasis near the primary tumor was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms.
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Affiliation(s)
- Ryuta Shintakuya
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Kenta Baba
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Takumi Harada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Yoshiaki Murakami
- Department of Advanced Medicine, Hiroshima University, Hiroshima 739-8526, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University, Hiroshima 739-8526, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-8526, Japan
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14
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Pellat A, Barat M, Cottereau AS, Terris B, Coriat R. [Well-differentiated neuroendocrine tumors of the digestive tract: Focus on pancreatic neuroendocrine tumors]. Bull Cancer 2023; 110:955-967. [PMID: 36935319 DOI: 10.1016/j.bulcan.2023.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/16/2023] [Accepted: 03/01/2023] [Indexed: 03/19/2023]
Abstract
Pancreatic neuroendocrine tumors are rare tumors showing a rising incidence. They are well-differentiated tumors, classified by grade according to their Ki67 index value (grade 1 to 3). Pancreatic neuroendocrine tumors are mainly sporadic tumors but about 10% arise within endocrine tumor syndromes such as multiple endocrine neoplasia type 1. They can be responsible for functional syndromes or non-specific clinical symptoms depending on tumor extension. However, there is also an increase of incidental diagnoses of nonfunctional pancreatic neuroendocrine tumors with the widespread use of high-quality imaging techniques. About 50 % of pancreatic neuroendocrine tumors are diagnosed at a metastatic stage, with metastases often located in the liver. Chromogranin A, CT-scan and often an abdominal MRI, and functional imaging should be performed for tumor staging and follow-up. Imaging with PET/CT with 68Ga-labeled somatostatin analogues has the highest sensitivity for the diagnosis of pancreatic neuroendocrine tumors, while 18fluorodeoxyglucose PET/CT can sometimes be useful. Overall, they are rather indolent tumors with prolonged survival. Surgery is the recommended treatment in the localized setting, with the exception of small<2cm nonfunctional tumors that can be monitored with imaging techniques. For advanced tumors, there are several available treatments such as somatostatine analogues, chemotherapy, targeted therapies (sunitinib, everolimus), locoregional ablative therapies and Peptide Receptor Radiolabelled Therapy. The treatment strategy will depend on the initial tumor staging, tumor grade, aggressiveness and patient's choice.
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Affiliation(s)
- Anna Pellat
- AP-HP, hôpital Cochin, service de gastroentérologie et d'oncologie digestive, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France.
| | - Maxime Barat
- AP-HP, hôpital Cochin, service de radiologie, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France
| | - Anne-Ségolène Cottereau
- AP-HP, hôpital Cochin, service de médecine nucléaire, 27, rue du faubourg Saint-Jacques, 75014 Paris, France
| | - Benoit Terris
- AP-HP, hôpital Cochin, service d'anatomopathologie, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France
| | - Romain Coriat
- AP-HP, hôpital Cochin, service de gastroentérologie et d'oncologie digestive, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France
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15
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Wu W, Cai S, Chen R, Fu D, Ge C, Hao C, Hao J, Huang H, Jian Z, Jin G, Li F, Li H, Li S, Li W, Li Y, Liang T, Liu X, Lou W, Miao Y, Mou Y, Peng C, Qin R, Shao C, Sun B, Tan G, Wang H, Wang L, Wang W, Wang W, Wei J, Wu H, Wu Z, Yan C, Yang Y, Yin X, Yu X, Yuan C, Zhao Y. Consensus of clinical diagnosis and treatment for non-functional pancreatic neuroendocrine neoplasms with diameter <2 cm. JOURNAL OF PANCREATOLOGY 2023; 6:87-95. [DOI: 10.1097/jp9.0000000000000139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2025] Open
Abstract
In clinical practice, pancreatic neuroendocrine neoplasms (pNENs) with a diameter smaller than 2 cm are commonly referred to as small pNENs. Due to their generally favorable biological characteristics, the diagnosis and treatment of small pNENs differ from other pNENs and are somewhat controversial. In response to this, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association have developed a consensus on the diagnosis and treatment of small pNENs, which is based on evidence-based medicine and expert opinions. This consensus covers various topics, including concepts, disease assessment, treatment selection, follow-up, and other relevant aspects.
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Affiliation(s)
- Wenming Wu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Shouwang Cai
- Department of Hepatobiliary Surgery, PLA General Hospital, Beijing 100853, China
| | - Rufu Chen
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Deliang Fu
- Department of Pancreatic Surgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Chunlin Ge
- Department of Hepatobiliary and Pancreatic Surgery, Hunnan Division of The First Hospital of China Medical University, Shenyang 110167, China
| | - Chunyi Hao
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jihui Hao
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Heguang Huang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510000, China
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital Affiliated to Navy Medical University (Second Military Medical University), Shanghai 200433, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Haimin Li
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
| | - Shengping Li
- Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Weiqin Li
- Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
| | - Yixiong Li
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xubao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yi Miao
- Pancreas Centre, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yiping Mou
- Department of Gastrointestinal-Pancreatic Surgery, General Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
| | - Chenghong Peng
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chenghao Shao
- Department of Pancreatic-biliary Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
| | - Guang Tan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing 401147, China
| | - Lei Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Ji’nan 250012, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Junmin Wei
- Department of General Surgery, Beijing Hospital, Beijing 100730, China
| | - Heshui Wu
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Changqing Yan
- Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Yinmo Yang
- Department of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, China
| | - Xiaoyu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Pancreatic Cancer Institute Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Yupei Zhao
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
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16
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Mapelli P, Bezzi C, Muffatti F, Ghezzo S, Baldassi F, Schiavo Lena M, Andreasi V, Canevari C, Magnani P, De Cobelli F, Gianolli L, Partelli S, Falconi M, Picchio M. Somatostatin receptor activity assessed by 68Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging 2023; 50:2818-2829. [PMID: 37010579 DOI: 10.1007/s00259-023-06210-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 03/18/2023] [Indexed: 04/04/2023]
Abstract
PURPOSE To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery. METHODS This retrospective study included 72 consecutive patients with PanNET (January 2018-March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE. RESULTS Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040). CONCLUSION SRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients' management by preoperatively identifying subjects with more aggressive diseases.
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Affiliation(s)
- Paola Mapelli
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carolina Bezzi
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Samuele Ghezzo
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | | | - Valentina Andreasi
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carla Canevari
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Patrizia Magnani
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco De Cobelli
- Vita-Salute San Raffaele University, Milan, Italy
- Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luigi Gianolli
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Maria Picchio
- Vita-Salute San Raffaele University, Milan, Italy.
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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17
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Song H, Tan Q, Yuan Y, Liu X, Chen Y, Wang X. Preoperative acute pancreatitis and hyperenzymemia are associated with poor prognosis in patients with nonfunctional pancreatic neuroendocrine tumors. J Surg Oncol 2023; 127:1135-1142. [PMID: 36912877 DOI: 10.1002/jso.27227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/28/2023] [Accepted: 02/20/2023] [Indexed: 03/14/2023]
Abstract
BACKGROUND We aimed to investigate the prevalence of acute pancreatitis (AP) and hyperenzymemia as well as their clinical impact on postoperative survival outcomes in patients with pancreatic neuroendocrine tumors (PNETs). METHODS A retrospective cohort study of 218 patients who underwent radical surgical resection for nonfunctional PNETs (NF-PNETs) was conducted. Multivariate survival analysis was performed by the Cox proportional hazard model, with results expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS Of the 151 patients who met the inclusion criteria, the incidences of preoperative AP and hyperenzymemia were 7.9% (12/152) and 23.2% (35/151), respectively. The mean recurrence-free survival (RFS, 95% CI) for patients in control, AP, and hyperenzymemia groups was 136 (127-144), 88 (74-103), and 90 (61-122) months, with a 5-year RFS rate of 86.5%, 58.3%, and 68.9%, respectively. In the multivariable-adjusted Cox hazard model that included tumor grade and lymph node status, the adjusted HR of AP and hyperenzymemia for recurrence was 2.58 (95% CI: 1.47-7.86, p = 0.008) and 2.43 (95% CI: 1.08-7.06, p = 0.040). CONCLUSION Preoperative AP and hyperenzymemia are associated with poor RFS following radical surgical resection in NF-PNETs patients.
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Affiliation(s)
- Haiyu Song
- Department of Hepatobiliary and Pancreatic Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan Province, China
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qingquan Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yuan Yuan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xubao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yonghua Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xing Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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18
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Prete AM, Gonda TA. Endoscopic Ultrasound-Guided Local Ablative Therapies for the Treatment of Pancreatic Neuroendocrine Tumors and Cystic Lesions: A Review of the Current Literature. J Clin Med 2023; 12:jcm12093325. [PMID: 37176764 PMCID: PMC10179349 DOI: 10.3390/jcm12093325] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/02/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023] Open
Abstract
Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.
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Affiliation(s)
- Alexander M Prete
- Department of Medicine, New York University (NYU) Grossman School of Medicine, New York, NY 10016, USA
| | - Tamas A Gonda
- Division of Gastroenterology and Hepatology, New York University (NYU) Langone Health, New York, NY 10016, USA
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19
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Wang Y, Wang F, Qin Y, Lou X, Ye Z, Zhang W, Gao H, Chen J, Xu X, Yu X, Ji S. Recent progress of experimental model in pancreatic neuroendocrine tumors: drawbacks and challenges. Endocrine 2023; 80:266-282. [PMID: 36648608 DOI: 10.1007/s12020-023-03299-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 12/31/2022] [Indexed: 01/18/2023]
Abstract
The neuroendocrine neoplasm, in general, refers to a heterogeneous group of all tumors originating from peptidergic neurons and neuroendocrine cells. Neuroendocrine neoplasms are divided into two histopathological subtypes: well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Pancreatic neuroendocrine tumors account for more than 80% of pancreatic neuroendocrine neoplasms. Due to the greater proportion of pancreatic neuroendocrine tumors compared to pancreatic neuroendocrine carcinoma, this review will only focus on them. The worldwide incidence of pancreatic neuroendocrine tumors is rising year by year due to sensitive detection with an emphasis on medical examinations and the improvement of testing technology. Although the biological behavior of pancreatic neuroendocrine tumors tends to be inert, distant metastasis is common, often occurring very early. Because of the paucity of basic research on pancreatic neuroendocrine tumors, the mechanism of tumor development, metastasis, and recurrence are still unclear. In this context, the representative preclinical models simulating the tumor development process are becoming ever more widely appreciated to address the clinical problems of pancreatic neuroendocrine tumors. So far, there is no comprehensive report on the experimental model of pancreatic neuroendocrine tumors. This article systematically summarizes the characteristics of preclinical models, such as patient-derived cell lines, patient-derived xenografts, genetically engineered mouse models, and patient-derived organoids, and their advantages and disadvantages, to provide a reference for further studies of neuroendocrine tumors. We also highlight the method of establishment of liver metastasis mouse models.
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Affiliation(s)
- Yan Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Fei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xin Lou
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Zeng Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wuhu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Heli Gao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jie Chen
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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20
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Rossi G, Petrone MC, Healey AJ, Arcidiacono PG. Approaching Small Neuroendocrine Tumors with Radiofrequency Ablation. Diagnostics (Basel) 2023; 13:1561. [PMID: 37174952 PMCID: PMC10177414 DOI: 10.3390/diagnostics13091561] [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: 03/21/2023] [Revised: 04/20/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
In recent years, small pancreatic neuroendocrine tumors (pNETs) have shown a dramatic increase in terms of incidence and prevalence, and endoscopic ultrasound (EUS) radiofrequency ablation (RFA) is one potential method to treat the disease in selected patients. As well as the heterogeneity of pNET histology, the studies reported in the literature on EUS-RFA procedures for pNETs are heterogeneous in terms of ablation settings (particularly ablation powers), radiological controls, and radiological indications. The aim of this review is to report the current reported experience in EUS-RFA of small pNETs to help formulate the procedure indications and ablation settings. Another aim is to evaluate the timing and the modality of the radiological surveillance after the ablation. Moreover, new studies on large-scale series are needed in terms of the safety and long-term oncological efficacy of RFA on these small lesions.
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Affiliation(s)
- Gemma Rossi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Maria Chiara Petrone
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Andrew J. Healey
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, 20132 Milan, Italy
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21
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Konstantinoff KS, Morani AC, Hope TA, Bhosale PR, Francis IR, Yano M, Iravani A, Trikalinos NA, Itani M. Pancreatic neuroendocrine tumors: tailoring imaging to specific clinical scenarios. Abdom Radiol (NY) 2023; 48:1843-1853. [PMID: 36737523 DOI: 10.1007/s00261-022-03737-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 02/05/2023]
Abstract
The clinical and imaging presentation of pancreatic neuroendocrine tumors (PanNETs) is variable and depends on tumor grade, stage, and functional status. This degree of variability combined with a multitude of treatment options and imaging modalities results in complexity when choosing the most appropriate imaging studies across various clinical scenarios. While various guidelines exist in the management and evaluation of PanNETs, there is an overall lack of consensus and detail regarding optimal imaging guidelines and protocols. This manuscript aims to fill gaps where current guidelines may lack specificity regarding the choice of the most appropriate imaging study in the diagnosis, treatment planning, monitoring, and surveillance of PanNETs under various clinical scenarios.
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Affiliation(s)
- Katerina S Konstantinoff
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, The University of California, San Francisco, 185 Berry Street Lobby 6, San Francisco, CA, 94107, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Isaac R Francis
- Department of Radiology, Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Amir Iravani
- Department of Radiology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Nikolaos A Trikalinos
- Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA.
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22
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Marcal LP, Chuang HH, Tran Cao HS, Halperin DM. Pancreatic Neuroendocrine Tumors. ONCOLOGIC IMAGING : A MULTIDISCIPLINARY APPROACH 2023:197-217. [DOI: 10.1016/b978-0-323-69538-1.00014-8] [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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23
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Veenstra EB, Noordzij W, Erba PA. Neuroendocrine Neoplasm Imaging and Image-Guided Therapies. MULTIMODALITY IMAGING AND INTERVENTION IN ONCOLOGY 2023:419-439. [DOI: 10.1007/978-3-031-28524-0_19] [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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Chen L, Wang W, Jin K, Yuan B, Tan H, Sun J, Guo Y, Luo Y, Feng ST, Yu X, Chen MH, Chen J. Special issue "The advance of solid tumor research in China": Prediction of Sunitinib efficacy using computed tomography in patients with pancreatic neuroendocrine tumors. Int J Cancer 2023; 152:90-99. [PMID: 36111424 DOI: 10.1002/ijc.34294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 11/11/2022]
Abstract
Clinically effective methods to predict the efficacy of sunitinib, for patients with metastatic or locally advanced pancreatic neuroendocrine tumors (panNET) are scarce, making precision treatment difficult. This study aimed to develop and validate a computed tomography (CT)-based method to predict the efficacy of sunitinib in patients with panNET. Pretreatment CT images of 171 lesions from 38 patients with panNET were included. CT value ratio (CT value of tumor/CT value of abdominal aorta from the same patient) and radiomics features were extracted for model development. Receiver operating curve (ROC) with area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the proposed model. Tumor shrinkage of >10% at first follow-up after sunitinib treatment was significantly associated with longer progression-free survival (PFS; P < .001) and was used as the major treatment outcome. The CT value ratio could predict tumor shrinkage with AUC of 0.759 (95% confidence interval [CI], 0.685-0.833). We then developed a radiomics signature, which showed significantly higher AUC in training (0.915; 95% CI, 0.866-0.964) and validation (0.770; 95% CI, 0.584-0.956) sets than CT value ratio. DCA also confirmed the clinical utility of the model. Subgroup analysis showed that this radiomics signature had a high accuracy in predicting tumor shrinkage both for primary and metastatic tumors, and for treatment-naive and pretreated tumors. Survival analysis showed that radiomics signature correlated with PFS (P = .020). The proposed radiomics-based model accurately predicted tumor shrinkage and PFS in patients with panNET receiving sunitinib and may help select patients suitable for sunitinib treatment.
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Affiliation(s)
- Luohai Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei Wang
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Bing Yuan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Huangying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Jian Sun
- Department of Biliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Guo
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanji Luo
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Min-Hu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
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Abstract
Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.
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Ghezzo S, Bezzi C, Neri I, Mapelli P, Presotto L, Gajate AMS, Bettinardi V, Garibotto V, De Cobelli F, Scifo P, Picchio M. Radiomics and artificial intelligence. CLINICAL PET/MRI 2023:365-401. [DOI: 10.1016/b978-0-323-88537-9.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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27
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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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Bloemen H, Kneepkens K, Deraedt K, Ivanova A, Sergeant G, Mebis J, Van der Speeten K. Evaluation of quality of clinical management of neuroendocrine tumors. CANCER INNOVATION 2022; 1:305-315. [PMID: 38089084 PMCID: PMC10686178 DOI: 10.1002/cai2.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/10/2022] [Accepted: 11/18/2022] [Indexed: 10/15/2024]
Abstract
Background Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms predominantly found in the gastrointestinal and bronchopulmonary tractus. Despite a rising incidence, implementation of evidence-based standardized care for this heterogenous group remains challenging. The European Neuroendocrine Tumor Society regularly reviews guidelines regarding diagnostic and treatment strategies for NETs. The aim of this study is to shed light on the care of patients with a NET in Belgian Limburg, to provide data as a basis for future studies and to check whether data and results are according to consensus guidelines and outcomes described in literature. Methods Our study concerned a detailed observational data collection of two large Belgian hospitals (Jessa Hospital Hasselt and Hospital Oost-Limburg Genk) with special interest in patient profile, quality of pathology reports, use of diagnostic imaging, and overall survival. Data on 188 patients were assembled between January 2010 and December 2014 with follow-up until June 2016 (median follow-up: 33.6 months). Results Fifty percent of patients were male. NETs were located mainly in the digestive tract (63.8%) and lung (20.2%). Appendiceal NETs were diagnosed at a significantly younger age than other tumors (41.3 vs. 64.0 years). Overall, a mean pathology report quality score of 3.0/5 was observed with the highest scores for small bowel NETs. Diagnostic and nuclear imaging was performed in 74.5% and 29.8% of cases, respectively. Seventy-four percent of the population survived until the end of the observation period with highest survival rates for appendiceal and small bowel NETs. Conclusion Overall, epidemiological results were comparable with findings in the literature. Gastrointestinal NETs met most of the requirements of qualitative pathology reporting and diagnostic imaging as listed in the European Neuroendocrine Tumor Society consensus guidelines. However, consensus with regard to bronchopulmonary NETs is still scarce and remains an objective for future research. Moreover, discussing treatment strategies in specialized multidisciplinary tumor boards would facilitate regional care.
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Affiliation(s)
- Hannah Bloemen
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
| | - Kristien Kneepkens
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
| | - Karen Deraedt
- Department of Pathology and Department Future HealthZiekenhuis Oost‐LimburgGenkBelgium
| | - Anna Ivanova
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
| | - Gregory Sergeant
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
- Department of Abdominal Surgery and Department Jessa & ScienceJessa HospitalHasseltBelgium
| | - Jeroen Mebis
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
- Department of Medical Oncology and Department Jessa & ScienceJessa HospitalHasseltBelgium
| | - Kurt Van der Speeten
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
- Department of Surgical Oncology and Department Future HealthZiekenhuis Oost‐LimburgGenkBelgium
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Nießen A, Schimmack S, Lewosinska M, Hinz U, Bechtiger FA, Hackert T, Büchler MW, Strobel O. Lymph node metastases and recurrence in pancreatic neuroendocrine neoplasms. Surgery 2022; 172:1791-1799. [PMID: 36180252 DOI: 10.1016/j.surg.2022.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 08/09/2022] [Accepted: 08/19/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND The impact of lymph node metastasis on survival in pancreatic neuroendocrine neoplasms as well as their best surgical treatment is controversial. We aimed to determine the frequency and prognostic impact of lymph node involvement in pancreatic neuroendocrine neoplasms. METHODS Patients undergoing pancreatic resections for pancreatic neuroendocrine neoplasms between 2001 and 2019 were retrospectively analyzed based on a prospective database. Clinicopathological parameters and perioperative outcome were assessed. Overall and disease-free survival was analyzed. Subgroup analysis was performed for sporadic, nonfunctional pancreatic neuroendocrine neoplasms without distant metastases and ≥4 analyzed lymph nodes. RESULTS Of 605 surgically resected pancreatic neuroendocrine neoplasms, 55% were G1, 36% were G2, and 9% were G3 differentiated. At the time of resection, 34% of patients had lymph node metastasis, and 16% had distant metastases. For subgroup analysis, 314 patients were analyzed. Lymph node metastases occurred in 36% of patients and were most frequent in G3 patients (67%). An increase in tumor size and advancement was associated with higher rates of lymph node metastasis, and disease-free survival was significantly impaired. Significant differences in disease-free survival were observed between 1 and 3 (5-year disease-free survival 52%) and ≥4 positive lymph nodes (5-year disease-free survival 28%), as well as when G3 tumors were excluded. In multivariable analysis, grading, tumor stage, and especially lymph node metastases as well as the proposed pN1 and pN2 categories were confirmed as independent predictors of recurrence. CONCLUSION The presence and extent of lymph node involvement has considerable prognostic impact in pancreatic neuroendocrine neoplasms. This study, for the first time, validated the proposed pN2 stage for well-differentiated pancreatic neuroendocrine neoplasms.
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Affiliation(s)
- Anna Nießen
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany. https://twitter.com/anna_niessen
| | - Simon Schimmack
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Magdalena Lewosinska
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Ulf Hinz
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Fabiola A Bechtiger
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Markus W Büchler
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Oliver Strobel
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany; Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Austria.
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Galgano SJ, Morani AC, Gopireddy DR, Sharbidre K, Bates DDB, Goenka AH, Arif-Tiwari H, Itani M, Iravani A, Javadi S, Faria S, Lall C, Bergsland E, Verma S, Francis IR, Halperin DM, Chatterjee D, Bhosale P, Yano M. Pancreatic neuroendocrine neoplasms: a 2022 update for radiologists. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3962-3970. [PMID: 35244755 DOI: 10.1007/s00261-022-03466-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/17/2022] [Accepted: 02/18/2022] [Indexed: 01/18/2023]
Abstract
Pancreatic neuroendocrine neoplasms (PaNENs) are a unique group of pancreatic neoplasms with a wide range of clinical presentations and behaviors. Given their heterogeneous appearance and increasing detection on cross-sectional imaging, it is essential that radiologists understand the variable presentation and distinctions PaNENs display compared to other pancreatic neoplasms. Additionally, some of these neoplasms may be hormonally functional, and it is imperative that radiologists be aware of the common clinical presentations of hormonally active PaNENs. Knowledge of PaNEN pathology and treatments may influence which imaging modality is optimal for each patient. Each imaging modality used for PaNENs has distinct advantages and disadvantages, particularly in different treatment settings. Thus, the focus of this manuscript is to provide an update for the radiologist on PaNEN pathology, imaging, and treatments.
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Affiliation(s)
- Samuel J Galgano
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA.
| | | | - Dheeraj R Gopireddy
- Department of Radiology, University of Florida-Jacksonville, Jacksonville, FL, USA
| | - Kedar Sharbidre
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - David D B Bates
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Hina Arif-Tiwari
- Department of Radiology, University of Arizona-Tuscon, Tuscon, AZ, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Amir Iravani
- Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Sanaz Javadi
- Department of Radiology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Silvana Faria
- Department of Radiology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Chandana Lall
- Department of Radiology, University of Florida-Jacksonville, Jacksonville, FL, USA
| | - Emily Bergsland
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Sadhna Verma
- Department of Radiology, University of Cincinnati, Cincinnati, OH, USA
| | - Isaac R Francis
- Department of Radiology, Michigan Medicine, Ann Arbor, MI, USA
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Deyali Chatterjee
- Department of Pathology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Priya Bhosale
- Department of Radiology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Arizona, Scottsdale, AZ, USA
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Qualitative imaging features of pancreatic neuroendocrine neoplasms predict histopathologic characteristics including tumor grade and patient outcome. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3971-3985. [PMID: 35166939 DOI: 10.1007/s00261-022-03430-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/22/2022] [Accepted: 01/25/2022] [Indexed: 01/18/2023]
Abstract
OBJECTIVES To identify PanNEN imaging features associated with tumor grade and aggressive histopathological features. METHODS Associations between histopathological and imaging features of resected PanNEN were retrospectively tested. Histopathologic features included WHO grade, lymphovascular invasion (LVI), growth pattern (infiltrative, circumscribed), and intratumoral fibrosis (mature, immature). Imaging features included size, degree/uniformity of enhancement, progressive enhancement, contour, infiltrative appearance (infiltrativeim), calcifications, cystic components, tumor thrombus, vascular occlusion (VO), duct dilatation, and atrophy. Multinomial logistic regression analyses evaluated the magnitude of associations. Association of variables with outcome was assessed using Cox-proportional hazards regression. RESULTS 133 patients were included. 3 imaging features (infiltrativeim, ill-defined contour [contourill], and VO) were associated with all histopathologic parameters and poor outcome. Increase in grade increased odds of contourill by 15.6 times (p = 0.0001, 95% CI 3.8-64.4). PanNEN with VO were 51.1 times (p = 0.0002, 6.5-398.6) more likely to demonstrate LVI. For PanNEN with contourill, infiltrative growth pattern was 51.3 times (p < 0.0001, 9.1-288.4), and fibrosis was 14 times (p = 0.0065, 2.1-93.7) more likely. Contourill was associated with decreased recurrence-free survival (p = 0.0003, HR 18.29, 3.83-87.3) and VO (p = 0.0004, HR6.08, 2.22-16.68) with decreased overall survival. CONCLUSIONS Infiltrativeim, contourill, and VO on imaging are associated with higher grade/histopathological parameters linked to tumor aggression, and poor outcome.
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Javed AA, Pulvirenti A, Zheng J, Michelakos T, Sekigami Y, Razi S, McIntyre CA, Thompson E, Klimstra DS, Deshpande V, Singhi AD, Weiss MJ, Wolfgang CL, Cameron JL, Wei AC, Zureikat AH, Ferrone CR, He J. A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study. Surgery 2022; 172:1800-1806. [PMID: 36192215 DOI: 10.1016/j.surg.2022.08.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/25/2022] [Accepted: 08/19/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. METHODS A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. RESULTS Nodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71-7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03-1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63-0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. CONCLUSION Our model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.
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Affiliation(s)
- Ammar A Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. http://www.twitter.com/ammar_asrar
| | | | - Jian Zheng
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Samrah Razi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Caitlin A McIntyre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Elizabeth Thompson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - David S Klimstra
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Vikram Deshpande
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Aatur D Singhi
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | | | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
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Contrast-Enhanced Harmonic Endoscopic Ultrasound for Diagnosis of the Aggressiveness of Pancreatic Neuroendocrine Neoplasm. Diagnostics (Basel) 2022; 12:diagnostics12122988. [PMID: 36552995 PMCID: PMC9777008 DOI: 10.3390/diagnostics12122988] [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: 11/11/2022] [Revised: 11/24/2022] [Accepted: 11/25/2022] [Indexed: 12/03/2022] Open
Abstract
The purpose of this study is to clarify the associations between the enhancement patterns on contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and the aggressiveness and prognosis of pancreatic neuroendocrine neoplasms (PanNENs). Patients who underwent CH-EUS and were pathologically diagnosed with PanNEN were included in this study. Patients were divided into three groups according to contrast-enhancement patterns on early-phase and late-phase imaging: “Group A”, vascular rich in both phases; “Group B”, vascular rich and vascular poor in early and late phases, respectively; “Group C”, vascular poor in both phases. Of 39 patients, 25 were assigned to Group A, 7 to Group B, and 7 to Group C. The median overall survival was not reached in Groups A and B and was 335 days in Group C (p < 0.001). The 1-year survival rates were 100% in Group A, 60% in Group B, and 43% in Group C. Patients in Group C showed the shortest overall survival among the three groups. The vascular-poor pattern on late-phase CH-EUS had the highest sensitivity, specificity, and accuracy for aggressive PanNENs among the patterns analyzed on CH-EUS and CECT (84.6%, 91.7%, and 89.2%, respectively). CH-EUS is useful for the diagnosis of and predicting the prognosis of PanNENs.
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Saleh M, Bhosale PR, Yano M, Itani M, Elsayes AK, Halperin D, Bergsland EK, Morani AC. New frontiers in imaging including radiomics updates for pancreatic neuroendocrine neoplasms. Abdom Radiol (NY) 2022; 47:3078-3100. [PMID: 33095312 DOI: 10.1007/s00261-020-02833-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/07/2020] [Accepted: 10/12/2020] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To illustrate the applications of various imaging tools including conventional MDCT, MRI including DWI, CT & MRI radiomics, FDG & DOTATATE PET-CT for diagnosis, staging, grading, prognostication, treatment planning and assessing treatment response in cases of pancreatic neuroendocrine neoplasms (PNENs). BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are very diverse clinically & biologically. Their treatment and prognosis depend on staging and primary site, as well as histological grading, the importance of which is also reflected in the recently updated WHO classification of GEP NENs. Grade 3 poorly differentiated neuroendocrine carcinomas (NECs) are aggressive & nearly always advanced at diagnosis with poor prognosis; whereas Grades-1 and 2 well-differentiated neuroendocrine tumors (NETs) can be quite indolent. Grade 3 well-differentiated NETs represent a new category of neoplasm with an intermediate prognosis. Importantly, the evidence suggest grade heterogeneity can occur within a given tumor and even grade progression can occur over time. Emerging evidence suggests that several non-invasive qualitative and quantitative imaging features on CT, dual-energy CT (DECT), MRI, PET and somatostatin receptor imaging with new tracers, as well as texture analysis, may be useful to grade, prognosticate, and accurately stage primary NENs. Imaging features may also help to inform choice of treatment and follow these neoplasms post-treatment. CONCLUSION GEP NENs treatment and prognosis depend on the stage as well as histological grade of the tumor. Traditional ways of imaging evaluation for diagnosis and staging does not yet yield sufficient information to replace operative and histological evaluation. Recognition of important qualitative imaging features together with quantitative features and advanced imaging tools including functional imaging with DWI MRI, DOTATATE PET/CT, texture analysis with radiomics and radiogenomic features appear promising for more accurate staging, tumor risk stratification, guiding management and assessing treatment response.
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Affiliation(s)
- Mohammed Saleh
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, Phoenix, AZ, 77030, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Ahmed K Elsayes
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Daniel Halperin
- GI Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Emily K Bergsland
- University of California San Francisco, San Francisco, CA, 94143, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA.
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Fernandes CJ, Leung G, Eads JR, Katona BW. Gastroenteropancreatic Neuroendocrine Tumors. Gastroenterol Clin North Am 2022; 51:625-647. [PMID: 36153114 DOI: 10.1016/j.gtc.2022.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
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Affiliation(s)
- Conrad J Fernandes
- Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Galen Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Jennifer R Eads
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA.
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Molasy B, Zemła P, Mrowiec S, Grudzińska E, Kuśnierz K. Evaluation of Risk Factors for Distant and Lymph Node Metastasis of Pancreatic Neuroendocrine Tumors. Ther Clin Risk Manag 2022; 18:745-752. [PMID: 35937972 PMCID: PMC9346299 DOI: 10.2147/tcrm.s361332] [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: 02/09/2022] [Accepted: 05/30/2022] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Metastases of pancreatic neuroendocrine tumors (pNETs) can be found at the time of diagnosis in 20-50% of cases. Small asymptomatic tumors may be left for observation; however, they can metastasize. The aim of the study was to evaluate risk factors for distant and lymph node metastases of pNETs. PATIENTS AND METHODS One hundred and fourteen patients with postoperatively confirmed pNET were analyzed retrospectively in a single ENETS Center of Excellence. The relationship between location, size, differentiation of the tumor, and occurrence of lymph node and distant metastases was analyzed. RESULTS pNETs' location was pancreatic head - 38 (33.3%), body or tail - 68 (59.7%), and 8 (7.0%) involved the entire organ. Fifty-six (49.1%) tumors were graded G1, 50 (43.9%) G2, and 8 (7.0%) G3. Seventy-two (63.2%) tumors were ≥2 cm in diameter, and 42 (36.8%) <2 cm. Twenty-two (19.3%) patients had distant metastases and 47 (41.2%) had lymph node metastases. In ≥2 cm tumors distant and lymph node metastases were more frequent (p < 0.05). Distant metastases incidence was significantly higher in distally located tumors (p = 0.01) and in G2 and G3 tumors (p < 0.01). In 9.5% of <2cm tumors, distant metastases were present at diagnosis. CONCLUSION Distant metastases are more often found in larger, distally located pNETs grade G2 and G3, while a higher occurrence of lymph node metastases seems to be associated only with larger tumor size. A considerable number of tumors <2 cm in size have distant metastases already at the diagnosis, which might indicate the need for careful qualification of smaller lesions for observation.
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Affiliation(s)
- Bartosz Molasy
- Students’ Scientific Society of the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
- Department of General Surgery, St Alexander Hospital, Kielce, Poland
| | - Patryk Zemła
- Students’ Scientific Society of the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
| | - Sławomir Mrowiec
- Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
| | - Ewa Grudzińska
- Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
| | - Katarzyna Kuśnierz
- Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
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Pan Q, Yang W, Zhang Z, Shao Z. Rare Bone Metastasis of Neuroendocrine Tumors of Unknown Origin: A Case Report and Literature Review. Orthop Surg 2022; 14:2766-2775. [PMID: 35856167 PMCID: PMC9531072 DOI: 10.1111/os.13384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 05/26/2022] [Accepted: 06/05/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND The neuroendocrine tumor (NET) is rare, accounting for about 0.5% of all tumors. NETs have the characteristics of metastasis, especially lymph nodes, liver, spleen, and bone. CASE PRESENTATION We report a 30-year-old man diagnosed with a NET with bone metastasis and presented with waist and leg pain. The imaging findings of this case showed multiple osteosclerosis and no apparent bone destruction. We collected the patient's previous examinations, including laboratory, imaging, and pathological examination to get a precise diagnosis. Given this case, we carried out symptomatic support treatment to relieve the patients' pain symptoms. CONCLUSION Bone metastases from NETs of unknown primary site are rare in both clinical and imaging manifestations. The disease is mainly manifested as multiple osteosclerosis, accompanied by muscle soreness and pain. It is recommended to try chemotherapy for this disorder.
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Affiliation(s)
- Qing Pan
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenbo Yang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhicai Zhang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zengwu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Analysis of Prognostic Risk Factors of Endoscopic Submucosal Dissection (ESD) and Curative Resection of Gastrointestinal Neuroendocrine Neoplasms. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:5248256. [PMID: 35854772 PMCID: PMC9286938 DOI: 10.1155/2022/5248256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/08/2022] [Accepted: 06/02/2022] [Indexed: 11/22/2022]
Abstract
Objective To explore the prognostic risk factors of ESD curative resection of gastrointestinal-neuroendocrine neoplasms (GI-NENs). Methods A total of 97 patients treated with ESD successfully in our hospital were selected, their surgical site, size, number of resection lesions, operation time, intraoperative complications (such as bleeding and perforation), and treatment status were recorded, and the number of hemostatic clamps used after the postoperative follow-up results and the independent risk factors for ESD complications were obtained through the comparison between the noncomplication group and the ESD complication group using regression analysis. Results A total of 97 patients with gastrointestinal neuroendocrine tumors were treated with ESD. 61 were males, 36 were females, the ratio of male to female was 1.7 : 1, onset age was 20–78 years old, and median onset age was 50 years old. In 81 cases, tumors were located in the stomach, 10 in the duodenum, and 6 in the rectum. A total of 103 lesions were detected by endoscopy, including 1 case with 2 sites in the stomach, 5 cases with 2 sites in the rectum, and the rest were single. The tumor diameter was 0.3 ∼ 2.5 cm, and the median diameter was 0.6 cm; there were 25 sites with a diameter less than 5 cm. There were 57 places with 10 mm, 16 places with 10–15 mm, and 5 places with >15 mm. All ESD operations were performed in one piece, with a total resection rate of 100%; 89.6% (60/67) of postoperative pathology showed negative basal, and 90.3% (56/62) showed negative resection margin, with a complete resection rate of 88.9% (48/54). ESD's operation time is 6 ∼ 66 min, and the median time is 18 min. During the operation, 5 cases had small amount of bleeding, 3 cases were perforated, 2 cases of delayed postoperative bleeding, 1 case of bleeding was caused by the patient's failure to follow the advice of the doctor to eat a large amount of solid food too early, and 1 case of delayed perforation (all recovered and discharged). ESD operation that bled, age, gender, and perforation location, pathological grade, pathological classification, tumor diameter, tumor surface, operation time, number of titanium clips, origin, echo uniformity, and echo level were statistically insignificant (P > 0.05). Postoperative bleeding was related to the operation time (P=0.017), but it was not an independent risk factor for postoperative bleeding (P=0.118; OR, 0.226; 95% CI, 0.035–1.461). 59 cases were followed up by endoscopy after the operation, and recurrence or no new tumors were found. Conclusion ESD is an effective and safe treatment method for gastrointestinal neuroendocrine tumors with a diameter of 1-2 cm without invading the muscularis propria. The intraoperative complications seem to have little relationship with the patient; postoperative delayed bleeding is closely related to the ESD operation time but it is not an independent risk factor.
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Dietrich CF, Shi L, Koch J, Löwe A, Dong Y, Cui X, Worni M, Jenssen C. Early detection of pancreatic tumors by advanced EUS imaging. Minerva Gastroenterol (Torino) 2022; 68:133-143. [PMID: 33337117 DOI: 10.23736/s2724-5985.20.02789-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2023]
Abstract
The early detection of pancreatic ductal adenocarcinoma (PDAC) dramatically improves outcome. All available state-of-the-art imaging methods allow early detection with EUS being the best technique for exclusion of PDAC and detection of very early PDAC. Etiological differentiation of small SPL is important to guide individually tailored patients' management including radical surgery in resectable PDAC, medical (neoadjuvant or palliative intended) treatment in patients with non-resectable malignancy, pancreatic parenchyma saving strategies in some non-PDAC, and follow-up in particular in low-grade PanNEN or other small benign lesions. Multimodality EUS imaging including B-Mode assessment, elastography, contrast-enhancement and EUS-guided sampling is the most appropriate technique for diagnosis and risk assessment of small SPL. We present a review discussing modern (endoscopic) ultrasound imaging techniques including contrast enhanced ultrasound and elastography for the early detection and characterization of solid pancreatic lesions.
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Affiliation(s)
- Christoph F Dietrich
- Department Allgemeine Innere Medizin, Beau Site Clinic, Salem-Spital, Kliniken Hirslanden, Bern, Switzerland -
| | - Long Shi
- Department of Ultrasound, Jingmen N.2 People's Hospital, Jingmen, China
| | - Jonas Koch
- Department Allgemeine Innere Medizin, Beau Site Clinic, Salem-Spital, Kliniken Hirslanden, Bern, Switzerland
| | - Axel Löwe
- Department Allgemeine Innere Medizin, Beau Site Clinic, Salem-Spital, Kliniken Hirslanden, Bern, Switzerland
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinwu Cui
- Department of Medical Ultrasound, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Mathias Worni
- Department of Visceral Surgery, Clarunis, St. Clara Hospital and University Hospital, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
- Campus SLB, Swiss Institute for Translational and Entrepreneurial Medicine, Stiftung Lindenhof, Bern, Switzerland
- Department of Surgery, Beau Site Clinic, Bern, Switzerland
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Märkisch Oderland, Strausberg, Germany
- Brandenburg Institute for Clinical Ultrasound, Medical University Brandenburg, Neuruppin, Germany
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Lin ZQ, Li X, Yang Y, Wang Y, Zhang XY, Zhang XX, Guo J. Nonfunctional pancreatic neuroendocrine tumours misdiagnosed as autoimmune pancreatitis: A case report and review of literature. World J Clin Cases 2022; 10:4886-4894. [PMID: 35801029 PMCID: PMC9198893 DOI: 10.12998/wjcc.v10.i15.4886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/29/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonfunctional pancreatic neuroendocrine tumours are difficult to diagnose in the early stage of disease due to a lack of clinical symptoms, but they can rarely manifest as autoimmune pancreatitis. Autoimmune pancreatitis is an uncommon disease that may cause recurrent acute pancreatitis and is therefore often regarded as a special type of chronic pancreatitis.
CASE SUMMARY We report a case of a 42-year-old female who had nonspecific upper abdominal pain for 4 years and radiological abnormalities of the pancreas that mimicked autoimmune pancreatitis. The symptoms and pancreatic imaging did not improve following 1 year of steroid therapy. Finally, pancreatic biopsy was performed through endoscopic ultrasonography-guided fine-needle aspiration biopsy, and nonfunctional pancreatic neuroendocrine tumours were ultimately diagnosed. Pancreatectomy has resolved her symptoms.
CONCLUSION Therefore, the differentiation of nonfunctional pancreatic neuroendocrine tumours from autoimmune pancreatitis is very important, although it is rare. We propose that endoscopic ultrasonography-guided fine-needle aspiration biopsy should be performed if imaging characteristics are equivocal or the diagnosis is in question.
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Affiliation(s)
- Zi-Qi Lin
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xin Li
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Yang
- Laboratory Medicine, West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yi Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Ying Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Xin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia Guo
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Nießen A, Bechtiger FA, Hinz U, Lewosinska M, Billmann F, Hackert T, Büchler MW, Schimmack S. Enucleation Is a Feasible Procedure for Well-Differentiated pNEN-A Matched Pair Analysis. Cancers (Basel) 2022; 14:cancers14102570. [PMID: 35626174 PMCID: PMC9139922 DOI: 10.3390/cancers14102570] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 02/05/2023] Open
Abstract
The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001−2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95−170) versus 263 (172−337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7−11) versus 10 (8−17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.
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Calderwood AH, Sawhney MS, Thosani NC, Rebbeck TR, Wani S, Canto MI, Fishman DS, Golan T, Hidalgo M, Kwon RS, Riegert-Johnson DL, Sahani DV, Stoffel EM, Vollmer CM, Al-Haddad MA, Amateau SK, Buxbaum JL, DiMaio CJ, Fujii-Lau LL, Jamil LH, Jue TL, Law JK, Lee JK, Naveed M, Pawa S, Storm AC, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on screening for pancreatic cancer in individuals with genetic susceptibility: methodology and review of evidence. Gastrointest Endosc 2022; 95:827-854.e3. [PMID: 35183359 DOI: 10.1016/j.gie.2021.12.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 12/02/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Mandeep S Sawhney
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Nirav C Thosani
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Timothy R Rebbeck
- Harvard TH Chan School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Marcia I Canto
- Division of Gastroenterology and Hepatology, Johns Hopkins Medicine, Baltimore, Maryland, USA
| | - Douglas S Fishman
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Talia Golan
- Cancer Center, Sheba Medical Center, Yehuda, Israel
| | - Manuel Hidalgo
- Division of Hematology and Oncology, Weill Cornell Medicine, New York, New York, USA
| | - Richard S Kwon
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Douglas L Riegert-Johnson
- Department of Clinical Genomics and Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Dushyant V Sahani
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Elena M Stoffel
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Charles M Vollmer
- Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania, USA
| | - Mohammad A Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Stuart K Amateau
- Division of Gastroenterology Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, California, USA
| | - Christopher J DiMaio
- Department of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA
| | - Larissa L Fujii-Lau
- Department of Gastroenterology, The Queen's Medical Center, Honolulu, Hawaii, USA
| | - Laith H Jamil
- Section of Gastroenterology and Hepatology, Beaumont Health, Royal Oak, Michigan, and Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA
| | - Terry L Jue
- Department of Gastroenterology, The Permanente Medical Group, San Francisco, California, USA
| | - Joanna K Law
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Jeffrey K Lee
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA
| | - Mariam Naveed
- Advent Health Medical Group, Gastroenterology/Hepatology, Advent Health Hospital Altamonte Springs, Altamonte Springs, Florida, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Andrew C Storm
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
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Appelstrand A, Bergstedt F, Elf AK, Fagman H, Hedenström P. Endoscopic ultrasound-guided side-fenestrated needle biopsy sampling is sensitive for pancreatic neuroendocrine tumors but inadequate for tumor grading: a prospective study. Sci Rep 2022; 12:5971. [PMID: 35396490 PMCID: PMC8993931 DOI: 10.1038/s41598-022-09923-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 03/30/2022] [Indexed: 11/10/2022] Open
Abstract
Accurate pretreatment grading of pancreatic neuroendocrine tumors (PanNETs) is important to guide patient management. We aimed to evaluate endoscopic ultrasound-guided fine needle biopsy sampling (EUS-FNB) for the preoperative diagnosis and grading of PanNETs. In a tertiary-center setting, patients with suspected PanNETs were prospectively subjected to 22-gauge, reverse-bevel EUS-FNB. The EUS-FNB samples (Ki-67EUS) and corresponding surgical specimens (Ki-67SURG) were analyzed with Ki-67 indexing and thereafter tumor grading, (GRADEEUS) and (GRADESURG) respectively. In total 52 PanNET-patients [median age: 66 years; females: 25/52; surgical resection 22/52 (42%)] were included. EUS-FNB was diagnostic in 44/52 (85%). In 42 available FNB-slides, the median neoplastic cell count was 1034 (IQR: 504-3667) with 32/42 (76%), 22/42 (52%), and 14/42 (33%) cases exceeding 500, 1000, and 2000 neoplastic cells respectively. Ki-67SURG was significantly higher compared to Ki-67EUS with a moderate correlation comparing Ki-67EUS and Ki-67SURG (Pearson r = 0.60, r2 = 0.36, p = 0.011). The GRADEEUS had a weak level of agreement (κ = 0.08) compared with GRADESURG. Only 2/12 (17%) G2-tumors were correctly graded in EUS-FNB-samples. EUS-guided fine needle biopsy sampling is sensitive for preoperative diagnosis of PanNET but biopsy quality is relatively poor. Therefore, the approach seems suboptimal for pretreatment grading of PanNET.
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Affiliation(s)
- Alexander Appelstrand
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Fredrik Bergstedt
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anna-Karin Elf
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Henrik Fagman
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.,Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Per Hedenström
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. .,Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, Medicinmottagningen, Sahlgrenska Sjukhuset, Blå Stråket 3, 413 35, Gothenburg, Sweden.
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Oh D, Pyo JS, Chung KH, Son BK. The Predicting Role of the Neutrophil-to-Lymphocyte Ratio for the Tumor Grade and Prognosis in Pancreatic Neuroendocrine Tumors. Diagnostics (Basel) 2022; 12:diagnostics12030737. [PMID: 35328291 PMCID: PMC8947579 DOI: 10.3390/diagnostics12030737] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/10/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023] Open
Abstract
This study aims to investigate the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in pancreatic neuroendocrine tumors (PNETs) using meta-analysis. This study evaluates the correlation between the NLR and the prognosis in PNETs from nine eligible studies. In addition, a subgroup analysis based on the tumor grade, treatment, and evaluation criteria, was conducted. The estimated rate of a high NLR was 0.253 (95% confidence interval (CI) 0.198–0.317). The rate of high NLRs was significantly lower in patients with lower tumor grades (G1) than those with higher tumor grades (G2 or G3). In addition, the mean value of the NLR was significantly lower in lower tumor grades than in higher tumor grades. High NLRs were significantly correlated with worse overall and recurrence-free survivals (hazard ratio (HR) 2.180, 95% CI 1.499–3.169 and HR 2.462, 95% CI 1.677–3.615, respectively). In a subgroup analysis, the prognostic implications of the NLR were found in both higher and lower criteria of a high NLR. Taken together, our results show that the NLR could be useful for predicting the tumor grade and the prognosis in PNETs.
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Affiliation(s)
- Dongwook Oh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Jung-Soo Pyo
- Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Korea;
| | - Kwang Hyun Chung
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Korea;
| | - Byoung Kwan Son
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Korea;
- Correspondence:
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Kohno S. Diagnosis and Surgical Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: A Literature Review. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:115-125. [PMID: 35399177 PMCID: PMC8962810 DOI: 10.21873/cdp.10085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 01/31/2022] [Indexed: 06/14/2023]
Abstract
This review aimed to highlight the characteristics and surgical treatments of tumours, and answer questions regarding the assessment of gastrointestinal neuroendocrine neoplasms (NENs) and optimal therapy. NENs comprise tumours that can produce hormones and cause a secretory syndrome. The diagnostic method and accuracy differ depending on the site of occurrence; hence, the relevant scientific society has created NEN treatment guidelines for each organ. Gastroenteric pancreatic (GEP) NENs have been unified and classified together according to the 2019 World Health Organization classification. Treatment is based on complete tumour resection, and when metastatic or primary lesions cannot be completely resected, lesions and symptoms are treated. Except for surgery for NENs, chemotherapy, molecularly targeted drugs, transarterial chemoembolization, etc., have also been confirmed as treatments. GEP NEN treatment methods will continue to advance and change because of surgery and other advances in treatment and diagnostic methods.
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Affiliation(s)
- Shuzo Kohno
- Department of Surgery, The Jikei University Katsushika Medical Center, Tokyo, Japan
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Atri M, Jang HJ, Kim TK, Khalili K. Contrast-enhanced US of the Liver and Kidney: A Problem-solving Modality. Radiology 2022; 303:11-25. [PMID: 35191740 DOI: 10.1148/radiol.211347] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Contrast-enhanced US (CEUS) has an important role as a supplement to CT or MRI in clinical practice. The main established utilizations are in the liver and the kidney. The primary advantages of CEUS compared with contrast-enhanced CT or MRI relate to its superior contrast resolution, real-time continuous scanning, pure intravascular nature, portability, and safety-especially in patients with renal impairment or CT or MRI contrast agent allergy. This article focuses on the use of CEUS in the liver and kidney.
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Affiliation(s)
- Mostafa Atri
- From the Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Women's College Hospital, University of Toronto, Toronto General Hospital, 585 University Ave, Toronto, ON, Canada M5G 2N2
| | - Hyun-Jung Jang
- From the Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Women's College Hospital, University of Toronto, Toronto General Hospital, 585 University Ave, Toronto, ON, Canada M5G 2N2
| | - Tae Kyoung Kim
- From the Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Women's College Hospital, University of Toronto, Toronto General Hospital, 585 University Ave, Toronto, ON, Canada M5G 2N2
| | - Korosh Khalili
- From the Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Women's College Hospital, University of Toronto, Toronto General Hospital, 585 University Ave, Toronto, ON, Canada M5G 2N2
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Marchese U, Gaillard M, Pellat A, Tzedakis S, Abou Ali E, Dohan A, Barat M, Soyer P, Fuks D, Coriat R. Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2022; 14:433. [PMID: 35053593 PMCID: PMC8773540 DOI: 10.3390/cancers14020433] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/13/2022] Open
Abstract
Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.
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Affiliation(s)
- Ugo Marchese
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Martin Gaillard
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Anna Pellat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
| | - Stylianos Tzedakis
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
| | - Anthony Dohan
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - Maxime Barat
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - Philippe Soyer
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - David Fuks
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Romain Coriat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
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Trends in Incidence and Survival of Patients with Pancreatic Neuroendocrine Neoplasm, 1987-2016. JOURNAL OF ONCOLOGY 2022; 2021:4302675. [PMID: 34976056 PMCID: PMC8716229 DOI: 10.1155/2021/4302675] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 11/11/2021] [Indexed: 01/27/2023]
Abstract
Background Pancreatic neuroendocrine neoplasm (pNEN), with the lowest 5-year survival rates in neuroendocrine tumors (NETs), exerts great threat to human health. Because large-scale population research aimed at pNEN is rare, we aimed to explore the tendencies and differences of changes in incidences and survival rates of pNEN in each decade from 1987 to 2016 and evaluate the impacts of age, sex, race, socioeconomic status (SES), and grade. Methods Data on pNEN cases from 1987 to 2016 were extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier, Cox proportional hazards regression analyses, and relative survival rates (RSRs) were used to identify risk factors for pNEN. Results The incidence and survival duration of pNEN increase every decade due to medical developments. The disparities of long-term survival in different age, sex, and grade groups expanded over time while that in race and SES groups narrowed. Older age and higher grade are independent risk factors for poorer survival. Females have lower incidence and longer survival than males. Prognosis of Black patients and poor (medium and high poverty) patients improved. Conclusions This study depicted changes in incidence and survival rates of pNEN over the past three decades and evaluated potential risk factors related to pNEN, benefiting future prediction of vulnerable and clinical options.
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Turla A, Zamparini M, Milione M, Grisanti S, Amoroso V, Pedersini R, Cosentini D, Berruti A. Ovarian Strumal Carcinoid: Case Report, Systematic Literature Review and Pooled Analysis. Front Endocrinol (Lausanne) 2022; 13:871210. [PMID: 35528006 PMCID: PMC9069053 DOI: 10.3389/fendo.2022.871210] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 03/24/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy, however, cases with metastatic disease have been described. No data in the literature are available to guide diagnosis and therapy. METHODS We performed a pooled analysis and a systematic review of histopathological-confirmed strumal carcinoid cases published in the literature using the following keywords: "strumal carcinoid of the ovary", "strumal carcinoid case report". A case of strumal carcinoid tumor diagnosed and followed-up at the Medical Oncology Unit of Spedali Civili (Brescia, Italy) was also described and included. RESULTS Sixty-six eligible publications were identified, providing data from one hundred and seventeen patients, plus a case diagnosed at our institution. At presentation, among the eighty-eight patients with symptomatic disease, 37% of patients suffered from abdominal distention and 49% from pain due to a growing abdominal tumor mass, 37% from constipation (peptide YY was analyzed in only nine of them, resulting above the physiologic range). Surgery was the primary therapy in 99% of the patients. Three patients had metastatic disease at diagnosis and five patients underwent recurrence after radical surgery. Histology at disease recurrence concerned the thyroid component in two patients, the carcinoid component in two patients, both histologies in one patient. Median disease-free survival and overall survival in this series were not attained. CONCLUSION Strumal carcinoid of the ovary generally presents a benign behavior and surgery is curative in most cases. However, a small group of patients with this disease can undergo disease recurrence due to both the thyroid and the neuroendocrine (carcinoid) components. A follow-up in radically operated patients is therefore needed, particularly in those with a voluminous disease at diagnosis.
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Affiliation(s)
- Antonella Turla
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
| | - Manuel Zamparini
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
| | - Massimo Milione
- 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy
| | - Salvatore Grisanti
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
| | - Vito Amoroso
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
| | - Rebecca Pedersini
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
| | - Deborah Cosentini
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
| | - Alfredo Berruti
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy
- *Correspondence: Alfredo Berruti,
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