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Mo S, Huang C, Wang Y, Qin S. Endoscopic ultrasonography-based intratumoral and peritumoral machine learning ultrasomics model for predicting the pathological grading of pancreatic neuroendocrine tumors. BMC Med Imaging 2025; 25:22. [PMID: 39827128 PMCID: PMC11743008 DOI: 10.1186/s12880-025-01555-x] [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: 03/25/2024] [Accepted: 01/03/2025] [Indexed: 01/22/2025] Open
Abstract
OBJECTIVES The objective is to develop and validate intratumoral and peritumoral ultrasomics models utilizing endoscopic ultrasonography (EUS) to predict pathological grading in pancreatic neuroendocrine tumors (PNETs). METHODS Eighty-one patients, including 51 with grade 1 PNETs and 30 with grade 2/3 PNETs, were included in this retrospective study after confirmation through pathological examination. The patients were randomly allocated to the training or test group in a 6:4 ratio. Univariate and multivariate logistic regression were used for screening clinical and ultrasonic characteristics. Ultrasomics is ultrasound-based radiomics. Ultrasomics features were extracted from both the intratumoral and peritumoral regions of conventional EUS images. Subsequently, the dimensionality of these radiomics features was reduced using the least absolute shrinkage and selection operator (LASSO) algorithm. A machine learning algorithm, namely multilayer perception (MLP), was employed to construct prediction models using only the nonzero coefficient features and retained clinical features, respectively. RESULTS One hundred seven ultrasomics features based on EUS were extracted, and only features with nonzero coefficients were ultimately retained. Among all the models, the combined ultrasomics model achieved the greatest performance, with an AUC of 0.858 (95% CI, 0.7512 - 0.9642) in the training group and 0.842 (95% CI, 0.7061 - 0.9785) in the test group. A calibration curve and a decision curve analysis (DCA) also demonstrated its accuracy and utility. CONCLUSIONS The integrated model using EUS ultrasomics features from intratumoral and peritumoral tumors accurately predicts PNETs' pathological grades pre-surgery, aiding personalized treatment planning. TRIAL REGISTRATION ChiCTR2400091906.
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Affiliation(s)
- Shuangyang Mo
- Gastroenterology Department/Clinical Nutrition Department, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, China
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Cheng Huang
- Oncology Department, Liuzhou Peoples' Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Yingwei Wang
- Gastroenterology Department/Clinical Nutrition Department, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Shanyu Qin
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
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Bispo M, Marques S, Fernandes A, Rodrigues-Pinto E, Vilas-Boas F, Rio-Tinto R, Devière J. Portuguese Pancreatic Club Perspective on the Surveillance Strategy for Pancreatic Neuroendocrine Tumours: When and How to Do It? GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:306-313. [PMID: 39360175 PMCID: PMC11444664 DOI: 10.1159/000535815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 11/24/2023] [Indexed: 10/04/2024]
Abstract
Background Pancreatic neuroendocrine tumours (pNETs) are a highly heterogeneous group of tumours with widely variable biological behaviour. The incidence of pNETs has risen exponentially over the last three decades, particularly for asymptomatic small pNETs (≤2 cm), due to the widespread use of cross-sectional imaging in clinical practice. Summary Current consensus guidelines suggest that incidentally discovered pNETs ≤2 cm can be selectively followed due to the overall low risk of malignancy. Nevertheless, the "watch-and-wait" management strategy for small asymptomatic pNETs is still not widely accepted due to the lack of long-term data on the natural history of these small lesions. Additionally, it is clear that a subset of small pNETs may show malignant behaviour. Key Message Given the non-negligible risk of malignancy even in small pNETs, it is of the utmost importance to identify other preoperative factors, other than size, that may help to stratify the risk of malignant behaviour and guide clinical management. In this article, the Portuguese Pancreatic Club reviews the importance of risk stratification of pNETs and presents an updated perspective on the surveillance strategy for sporadic well-differentiated pNETs.
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Affiliation(s)
- Miguel Bispo
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Susana Marques
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Alexandra Fernandes
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Eduardo Rodrigues-Pinto
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Filipe Vilas-Boas
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | | | - Jacques Devière
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme University Hospital – Université Libre de Bruxelles, Brussels, Belgium
| | - on behalf of the Portuguese Pancreatic Club, specialized section of the Portuguese Society of Gastroenterology
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme University Hospital – Université Libre de Bruxelles, Brussels, Belgium
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Eren OC, Bagci P, Balci S, Ohike N, Saka B, Sokmensuer C, Leblebici CB, Xue Y, Reid MD, Krasinskas AM, Kooby D, Maithel SK, Sarmiento J, Cheng JD, Taskin OC, Kapran Y, Tarcan ZC, Luchini C, Scarpa A, Basturk O, Adsay NV. Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols. Ann Surg Oncol 2024; 31:7001-7011. [PMID: 38955993 PMCID: PMC11413052 DOI: 10.1245/s10434-024-15632-y] [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: 04/18/2023] [Accepted: 06/05/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Grade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach. METHODS Ki67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed. RESULTS In initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001). CONCLUSIONS G2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.
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Affiliation(s)
- Ozgur Can Eren
- Department of Pathology, Koç University, Koç University Hospital, Istanbul, Türkiye
| | - Pelin Bagci
- Department of Pathology, Marmara University, Istanbul, Türkiye
| | - Serdar Balci
- Department of Pathology, Memorial Sisli Hospital, Istanbul, Türkiye
| | - Nobuyuki Ohike
- Department of Pathology, St. Marianna University, Kawasaki, Kanagawa, Japan
| | - Burcu Saka
- Department of Pathology, Koç University, Koç University Hospital, Istanbul, Türkiye
| | - Cenk Sokmensuer
- Department of Pathology, Hacettepe University, Ankara, Türkiye
| | | | - Yue Xue
- Department of Pathology, Northwestern University, Evanston, IL, USA
| | | | | | - David Kooby
- Department of Surgery, Emory University, Atlanta, GA, USA
| | | | - Juan Sarmiento
- Department of Surgery, Emory University, Atlanta, GA, USA
| | | | - Orhun Cig Taskin
- Department of Pathology, Koç University, Koç University Hospital, Istanbul, Türkiye
| | - Yersu Kapran
- Department of Pathology, Koç University, Koç University Hospital, Istanbul, Türkiye
| | - Zeynep Cagla Tarcan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology and ARC-Net Research Centre, University of Verona, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology and ARC-Net Research Centre, University of Verona, Verona, Italy
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - N Volkan Adsay
- Department of Pathology, Koç University, Koç University Hospital, Istanbul, Türkiye.
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Holzer K, Bartsch DK. [Gastroenteropancreatic neuroendocrine neoplasms-Surgery in a multimodal concept]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:773-782. [PMID: 38935138 DOI: 10.1007/s00104-024-02117-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/28/2024]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are mainly found in the small intestine and pancreas. The course of the disease in patients is highly variable and depends on the degree of differentiation (G1-G3) of the neoplasm. The potential for metastasis formation of GEP-NEN is high even with good differentiation (G1). Lymph node metastases and, in many cases, liver metastases are also often found. Less common are bone metastases or peritoneal carcinomas. The treatment of these GEP-NENs is surgical, whenever possible. If an R0 resection with removal of all lymph node and liver metastases is successful, the prognosis of the patients is excellent. Patients with diffuse liver or bone metastases can no longer be cured by surgery alone. The long-term survival of these patients is nowadays possible due to the availability of drugs (e.g., somatostatin analogues, tyrosine kinase inhibitors), peptide receptor radionuclide therapy (PRRT) and liver-directed procedures, with a good quality of life.
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Affiliation(s)
- K Holzer
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Marburg, Baldingerstraße, Marburg, Deutschland.
| | - D K Bartsch
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Marburg, Baldingerstraße, Marburg, Deutschland
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Mo S, Huang C, Wang Y, Zhao H, Wu W, Jiang H, Qin S. Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors. Front Endocrinol (Lausanne) 2024; 15:1383814. [PMID: 38952387 PMCID: PMC11215175 DOI: 10.3389/fendo.2024.1383814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 06/05/2024] [Indexed: 07/03/2024] Open
Abstract
Objectives To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs). Methods A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed. Results A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts. Conclusion A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.
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Affiliation(s)
- Shuangyang Mo
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Cheng Huang
- Oncology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Yingwei Wang
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Huaying Zhao
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Wenhong Wu
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Haixing Jiang
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Shanyu Qin
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Chouchane A, Kirchner P, Marinoni I, Sticová E, Jirásek T, Perren A. Pancreatic Neuroendocrine Microtumors (WHO 2022) Are Not Always Low-Grade Neoplasms: A Case with a Highly Increased Proliferation Rate. Endocr Pathol 2024; 35:147-153. [PMID: 38403790 PMCID: PMC11176210 DOI: 10.1007/s12022-024-09802-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/31/2024] [Indexed: 02/27/2024]
Abstract
Traditionally considered non-functional low proliferative benign neuroendocrine proliferations measuring less than 5 mm, pancreatic (neuro)endocrine microadenomas are now classified as pancreatic neuroendocrine microtumors in the 2022 WHO classification of endocrine and neuroendocrine tumors. This case report discussed the features of an incidentally identified 4.7-mm glucagon-expressing pancreatic neuroendocrine microtumor with MEN1 mutation only, chromosomally stable and an epigenetic alpha-like phenotype. The tumor was associated with an unexplained increased proliferation rate in Ki-67 of 15%. There was no associated DAXX/ATRX deficiency. The presented case challenges the conventional thought of a low proliferative disease of the so-called "pancreatic neuroendocrine microadenomas" and provides additional support to the 2022 WHO classification that also requires grading of these neoplasms. Despite exhibiting molecular features of less aggressive behavior, the case also underscores the biological complexity of pancreatic neuroendocrine microtumors. By recognizing the heterogenous spectrum of neuroendocrine neoplasms, the current case also contributes to ongoing discussions on how to optimize the clinical management of such tumors.
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Affiliation(s)
- Aziz Chouchane
- Institute For Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Philipp Kirchner
- Institute For Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Ilaria Marinoni
- Institute For Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Eva Sticová
- Clinical and Transplant Pathology Centre, Institute of Clinical and Experimental Medicine, Prague, Czech Republic
| | - Tomáš Jirásek
- Department of Pathology, Liberec Regional Hospital, Liberec, Czech Republic
| | - Aurel Perren
- Institute For Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
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Massironi S. The diagnostic challenges of functioning neuroendocrine tumors: balancing accuracy, availability, and personalized care. Expert Rev Endocrinol Metab 2024; 19:99-101. [PMID: 38390719 DOI: 10.1080/17446651.2024.2320639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 02/15/2024] [Indexed: 02/24/2024]
Affiliation(s)
- Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, School of Medicine, Monza, Italy
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Regolo M, Cardaci N, Salmeri C, Laudani A, Colaci M, Ippolito M, Motta F, Magrì S, Parisi S, Torcitto AG, Malatino L. Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review. J Clin Med 2023; 12:6617. [PMID: 37892755 PMCID: PMC10607714 DOI: 10.3390/jcm12206617] [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: 09/14/2023] [Revised: 09/24/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.
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Affiliation(s)
- Matteo Regolo
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Nicolas Cardaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Clara Salmeri
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Alfredo Laudani
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Michele Colaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Massimo Ippolito
- Nuclear Medicine Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Fabio Motta
- Pathological Anatomy Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Salvatore Magrì
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | - Stefanie Parisi
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | | | - Lorenzo Malatino
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
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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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10
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Standring O, Benitez Sanchez S, Pasha S, Demyan L, Lad N, Ruff SM, Anantha S, Karpeh M, Newman E, Nealon W, Talamini M, Coppa G, Deutsch G, Weiss M, DePeralta DK. Potential Role for Observation in Small Solid Pseudopapillary Neoplasm (SPN). Ann Surg Oncol 2023; 30:5105-5112. [PMID: 37233954 DOI: 10.1245/s10434-023-13496-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 03/28/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Solid pseudopapillary neoplasms (SPN) are rare tumors of the pancreas, typically affecting young women. Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. We explore the idea that small, localized SPN could be safely observed. METHODS This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code 8452. RESULTS A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. CONCLUSIONS Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.
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Affiliation(s)
- Oliver Standring
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
| | | | - Shamsher Pasha
- Northwell Health Cancer Institute, Lake Success, NY, USA
| | - Lyudmyla Demyan
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
| | - Neha Lad
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
- Northwell Health Cancer Institute, Lake Success, NY, USA
| | - Samantha M Ruff
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
| | - Sandeep Anantha
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Martin Karpeh
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Surgical Oncology, Northwell Health, Huntington Hospital, Huntington, NY, USA
| | - Elliot Newman
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Surgical Oncology, Northwell Health, Lenox Hill Hospital, New York, NY, USA
| | - William Nealon
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Mark Talamini
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Gene Coppa
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Gary Deutsch
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Matthew Weiss
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA
- Northwell Health Cancer Institute, Lake Success, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Danielle K DePeralta
- Northwell Health, North Shore/Long Island Jewish General Surgery, Manhasset, NY, USA.
- Northwell Health Cancer Institute, Lake Success, NY, USA.
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
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11
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Bolm L, Nebbia M, Wei AC, Zureikat AH, Fernández-del Castillo C, Zheng J, Pulvirenti A, Javed AA, Sekigami Y, Petruch N, Qadan M, Lillemoe KD, He J, Ferrone CR. Response to Commentary on '"Long-Term Outcomes of Parenchyma-Sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort". ANNALS OF SURGERY OPEN 2023; 4:e277. [PMID: 37601459 PMCID: PMC10431566 DOI: 10.1097/as9.0000000000000277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 03/04/2023] [Indexed: 08/22/2023] Open
Affiliation(s)
- Louisa Bolm
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Martina Nebbia
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Alice C. Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H. Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Jian Zheng
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Ammar A. Javed
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD
| | - Yurie Sekigami
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Natalie Petruch
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Motaz Qadan
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Keith D. Lillemoe
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Jin He
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD
| | - Cristina R. Ferrone
- From the Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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12
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Sulciner ML, Clancy TE. Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2023; 15:2006. [PMID: 37046665 PMCID: PMC10093271 DOI: 10.3390/cancers15072006] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones. A wide range of clinical behavior can be seen, with the primary prognostic indicator being tumor grade as defined by the Ki67 proliferation index and mitotic index. Surgery is the primary treatment modality for PNETs. While functional PNETs should undergo resection for symptom control as well as potential curative intent, nonfunctional PNETs are increasingly managed nonoperatively. There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance. Evidence supports surgical management of metastatic disease if possible, and occasionally even surgical management of the primary tumor in the setting of widespread metastases. In this review, we highlight the evolving surgical management of local and metastatic PNETs.
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Affiliation(s)
| | - Thomas E. Clancy
- Division of Surgical Oncology, Department of Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
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13
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Zhang WH, Xu JF, Hu YH, Qin Y, Chen J, Yu XJ, Xu XW, Ji SR. The Surgical and Therapeutic Activities of Non-Functional Pancreatic Neuroendocrine Tumors at a High-Volume Institution. Cancers (Basel) 2023; 15:cancers15071955. [PMID: 37046616 PMCID: PMC10093673 DOI: 10.3390/cancers15071955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND This study aimed to summarize the surgical and therapeutic activities of non-functional pancreatic neuroendocrine tumors (NF-PanNETs) and perform survival analyses of a 15-year single-institutional cohort of NF-PanNETs. METHODS In total, 1001 patients with neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 509 patients with NF-PanNETs from 2006 to 2020 were included. For time trend analyses, the 15-year study period was randomly divided into three periods. Survival analyses used the Kaplan-Meier method and Cox regression models. RESULTS The total number of resected NF-PanNETs increased over the 15-year study period, from 5 resections in 2006 to 94 resections in 2020. A significant decrease in the tumor size was observed, from a mean of 4.0 cm to 3.3 cm, and to 3.0 cm in the most recent period (p = 0.006). Minimally invasive techniques gradually increased from 3.5% to 12.9%, and finally to 46.4% in the most recent period (p < 0.001). In non-metastatic and resected tumors, the tumor size (p < 0.001), positive lymph node (p < 0.001), adjuvant treatment (p = 0.048), and tumor grade (p < 0.001) were independent prognostic factors for recurrence-free survival (RFS). The microvascular invasion (p = 0.024) and tumor grade (p = 0.013) were independent prognostic factors for overall survival (OS). A malignant transformation from NET into neuroendocrine carcinoma was observed. CONCLUSIONS An increasing number of NF-PanNETs resection and minimally invasive surgery was shown. In non-metastatic and resected tumors NF-PanNETs, tumor size, positive lymph node, adjuvant treatment, and tumor grade were independent predictors of RFS. Microvascular invasion and tumor grade were independent prognostic factors for OS.
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Affiliation(s)
- Wu-Hu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jun-Feng Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yu-Heng Hu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xiao-Wu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Shun-Rong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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14
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Nanno Y, Toyama H, Matsumoto I, Uemura J, Asari S, Goto T, Lee D, Murakami T, Komatsu S, Yanagimoto H, Kido M, Ajiki T, Okano K, Takeyama Y, Fukumoto T. Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2023; 30:3493-3500. [PMID: 36795254 DOI: 10.1245/s10434-023-13193-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 01/14/2023] [Indexed: 02/17/2023]
Abstract
BACKGROUND Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.
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Affiliation(s)
- Yoshihide Nanno
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hirochika Toyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Ippei Matsumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
| | - Jun Uemura
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Sadaki Asari
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tadahiro Goto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Dongha Lee
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
| | - Tomomasa Murakami
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Shohei Komatsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hiroaki Yanagimoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masahiro Kido
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tetsuo Ajiki
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Yoshifumi Takeyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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15
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Rimbaş M, Rizzatti G, Tosoni A, Impagnatiello M, Panzuto F, Larghi A. Small nonfunctional pancreatic neuroendocrine neoplasms: Time for a step-up treatment approach? Endosc Ultrasound 2023; 12:1-7. [PMID: 36510866 PMCID: PMC10134916 DOI: 10.4103/eus-d-22-00028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Surgery has been regarded as the only curative treatment for patients with small nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) less than 2 cm. Due to the significant adverse event rates of surgery, the European Neuroendocrine Tumor Society issued guidelines favoring surveillance for those patients lacking criteria suggestive of an aggressive disease. Despite the above recommendations, a significant proportion of small NF-PNEN patients still undergo surgery. Recently, several studies have reported the safety and effectiveness of EUS-guided radiofrequency ablation (RFA) for the treatment of small NF-PNENs. The experience with EUS-RFA is, however, limited, but published results indicate a potential role as a minimally invasive alternative treatment for these patients, in particular in those in whom further progression is more probable, before they reach the absolute need for surgery. A step-up approach with EUS-RFA followed by surgery for the failure cases can become a valid option to be validated in clinical studies.
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Affiliation(s)
- Mihai Rimbaş
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Gastroenterology, Colentina Clinical Hospital; Department of Internal Medicine, Carol Davila University of Medicine, Bucharest, Romania
| | - Gianenerico Rizzatti
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alberto Tosoni
- Department of Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Michele Impagnatiello
- Department of Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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16
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Ptasnuka M, Truskovs A, Ozolins A, Narbuts Z, Sperga M, Plaudis H. Sporadic pancreatic neuroendocrine neoplasms: A retrospective clinicopathological and outcome analysis from a Latvian study group. Front Surg 2023; 10:1131333. [PMID: 37021091 PMCID: PMC10069647 DOI: 10.3389/fsurg.2023.1131333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 03/03/2023] [Indexed: 04/07/2023] Open
Abstract
Background Although pancreatic neuroendocrine neoplasms (PNEN) are rare, there has been a constant increase in incidence. Furthermore, PNEN present unique clinical behaviors and long-term survival can be expected even in the presence of metastases as compared with ductal adenocarcinoma of the pancreas. Determining the best therapeutic approach and proper timing of therapy requires knowledge of reliable prognostic factors. Therefore, the aim of this study was to explore clinicopathological features, treatment, and survival outcomes of patients with PNEN based on Latvian gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) registry data. Method Patients with confirmed PNEN at Riga East Clinical University Hospital and Pauls Stradins Clinical University Hospital, between 2008 and 2020, were retrospectively analyzed. Data were collected and included in EUROCRINE, an open-label international endocrine surgical registry. Results In total, 105 patients were included. The median age at diagnosis was 64 years (IQR 53.0-70.0) for males and 61 years (IQR 52.5-69.0) for females. In 77.1% of patients, tumors were hormonally nonfunctional. Among those with functioning PNEN, 10.5% of patients presented with hypoglycemia and were diagnosed with insulinoma, 6.7% of patients presented with symptoms related to carcinoid syndrome; 30.5% of patients showed distant metastases at the time of diagnosis, and surgery was performed in 67.6% of patients. Notably, for five patients with nonfunctional PNEN <2 cm, a "watch and wait" approach was used; none of the patients developed metastatic disease. The median length of hospital stay was 8 days (IQR 5-13). Major postoperative complications were found in 7.0% of patients, and reoperation was conducted for 4.2% of patients, due to postpancreatectomy bleeding (2/71) and abdominal collection (1/71). The median follow-up period was 34 months (IQR 15.0-68.8). The OS at the last follow-up was 75.2% (79/105). The observed 1-, 5- and 10-year survival rates were 87.0, 71.2 and 58.0, respectively. Seven of the surgically treated patients had tumor recurrence. The median time of recurrence was 39 months (IQR 19.0-95.0). A univariable Cox proportional hazard analysis provided evidence that a nonfunctional tumor, a larger tumor size, the presence of distant metastases, a higher tumor grade, and the tumor stage were strong, negative predictors of OS. Conclusion Our study represents the general trends of clinicopathological features and treatment of PNEN in Latvia. For PNEN patients, tumor functionality, size, distant metastases, grade, and stage may be useful to predict OS and must be confirmed in further studies. Furthermore, a "surveillance" strategy might be safe for selected patients with small asymptomatic PNEN.
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Affiliation(s)
- Margarita Ptasnuka
- Department of General and Emergency Surgery, Riga East Clinical University Hospital, Riga, Latvia
- Correspondence: Margarita Ptasnuka
| | - Arturs Truskovs
- Department of Surgery, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
- Department of Surgery, Riga Stradiņš University, Riga, Latvia
| | - Arturs Ozolins
- Department of Surgery, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
- Department of Surgery, Riga Stradiņš University, Riga, Latvia
| | - Zenons Narbuts
- Department of Surgery, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
- Department of Surgery, Riga Stradiņš University, Riga, Latvia
| | - Maris Sperga
- Department of Surgery, Riga Stradiņš University, Riga, Latvia
- Department of Infectious Pathology, Pathology Center, Riga, Latvia
| | - Haralds Plaudis
- Department of General and Emergency Surgery, Riga East Clinical University Hospital, Riga, Latvia
- Department of Surgery, Riga Stradiņš University, Riga, Latvia
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17
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Klaiber U, Stättner S. Current standards in the surgical treatment of pancreatic and small intestinal neuroendocrine tumors. MEMO - MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2022. [DOI: 10.1007/s12254-022-00840-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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18
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Partelli S, Massironi S, Zerbi A, Niccoli P, Kwon W, Landoni L, Panzuto F, Tomazic A, Bongiovanni A, Kaltsas G, Sauvanet A, Bertani E, Mazzaferro V, Caplin M, Armstrong T, Weickert MO, Ramage J, Segelov E, Butturini G, Staettner S, Cives M, Frilling A, Moulton CA, He J, Boesch F, Selberheer A, Twito O, Castaldi A, De Angelis CG, Gaujoux S, Holzer K, Wilson CH, Almeamar H, Vigia E, Muffatti F, Lucà M, Lania A, Ewald J, Kim H, Salvia R, Rinzivillo M, Smid A, Gardini A, Tsoli M, Hentic O, Colombo S, Citterio D, Toumpanakis C, Ramsey E, Randeva HS, Srirajaskanthan R, Croagh D, Regi P, Gasteiger S, Invernizzi P, Ridolfi C, Giovannini M, Jang JY, Bassi C, Falconi M. Management of asymptomatic sporadic non-functioning pancreatic neuroendocrine neoplasms no larger than 2 cm: interim analysis of prospective ASPEN trial. Br J Surg 2022; 109:1186-1190. [PMID: 35986682 PMCID: PMC10364756 DOI: 10.1093/bjs/znac267] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/18/2022] [Accepted: 07/14/2022] [Indexed: 12/31/2022]
Affiliation(s)
- Stefano Partelli
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.,Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sara Massironi
- Division of Gastroenterology and Centre for Autoimmune Liver Diseases, San Gerardo Hospital, Monza, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Patricia Niccoli
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Luca Landoni
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, ENETS Centre of Excellence, Sant' Andrea University Hospital, Rome, Italy
| | - Ales Tomazic
- Department of Abdominal Surgery, University Medical Centre, Ljubijana, Slovenia
| | - Alberto Bongiovanni
- Osteoncology and Rare Tumours Centre (CDO-TR), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - Gregory Kaltsas
- First Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Alain Sauvanet
- Department of Pancreatology, Hôpital Beaujon, University of Paris, Paris, France
| | - Emilio Bertani
- Division of Gastrointestinal Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Martyn Caplin
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Thomas Armstrong
- Department of Hepatobiliary Surgery, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton, Southampton, UK
| | - Martin O Weickert
- ARDEN NET Centre, ENETS Centre of Excellence, University Hospitals Coventry and Warwickshire NHS Trust and Warwick Medical School, University of Warwick, Coventry, UK
| | - John Ramage
- Kings Health Partners NET Centre, Kings College Hospital London, London, UK
| | - Eva Segelov
- Department of Oncology and Surgery (School of Clinical Sciences at Monash Health), Monash University, Clayton, Victoria, Australia
| | | | - Stefan Staettner
- Department of General, Visceral and Vascular Surgery, Salzkammergutklinikum Vöcklabruck, Vöcklabruck, Austria
| | - Mauro Cives
- Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Carol Anne Moulton
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.,Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medical, Baltimore, Maryland, USA
| | - Florian Boesch
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Andreas Selberheer
- Section Endocrine Surgery, Division of General Surgery, Department of Surgery, Medical University, Vienna, Austria
| | - Orit Twito
- Endocrine Institute, Meir Medical Center, Kfar-Sava, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Antonio Castaldi
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Claudio G De Angelis
- Gastroenterology Unit, Department of Medical Sciences, City of Health and Science Hospital, Turin, Italy
| | - Sebastien Gaujoux
- Department of Digestive, Hepatobiliary and Endocrine Surgery, Paris Sorbonne University, Pitiè Salpétrière Hospital, Paris, France
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Section of Endocrine Surgery, University Hospital Marburg (UKGM), Marburg, Germany
| | - Colin H Wilson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Hussein Almeamar
- National NET Centre and ENETS Centre of Excellence, St Vincent's University Hospital, Dublin, Ireland
| | - Emanuel Vigia
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, CHULC, Lisbon, Portugal
| | - Francesca Muffatti
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.,Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Martina Lucà
- Division of Gastroenterology and Centre for Autoimmune Liver Diseases, San Gerardo Hospital, Monza, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Andrea Lania
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Jacques Ewald
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, ENETS Centre of Excellence, Sant' Andrea University Hospital, Rome, Italy
| | - Alojz Smid
- Department of Gastroenterology and Hepatology, University Medical Centre Ljubijana, Ljubljana, Slovenia
| | - Andrea Gardini
- General and Oncological Surgery Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Marina Tsoli
- First Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Olivia Hentic
- Department of Pancreatology, Hôpital Beaujon, University of Paris, Paris, France
| | - Samuele Colombo
- Division of Gastrointestinal Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Davide Citterio
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Christos Toumpanakis
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Emma Ramsey
- Department of Hepatobiliary Surgery, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton, Southampton, UK
| | | | | | - Daniel Croagh
- Department of Oncology and Surgery (School of Clinical Sciences at Monash Health), Monash University, Clayton, Victoria, Australia
| | - Paolo Regi
- Department of Surgery, Pederzoli Hospital, Peschiera del Garda, Italy
| | - Silvia Gasteiger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Pietro Invernizzi
- Division of Gastroenterology and Centre for Autoimmune Liver Diseases, San Gerardo Hospital, Monza, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Cristina Ridolfi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Hospital-IRCCS, Rozzano, Milan, Italy
| | - Marc Giovannini
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Massimo Falconi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.,Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
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19
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Bolm L, Nebbia M, Wei AC, Zureikat AH, Fernández-del Castillo C, Zheng J, Pulvirenti A, Javed AA, Sekigami Y, Petruch N, Qadan M, Lillemoe KD, He J, Ferrone CR. Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort. Ann Surg 2022; 276:522-531. [PMID: 35758433 PMCID: PMC9388557 DOI: 10.1097/sla.0000000000005559] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
INTRODUCTION The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3 cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections. METHODS Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model. RESULTS Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5 cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P <0.001), had less intraoperative blood loss (358 vs 511 ml, P <0.001) and had shorter operative times (180 vs 330 minutes, P <0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P <0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P <0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy. CONCLUSION In small <3 cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.
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Affiliation(s)
- Louisa Bolm
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Martina Nebbia
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Alice C. Wei
- (2) Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H. Zureikat
- (3) Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Jian Zheng
- (3) Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Ammar A. Javed
- (4) Department of Surgery, Johns Hopkins Hospital, Baltimore, MD
| | - Yurie Sekigami
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Natalie Petruch
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Motaz Qadan
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Keith D. Lillemoe
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Jin He
- (4) Department of Surgery, Johns Hopkins Hospital, Baltimore, MD
| | - Cristina R. Ferrone
- (1) Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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20
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Hackeng WM, Assi HA, Westerbeke FHM, Brosens LAA, Heaphy CM. Prognostic and Predictive Biomarkers for Pancreatic Neuroendocrine Tumors. Surg Pathol Clin 2022; 15:541-554. [PMID: 36049835 DOI: 10.1016/j.path.2022.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Pancreatic neuroendocrine tumors (PanNETs) represent a clinically challenging disease because these tumors vary in clinical presentation, natural history, and prognosis. Novel prognostic biomarkers are needed to improve patient stratification and treatment options. Several putative prognostic and/or predictive biomarkers (eg, alternative lengthening of telomeres, alpha-thalassemia/mental retardation, X-linked (ATRX)/Death Domain Associated Protein (DAXX) loss) have been independently validated. Additionally, recent transcriptomic and epigenetic studies focusing on endocrine differentiation have identified PanNET subtypes that display similarities to either α-cells or β-cells and differ in clinical outcomes. Thus, future prospective studies that incorporate genomic and epigenetic biomarkers are warranted and have translational potential for individualized therapeutic and surveillance strategies.
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Affiliation(s)
- Wenzel M Hackeng
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
| | - Hussein A Assi
- Department of Medicine, Boston University School of Medicine, 820 Harrison Avenue, FGH 2011, Boston, MA 02118, USA
| | - Florine H M Westerbeke
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
| | - Christopher M Heaphy
- Department of Medicine, Boston University School of Medicine, 650 Albany Street, Room 444, Boston, MA 02118, USA; Department of Pathology & Laboratory Medicine, Boston University School of Medicine, 650 Albany Street, Room 444, Boston, MA 02118, USA.
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21
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Wiese D, Bartsch DK. [Controversy: asymptomatic small pancreatic neuroendocrine neoplasms : Current standards in diagnostics and treatment]. CHIRURGIE (HEIDELBERG, GERMANY) 2022; 93:739-744. [PMID: 35913627 DOI: 10.1007/s00104-022-01647-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/20/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND For the increasingly diagnosed entity of small asymptomatic, sporadic, nonfunctional, pancreatic neuroendocrine neoplasms (pNEN), a negligible or at least unclear prognostic relevance of the disease for patient survival has often been observed. OBJECTIVE Safety and acceptance of a watch-and-wait strategy versus surgical resection for small, asymptomatic nonfunctional (NF) pNEN. METHODS Presentation and evaluation of the relevant literature as well as the corresponding national and European guidelines. RESULTS Surgery of small NF-pNEN shows complication rates of 15-32% (Clavien-Dindo ≥ 3) and a mortality of 3.6%. Even for pNEN < 2 cm the presence of lymph node metastases has been observed in 11% of cases, while their prognostic relevance in G1-pNEN compared with active surveillance remains unclear. On average 14% of patients under active surveillance for small NF-pNEN, underwent a resection. Relevant tumor growth during surveillance was found in < 20% of cases. In all well-selected surveillance cohorts no metachronous lymphatic or distant metastases occurred during active surveillance and especially no cases of a metachronous no longer curable disease. CONCLUSION Even small asymptomatic NF-pNEN have a certain metastatic potential but the clinical relevance has prospectively not yet been clearly determined. Controlled surveillance of these tumors is at least an alternative to immediate tumor resection. Especially patients above 70 years old do not seem to benefit from resection. The pros and cons of a resection should therefore be individually evaluated with the patient.
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Affiliation(s)
- D Wiese
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Baldingerstraße, 35043, Marburg, Deutschland.
| | - D K Bartsch
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Baldingerstraße, 35043, Marburg, Deutschland
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22
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Rossi RE, Elvevi A, Gallo C, Palermo A, Invernizzi P, Massironi S. Endoscopic techniques for diagnosis and treatment of gastro-entero-pancreatic neuroendocrine neoplasms: Where we are. World J Gastroenterol 2022; 28:3258-3273. [PMID: 36051341 PMCID: PMC9331536 DOI: 10.3748/wjg.v28.i26.3258] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/04/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs).
AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs.
METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published in the last 15 years, using both medical subject heading (MeSH) terms and free-language keywords: gastro-entero-pancreatic neuroendocrine neoplasms; endoscopy; ultrasound endoscopy; capsule endoscopy; double-balloon enteroscopy; diagnosis; therapy; staging.
RESULTS In the diagnostic setting, endoscopic ultrasonography (EUS) represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric, duodenal and rectal NENs. The diagnosis of small bowel NENs (sbNENs) has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy, which allow for direct visualization of the entire small bowel; however, data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive. From a therapeutic point of view, endoscopic removal is the treatment of choice for the majority of gastric NENs (type 1/2), for well-differentiated localized nonmetastatic duodenal NENs < 1 cm, confined to the submucosa layer and for < 10 mm, stage T1–T2, rectal NENs. EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients.
CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs. Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.
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Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Camilla Gallo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Andrea Palermo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
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23
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The Increasing Incidence of Neuroendocrine Neoplasms Worldwide: Current Knowledge and Open Issues. J Clin Med 2022; 11:jcm11133794. [PMID: 35807078 PMCID: PMC9267138 DOI: 10.3390/jcm11133794] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 06/28/2022] [Indexed: 02/01/2023] Open
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Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis. Pancreatology 2022; 22:644-650. [PMID: 35589512 DOI: 10.1016/j.pan.2022.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 04/20/2022] [Accepted: 04/26/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Current guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. METHODS We conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. RESULTS In our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% CONCLUSION: Using a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.
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25
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Bösch F, Ghadimi M, Angele MK. Personalisierte Resektionsverfahren bei neuroendokrinen Neoplasien des Pankreas. Zentralbl Chir 2022; 147:264-269. [DOI: 10.1055/a-1823-1275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungNeuroendokrine Neoplasien des Pankreas (pNEN) haben eine steigende Inzidenz und erhalten klinisch dadurch eine immer höhere Relevanz. Neben den hormonell inaktiven pNEN gibt es die
hormonproduzierenden Tumoren, und sowohl die inaktiven als auch die aktiven pNEN können entweder sporadisch oder hereditär vorkommen. Die Behandlung orientiert sich an tumorassoziierten
Faktoren, aber auch an individuellen patienteneigenen Gegebenheiten. Für die Behandlung sind individuelle maßgeschneiderte Konzepte notwendig, welche die jeweiligen Faktoren und
Gegebenheiten berücksichtigen.
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Affiliation(s)
- Florian Bösch
- Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen, Gottingen, Deutschland
| | - Michael Ghadimi
- Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen, Gottingen, Deutschland
| | - Martin K. Angele
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, München, Deutschland
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26
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [PMID: 35317548 PMCID: PMC8908345 DOI: 10.4240/wjgs.v14.i2.78] [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: 03/20/2021] [Revised: 10/18/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.
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Affiliation(s)
- Elettra Merola
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Andrea Michielan
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Umberto Rozzanigo
- Department of Radiology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Marco Erini
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Sandro Sferrazza
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Stefano Marcucci
- Department of Surgery, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Sartori
- Department of Pathology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Giovanni de Pretis
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Franca Chierichetti
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
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27
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How to Select Patients Affected by Neuroendocrine Neoplasms for Surgery. Curr Oncol Rep 2022; 24:227-239. [PMID: 35076884 DOI: 10.1007/s11912-022-01200-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2021] [Indexed: 11/03/2022]
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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: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [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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Cienfuegos JA, Hurtado-Pardo L, Rotellar F. Small pancreatic neuroendocrine tumours: observe and monitor or prompt surgical resection. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 114:1-4. [PMID: 34794318 DOI: 10.17235/reed.2021.8419/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Over recent decades there has been a significant increase in the annual incidence of neuroendocrine tumors of the pancreas (PanNets), from 0.4 to 0.8 per 100,000 inhabitants, due to the more widespread use of more sensitive imaging techniques (cross-sectional and functional imaging).
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Hurtado-Pardo L, Breeze CE, Cienfuegos JA, Benito A, Valentí V, Martí-Cruchaga P, Zozaya G, Martínez Regueira F, Pardo F, Rotellar Sastre F. Comparison of phenotypes and outcomes following resection of incidental versus symptomatic pancreatic neuroendocrine tumors. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 114:317-322. [PMID: 34315216 DOI: 10.17235/reed.2021.8096/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background/Aim Fifty to 70 percent of pancreatic neuroendocrine tumors are diagnosed incidentally. The objective of this study is to compare the phenotype and oncological outcomes of incidental versus symptomatic pancreatic neuroendocrine tumors. Methods A retrospective study was conducted identifying all incidental and symptomatic tumors resected between 2000 and 2019. Baseline characteristics, symptoms, operative variables and pathological stage were all recorded. In both groups, patterns of recurrence and overall and disease-free survival were analyzed. Results Fifty-one incidental and 45 symptomatic pancreatic tumor resections were performed. Symptomatic tumors were more frequent in women (29 vs 17; p=0.005), in younger patients (median years; 50 vs 58; p=0.012) and were detected at a more advanced stage (p=0.027). There were no differences in location and most resections (n= 49; 51%) were performed laparoscopically. There were no operative mortalities and 17 (17.7%) severe complications (≥IIIb on the Clavien-Dindo classification) were recorded with no differences between the two groups. With a median follow-up of 64.4 months (range 13.5 - 90), overall survival at 5 and 10 years was 89.7% and 72.8% for the non-incidental tumors, and 80.9% and 54.6% for the incidental tumors (p=ns). Disease-free survival in both groups (excluding M1a) was 71.2% and 47.5%, and 93.7% and 78.1%, respectively (p= ns). Conclusions Symptomatic tumors are more frequent in women and present at higher pathological stages. There were no significant differences in overall and disease-free survival between the two groups. Resection of incidental tumors ≥1.5 - 2 cm seems advisable, although each case should assessed on an individual basis.
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Affiliation(s)
| | - Charles E Breeze
- UCL Cancer Institute. University College London , United Kingdom
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Mowrey K, Northrup H, Rougeau P, Hashmi SS, Krueger DA, Ebrahimi-Fakhari D, Towbin AJ, Trout AT, Capal JK, Franz DN, Rodriguez-Buritica D. Frequency, Progression, and Current Management: Report of 16 New Cases of Nonfunctional Pancreatic Neuroendocrine Tumors in Tuberous Sclerosis Complex and Comparison With Previous Reports. Front Neurol 2021; 12:627672. [PMID: 33897589 PMCID: PMC8062856 DOI: 10.3389/fneur.2021.627672] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/15/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Tuberous sclerosis complex (TSC) is a genetic condition that causes benign tumors to grow in multiple organ systems. Nonfunctional pancreatic neuroendocrine tumors (PNETs) are a rare clinical feature of TSC with no specific guidelines outlined for clinical management at this time. Our purpose is to calculate the frequency of nonfunctional PNETs as well as characterize the presentation, current clinical management, and assess the impact of systemic mammalian target of rapamycin (mTOR) on nonfunctional PNETs in TSC. Methods: This retrospective chart review was performed by a query of the TS Alliance's Natural History Database and the Cincinnati Children's Hospital TSC Database for patients with nonfunctional PNET. Clinical data from these two groups was summarized for patients identified to have a nonfunctional PNET and compared to previously reported cases with TSC and nonfunctional PNETs. Results: Our calculated frequency of nonfunctional PNETs is 0.65%. We identified 16 individuals, nine males and seven females, with a median age of 18.0 years (interquartile range: −15.5 to 25.5). Just over half (56.3%, n = 9) of the patients provided results from genetic testing. Six had pathogenic variants in TSC2 whereas three had pathogenic variants in TSC1. The average age at PNET diagnosis was 15.0 years (range: 3–46 years). Almost all individuals were diagnosed with a PNET during routine TSC surveillance, 56.3% (n = 9) by MRI, 12.5% (n = 2) by CT, 25% (n = 4) by ultrasound, and 6.2% (n = 1) through a surgical procedure. Follow up after diagnosis involved 68.8% (n = 11) having serial imaging and nine of the sixteen individuals proceeding with surgical removal of the PNET. Eight individuals had a history of using systemic mTOR inhibitors. Tumor growth rate was slightly less in individuals taking an mTOR inhibitor (−0.8 mm/yr, IQR: −2.3 to 2.2) than those without (1.6 mm/yr; IQR: −0.99 to 5.01, p > 0.05). Conclusions: Nonfunctional PNETs occurred at younger ages in our TSC cohort and more commonly compared to ages and prevalence reported for the general population. PNETs in patients on systemic mTOR inhibitors had lower rates of growth. The outcome of this study provides preliminary evidence supporting the use of mTOR inhibitor therapy in conjunction with serial imaging as medical management for nonfunctional PNETs as an alternative option to invasive surgical removal.
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Affiliation(s)
- Kate Mowrey
- Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Hope Northrup
- Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Peyton Rougeau
- Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - S Shahrukh Hashmi
- Department of Pediatrics, Pediatric Research Center, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Darcy A Krueger
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Division of Neurology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Daniel Ebrahimi-Fakhari
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Andrew T Trout
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Jamie K Capal
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Division of Neurology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - David Neal Franz
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Division of Neurology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - David Rodriguez-Buritica
- Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
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