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Tacelli M, Gentiluomo M, Biamonte P, Castano JP, Berković MC, Cives M, Kapitanović S, Marinoni I, Marinovic S, Nikas I, Nosáková L, Pedraza-Arevalo S, Pellè E, Perren A, Strosberg J, Campa D, Capurso G. Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis. Semin Cancer Biol 2025; 112:112-125. [PMID: 40158764 DOI: 10.1016/j.semcancer.2025.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/07/2025] [Accepted: 03/19/2025] [Indexed: 04/02/2025]
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous tumors arising from neuroendocrine cells, representing approximately 10 % of all Gastro-Entero-Pancreatic neuroendocrine neoplasms. While most pNENs are sporadic, a subset is associated with genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1) or von Hippel-Lindau disease (VHL). pNENs are further classified into functioning and non-functioning tumors, with distinct clinical behaviors, prognoses, and treatment approaches. This review explores genetic and environmental biomarkers that influence the risk, prognosis, and therapeutic responses in pNENs. The epidemiology of pNENs reveals an increasing incidence, primarily due to advancements in imaging techniques. Genetic factors play a pivotal role, with germline mutations in MEN1, VHL, and other genes contributing to familial pNENs. Somatic mutations, including alterations in the mTOR pathway and DNA maintenance genes such as DAXX and ATRX, are critical in sporadic pNENs. These mutations, along with epigenetic dysregulation and transcriptomic alterations, underpin the diverse clinical and molecular phenotypes of pNENs. Emerging evidence suggests that epigenetic changes, including DNA methylation profiles, can stratify pNEN subtypes and predict disease progression. Environmental and lifestyle factors, such as diabetes, smoking, and chronic pancreatitis, have been linked to an increased risk of sporadic pNENs. While the association between these factors and tumor progression is still under investigation, their potential role in influencing therapeutic outcomes warrants further study. Advances in systemic therapies, including somatostatin analogs, mTOR inhibitors, and tyrosine kinase inhibitors, have improved disease management. Biomarkers such as Ki-67, somatostatin receptor expression, and O6-methylguanine-DNA methyltransferase (MGMT) status are being evaluated for their predictive value. Novel approaches, including the use of circulating biomarkers (NETest, circulating tumor cells, and ctDNA) and polygenic risk scores, offer promising avenues for non-invasive diagnosis and monitoring. Despite these advancements, challenges remain, including the need for large, well-annotated datasets and validated biomarkers. Future research should integrate multi-omics approaches and leverage liquid biopsy technologies to refine diagnostic, prognostic, and therapeutic strategies. Interdisciplinary collaborations and global consortia are crucial for overcoming current limitations and translating research findings into clinical practice. These insights hold promise for improving prevention, early detection, and tailored treatments, ultimately enhancing patient outcomes.
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Affiliation(s)
- Matteo Tacelli
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Paolo Biamonte
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Justo P Castano
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
| | - Maja Cigrovski Berković
- Department for Sport and Exercise Medicine, Faculty of Kinesiology University of Zagreb, Zagreb 10000, Croatia
| | - Mauro Cives
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Sanja Kapitanović
- Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb 10000, Croatia
| | - Ilaria Marinoni
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Sonja Marinovic
- Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb 10000, Croatia
| | - Ilias Nikas
- Medical School, University of Cyprus, Nicosia, Cyprus
| | - Lenka Nosáková
- Clinic of Internal Medicine - Gastroenterology, JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Bratislava, Slovakia
| | - Sergio Pedraza-Arevalo
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
| | - Eleonora Pellè
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Aurel Perren
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Jonathan Strosberg
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy.
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Figueira ERR, Montagnini AL, Okubo J, Fernandes AGV, Pereira MA, Ribeiro U, Herman P, Jukemura J. NON-FUNCTIONING SPORADIC PANCREATIC NEUROENDOCRINE TUMOR IS AN INDEPENDENT RISK FACTOR FOR RECURRENCE AFTER SURGICAL TREATMENT. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2025; 37:e1857. [PMID: 39841762 PMCID: PMC11745474 DOI: 10.1590/0102-6720202400063e1857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PNETs) are uncommon and heterogeneous neoplasms, often exhibiting indolent biological behavior. Their incidence is rising, largely due to the widespread use of high-resolution imaging techniques, particularly influencing the diagnosis of sporadic non-functioning tumors, which account for up to 80% of cases. While surgical resection remains the only curative option, the impact of factors such as tumor grade, size, and type on prognosis and recurrence is still unclear. AIMS To investigate prognostic risk factors and outcomes in patients with sporadic PNETs treated surgically. METHODS A retrospective analysis was conducted on patients with sporadic PNETs who underwent pancreatic resection. Data were collected from medical records. RESULTS A total of 113 patients were included: 32 with non-functioning tumors (NF-PNETs), 70 with insulinomas, and 11 with other functioning tumors (OF-PNETs). Patients with insulinoma were significantly younger, had a higher BMI, lower prevalence of comorbidities and ASA scores, and underwent significantly more pancreatic enucleations compared to patients with OF-PNET and NF-PNET. The insulinoma group had more grade I tumors, smaller tumor diameter, lower TNM staging, and lower disease recurrence rates. In univariate analysis, age, tumor type, tumor size, and TNM staging were identified as potential risk factors for tumor recurrence. In multivariate analysis, only the NF-PNET type was identified as an independent prognostic factor for disease recurrence. CONCLUSIONS NF-PNETs are an independent prognostic risk factor for disease recurrence. This finding supports the need for closer follow-up of patients with small tumors who are selected for conservative management.
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Affiliation(s)
| | | | - Jessica Okubo
- Universidade de São Paulo, Faculty of Medicine – São Paulo (SP), Brazil
| | | | | | - Ulysses Ribeiro
- Universidade de São Paulo, Faculty of Medicine – São Paulo (SP), Brazil
| | - Paulo Herman
- Universidade de São Paulo, Faculty of Medicine – São Paulo (SP), Brazil
| | - José Jukemura
- Universidade de São Paulo, Faculty of Medicine – São Paulo (SP), Brazil
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Kim J, Hong SS, Kim SH, Hwang HK, Kang CM. Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study. World J Surg Oncol 2024; 22:115. [PMID: 38671431 PMCID: PMC11046948 DOI: 10.1186/s12957-024-03383-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 04/06/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PNETs) represent 1-2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. METHODS This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. RESULTS Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence. CONCLUSION This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.
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Affiliation(s)
- Juwan Kim
- Department of surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Soo Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Sung Hyun Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Ho Kyong Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, Yonsei University College of Medicine, Seoul, Korea.
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea.
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Kartik A, Armstrong VL, Stucky CC, Wasif N, Fong ZV. Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:1501. [PMID: 38672582 PMCID: PMC11048062 DOI: 10.3390/cancers16081501] [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: 02/20/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.
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Affiliation(s)
| | | | | | | | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ 85054, USA
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Heo S, Park HJ, Kim HJ, Kim JH, Park SY, Kim KW, Kim SY, Choi SH, Byun JH, Kim SC, Hwang HS, Hong SM. Prognostic value of CT-based radiomics in grade 1-2 pancreatic neuroendocrine tumors. Cancer Imaging 2024; 24:28. [PMID: 38395973 PMCID: PMC10885493 DOI: 10.1186/s40644-024-00673-z] [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: 08/03/2023] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Surgically resected grade 1-2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. METHODS This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1-2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models' performance for predicting RFS and overall survival (OS) was evaluated using Harrell's C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p < 0.001) and discrimination (IDI, 0.071, p < 0.001) for prediction of 3-year RFS. CONCLUSIONS Our CR-model outperformed the current clinical staging system in prediction of the prognosis for G1-2 PanNETs and added incremental value for predicting postoperative recurrence. The CR-model enables precise identification of high-risk patients, guiding personalized treatment planning to improve outcomes in surgically resected grade 1-2 PanNETs.
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Affiliation(s)
- Subin Heo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea
| | - Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea.
| | - Jung Hoon Kim
- Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea
| | - Seo Young Park
- Department of Statistics and Data Science, Korea National Open University, Seoul, Republic of Korea
| | - Kyung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hee Sang Hwang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Park YJ, Park YS, Kim ST, Hyun SH. A Machine Learning Approach Using [ 18F]FDG PET-Based Radiomics for Prediction of Tumor Grade and Prognosis in Pancreatic Neuroendocrine Tumor. Mol Imaging Biol 2023; 25:897-910. [PMID: 37395887 DOI: 10.1007/s11307-023-01832-7] [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: 01/11/2023] [Revised: 05/30/2023] [Accepted: 06/19/2023] [Indexed: 07/04/2023]
Abstract
PURPOSE We sought to develop and validate machine learning (ML) models for predicting tumor grade and prognosis using 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET)-based radiomics and clinical features in patients with pancreatic neuroendocrine tumors (PNETs). PROCEDURES A total of 58 patients with PNETs who underwent pretherapeutic [18F]FDG PET/computed tomography (CT) were retrospectively enrolled. PET-based radiomics extracted from segmented tumor and clinical features were selected to develop prediction models by the least absolute shrinkage and selection operator feature selection method. The predictive performances of ML models using neural network (NN) and random forest algorithms were compared by the areas under the receiver operating characteristic curves (AUROCs) and validated by stratified five-fold cross validation. RESULTS We developed two separate ML models for predicting high-grade tumors (Grade 3) and tumors with poor prognosis (disease progression within two years). The integrated models consisting of clinical and radiomic features with NN algorithm showed the best performances than the other models (stand-alone clinical or radiomics models). The performance metrics of the integrated model by NN algorithm were AUROC of 0.864 in the tumor grade prediction model and AUROC of 0.830 in the prognosis prediction model. In addition, AUROC of the integrated clinico-radiomics model with NN was significantly higher than that of tumor maximum standardized uptake model in predicting prognosis (P < 0.001). CONCLUSIONS Integration of clinical features and [18F]FDG PET-based radiomics using ML algorithms improved the prediction of high-grade PNET and poor prognosis in a non-invasive manner.
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Affiliation(s)
- Yong-Jin Park
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
- Department of Nuclear Medicine, Ajou University Medical Center, Ajou University School of Medicine, 164, Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea
| | - Young Suk Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea
| | - Seung Tae Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea
| | - Seung Hyup Hyun
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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Sun C, Xu H, Wang S, Li K, Qin P, Liang B, Xu L. Lifestyle, clinical and histological indices-based prediction models for survival in cancer patients: a city-wide prospective cohort study in China. J Cancer Res Clin Oncol 2023; 149:9965-9978. [PMID: 37256382 DOI: 10.1007/s00432-023-04888-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/19/2023] [Indexed: 06/01/2023]
Abstract
PURPOSE We developed a nomogram to predict 3-year, 5-year and 7-year cancer survival rates of cancer patients. METHODS This prospective cohort study included 20,491 surviving patients first diagnosed with cancer in Guangzhou from 2010 to 2019. They were divided into a training and a validation group. Lifestyle, clinical and histological parameters (LCH) were included in multivariable Cox regression. Akaike information criterion was used to select prediction factors for the nomogram. The discrimination and calibration of models were assessed by concordance index (C-index), area under time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. We used net reclassification index (NRI) and integrated discrimination improvement (IDI) to compare the clinical utility of LCH prediction model with the prediction model based on lifestyle factors (LF). RESULTS 13 prediction factors including age, sex, BMI, smoking status, physical activity, sleep duration, regular diet, tumor grading, TNM stage, multiple primary cancer and anatomical site were included in the LCH model. The LCH model showed satisfactory discrimination and calibration (C-index = 0.81 (95% CI 0.80-0.82) for training group and 0.80 (0.79-0.81) for validation group, both time-dependent AUC > 0.70). The LF model including smoking status, physical activity, sleep duration, regular diet, and BMI showed less satisfactory discrimination (C-index = 0.60 (95% CI 0.59-0.61) for training and 0.60 (0.58-0.62) for validation group). The LCH model had better accuracy and discriminative ability than the LF model, as indicated by positive NRI and IDI values. CONCLUSIONS The LCH model shows good accuracy, clinical utility and precise prognosis prediction, and may serve as a tool to predict cancer survival of cancer patients.
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Affiliation(s)
- Ce Sun
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Huan Xu
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China
| | - Suixiang Wang
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China
| | - Ke Li
- The Operation Management Department, Guangzhou Center for Disease Control and Prevention, Guangzhou, 510403, China
| | - Pengzhe Qin
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China
| | - Boheng Liang
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China.
| | - Lin Xu
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
- School of Public Health, University of Hong Kong, Hong Kong, China.
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Weich A, Serfling SE, Schlötelburg W, Higuchi T, Hartrampf PE, Schirbel A, Heinrich M, Buck AK, Rowe SP, Kosmala A, Werner RA. Impact of CXCR4-Directed PET/CT on Staging and Proposed Oncologic Management in Patients With Digestive System Tumors. Clin Nucl Med 2023; 48:586-593. [PMID: 37167408 DOI: 10.1097/rlu.0000000000004674] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
PURPOSE To elucidate the influence of CXC motif chemokine receptor 4 (CXCR4)-directed imaging on staging and proposed oncologic management in patients with digestive system tumors compared with guideline-appropriate imaging (GAI). METHODS From our PET/CT database, we retrospectively identified 37 patients with advanced digestive system tumors, which had been scheduled for CXCR4-targeted [ 68 Ga]Ga-pentixafor PET/CT for potential theranostic considerations. In all subjects, concurrent GAI was also available. Patients were afflicted with gastroenteropancreatic neuroendocrine neoplasms (21/37 [56.8%]), pancreatic duct adenocarcinoma (6/37 [16.2%]), cholangiocarcinoma (5/37 [13.5%]), hepatocellular carcinoma (4/37 [10.8%]), and colorectal carcinoma (1/37 [2.7%]). Staging results and impact on proposed oncologic management by a board-certified gastroenterologist were compared between GAI and [ 68 Ga]Ga-pentixafor PET/CT. RESULTS Relative to GAI, CXCR4-directed PET/CT resulted in staging changes in 14 of 37 patients (37.8%). Upstaging was seen in 1 of 14 patients (7.1%), whereas downstaging was recorded in the remaining 13 of 14 patients (92.9%). Among those, staging changes would not have triggered any changes in oncological management in 4 of 14 (28.6%). For the remaining 10 of 14 patients (71.4%), however, findings on [ 68 Ga]Ga-pentixafor PET/CT would have impacted subsequent clinical algorithm, including the necessity for further diagnostic steps or failure to initiate antitumor therapy. CONCLUSION [ 68 Ga]Ga-pentixafor PET/CT missed tumor lesions in 13 patients with digestive system tumors, which would have led to inappropriate downstaging and clinical treatment of 10 patients. As such, our results do not support a more widespread use of [ 68 Ga]Ga-pentixafor PET/CT for clinical staging in those tumor entities.
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Affiliation(s)
| | | | - Wiebke Schlötelburg
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | | | - Philipp E Hartrampf
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Andreas Schirbel
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | | | - Andreas K Buck
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Steven P Rowe
- Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Sciences, Baltimore, MD
| | - Aleksander Kosmala
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
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Li M, Wu L, Luo S, Liu Y, Sun C, Li E, Wang J, Li B, Huang Z, Ge J, Lei J, Zhou F, Liao W. Validation of a supplementary condition of eighth AJCC staging system for stage II hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1217-1225. [PMID: 36690533 DOI: 10.1016/j.ejso.2023.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/09/2023] [Accepted: 01/16/2023] [Indexed: 01/19/2023]
Abstract
INTRODUCTION The eighth American Joint Committee on Cancer (AJCC) staging system was flawed regarding the prognosis of stage II hepatocellular carcinoma (HCC). The aims of this study were to reveal the defect and make updates. METHODS Clinical and survival data of HCC patients from the Surveillance, Epidemiology, and End Results database were used. We re-classified stage II into T2aN0M0 (tumors >2 cm with vascular invasion) and T2bN0M0 (multiple tumors ≤5 cm). The Kaplan-Meier method and log-rank test were used to estimate differences in overall survival (OS). Three propensity score matching analyses without (PSM1) or with (PSM2 and PSM3) consideration of surgical treatment were performed. Cox regression was used to reveal risk factors. RESULTS HCC patients identified as T1bN0M0, T2aN0M0, T2bN0M0, and T3N0M0 were recruited. OS in T2N0M0 was consistent with the eighth AJCC staging system after PSM1. T2bN0M0 had increased OS compared with T2aN0M0 after PSM2 (hazard ratio [HR] = 1.36; 95% confidence interval [CI] = 1.06-1.73; P = 0.0141) or PSM3 (HR = 1.18; 95%CI = 1.01-1.37; P = 0.0283). No survival benefit existed between T1bN0M0 and T2bN0M0 after PSM2 (HR = 0.92; 95%CI = 0.80-1.05; P = 0.2171) or PSM3 (HR = 0.92; 95%CI = 0.84-1.01; P = 0.0888). Compared with T2aN0M0, T3N0M0 had shorter OS after PSM2 (HR = 0.64; 95%CI = 0.50-0.82; P = 0.0003) or PSM3 (HR = 0.63; 95%CI = 0.54-0.73; P < 0.0001). Cox regression analysis revealed that surgical treatment was associated with better prognosis (HR = 0.3; 95%CI = 0.3-0.4; P < 0.001). CONCLUSIONS The current staging for T2N0M0 is imprecise because surgical treatment is not adequately evaluated and would be ineffective if the proportion of T2bN0M0 patients with surgical treatment was increased.
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Affiliation(s)
- Min Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Linquan Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Shuaiwu Luo
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Yaran Liu
- Department of Pharmacy, Nanchang University, No.999, University Avenue, Nanchang, 330006, China
| | - Chi Sun
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Enliang Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Jiakun Wang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Bowen Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Zhihao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Jin Ge
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Jun Lei
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Fan Zhou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Wenjun Liao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China.
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10
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Shi XY, Wang Y, Zhou X, Xie ML, Ma Q, Wang GX, Zhan J, Shao YM, Wei B. A population-based nomogram to individualize treatment modality for pancreatic cancer patients underlying surgery. Sci Rep 2023; 13:4856. [PMID: 36964145 PMCID: PMC10038997 DOI: 10.1038/s41598-023-31292-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 03/09/2023] [Indexed: 03/26/2023] Open
Abstract
As the most aggressive tumor, TNM staging does not accurately identify patients with pancreatic cancer who are sensitive to therapy. This study aimed to identify associated risk factors and develop a nomogram to predict survival in pancreatic cancer surgery patients and to select the most appropriate comprehensive treatment regimen. First, the survival difference between radiotherapy and no radiotherapy was calculated based on propensity score matching (PSM). Cox regression was conducted to select the predictors of overall survival (OS). The model was constructed using seven variables: histologic type, grade, T stage, N stage, stage, chemotherapy and radiotherapy. All patients were classified into high- or low-risk groups based on the nomogram. The nomogram model for OS was established and showed good calibration and acceptable discrimination (C-index 0.721). Receiver operating characteristic curve (ROC) and DCA curves showed that nomograms had better predictive performance than TNM stage. Patients were divided into low-risk and high-risk groups according to nomogram scores. Radiotherapy is recommended for high-risk patients but not for low-risk patients. We have established a well-performing nomogram to effectively predict the prognosis of pancreatic cancer patients underlying surgery. The web version of the nomogram https://rockeric.shinyapps.io/DynNomapp/ may contribute to treatment optimization in clinical practice.
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Affiliation(s)
- Xiao-Ya Shi
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China
| | - Yan Wang
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China
| | - Xuan Zhou
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China
| | - Meng-Li Xie
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China
| | - Qian Ma
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China
| | - Gan-Xin Wang
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China
| | - Jing Zhan
- Department of Oncology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yi-Ming Shao
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong Province, China
| | - Bai Wei
- Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang District, Wuhan, 430077, Hubei Province, China.
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11
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Venous invasion and lymphatic invasion are correlated with the postoperative prognosis of pancreatic neuroendocrine neoplasm. Surgery 2023; 173:365-372. [PMID: 36123176 DOI: 10.1016/j.surg.2022.08.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/25/2022] [Accepted: 08/04/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND To determine treatment strategies corresponding to a wide range of pancreatic neuroendocrine neoplasms staging, easier-to-use and detailed prognostic classification is required. METHODS Patients with pancreatic neuroendocrine neoplasms who underwent curative-intent surgery at the University of Tokyo Hospital between 2000 and 2018 were retrospectively reviewed. The presence or absence of venous and lymphatic invasion was assessed. Multivariable analysis was performed to identify the risk factors of shorter overall survival and recurrence-free survival. Patients were classified into the following 3 groups: a lymphovascular invasion 0 group, whereby both venous and lymphatic invasion were negative; an lymphovascular invasion 1 group, where either of the 2 was positive; and an lymphovascular invasion 2 group, where both were positive. The survival curves and recurrence patterns of the 3 groups were compared. RESULTS Eighty-nine patients were analyzed. Multivariable analysis revealed that lymphatic invasion and Ki-67 index (≥ 3.0%) were independent prognostic factors of recurrence-free survival (hazard ratio: 5.2 and 3.6). Fifty-three patients were classified as lymphovascular invasion 0, 26 as lymphovascular invasion 1, and 10 as lymphovascular invasion 2. The recurrence-free survival curves of the 3 groups were significantly stratified (10-year recurrence-free survival: 89.1% in lymphovascular invasion 0, 57.1% in lymphovascular invasion 1, and 18.3% in lymphovascular invasion 2). Five-year cumulative liver and lymph node metastasis of lymphovascular invasion 0, lymphovascular invasion 1, and lymphovascular invasion 2 were well stratified at 0% and 3.8%, 15.8% and 23.1%, and 33.3% and 70.0%, respectively. CONCLUSION Postoperative prognosis of resected pancreatic neuroendocrine neoplasms could be finely classified by venous invasion and lymphatic invasion. Management after curative-intent surgery for pancreatic neuroendocrine neoplasms may be changed by this new classification.
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12
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Kosmala A, Serfling SE, Schlötelburg W, Lindner T, Michalski K, Schirbel A, Higuchi T, Hartrampf PE, Buck AK, Weich A, Werner RA. Impact of 68 Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors. Clin Nucl Med 2023; 48:35-42. [PMID: 36354691 PMCID: PMC9762711 DOI: 10.1097/rlu.0000000000004480] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/30/2022] [Indexed: 11/12/2022]
Abstract
PURPOSE We aimed to determine the impact of fibroblast activation protein inhibitor (FAPI)-directed molecular imaging on staging and therapeutic management in patients affected with digestive system tumors when compared with guideline-compatible imaging (GCI). PATIENTS AND METHODS Thirty-two patients with tumors of the digestive system were included: colon adenocarcinoma, 2/32 (6.3%); hepatocellular carcinoma (HCC), 6/32 (18.8%); pancreatic duct adenocarcinoma (PDAC), 6/32 (18.8%), and gastroenteropancreatic neuroendocrine neoplasms, 18/32 (56.3%). All patients underwent GCI and 68 Ga-FAPI-04 PET/CT within median 4 days. Staging outcomes and subsequent treatment decisions were compared between GCI and 68 Ga-FAPI-04 PET/CT. RESULTS Compared with GCI, 68 Ga-FAPI-04 PET/CT led to staging changes in 15/32 patients (46.9%). Among those, downstaging was recorded in 3/15 cases (20.0%) and upstaging in the remaining 12/15 patients (HCC, 4/12 [33.3%]; PDAC, 4/12 [33.3%]; neuroendocrine neoplasms, 3/12 [25%]; colon adenocarcinoma, 1/12 [8.3%]). Therapeutic management was impacted in 8/32 patients (25.0%), including 4 instances of major and 4 instances of minor therapeutic changes. The highest proportion of treatment modifications was observed in patients diagnosed with PDAC and HCC in 6/8 (75%). CONCLUSIONS In patients affected with digestive system tumors, 68 Ga-FAPI-04 PET/CT resulted in staging changes in more than 46% and therapeutic modifications in 25% of the cases, in particular in patients with HCC and PDAC. In clinical routine, such findings may favor a more widespread adoption of FAP-directed imaging in those tumor types.
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Affiliation(s)
- Aleksander Kosmala
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Sebastian E. Serfling
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Wiebke Schlötelburg
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Thomas Lindner
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Kerstin Michalski
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Andreas Schirbel
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Takahiro Higuchi
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
- Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Philipp E. Hartrampf
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Andreas K. Buck
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Alexander Weich
- Department of Internal Medicine II, Gastroenterology
- Würzburg NET Zentrum, European Neuroendocrine Tumor Society–Center of Excellence, University Hospital Würzburg, Würzburg, Germany
| | - Rudolf A. Werner
- From the Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
- Würzburg NET Zentrum, European Neuroendocrine Tumor Society–Center of Excellence, University Hospital Würzburg, Würzburg, Germany
- Johns Hopkins School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, Baltimore, MD
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13
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Lim S, Chong L, Peeroo S, Onasanya O, He E, Banting S, Croagh D. Recurrence and outcomes of non-functional pancreatic neuroendocrine tumours post-resection: an Australian retrospective, multicentre cohort study. ANZ J Surg 2023; 93:160-165. [PMID: 36562118 DOI: 10.1111/ans.18204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 11/30/2022] [Accepted: 12/01/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Pancreatic neuroendocrine tumours (PNETs) are heterogenous entities with variable clinical outlook. The prevalence of PNETs is increasing in Australia. Despite this, data on peri-operative management and post-operative prognosis for Australian patients is scant in the literature. METHODS Patients from two tertiary hospitals in Victoria were recruited. Inclusion criteria included patients who underwent curative surgical resection for primary, non-functioning, PNETs without metastases from January 2011 to December 2021. Patients were identified via histopathological reports, CMBS and ICD-10 codes. Data were sourced from Electronic Medical Records, outpatient notes and letters. RESULTS Sixty-three patients (34 Male, 29 Female) underwent surgical resection for PNETs. Fifty-three patients (84.1%) had a post-operative complication, and 21 (33.3%) had severe complications. Two patients had disease recurrence. Head PNETs had higher Ki-67% (5.33 vs. 2.72, P = 0.29), and likelihood of nodal spread (9 (36%) vs. 4 (16%), P = 0.054). Pancreatic Head resections were also associated with more frequent ICU admissions (21 (84%) vs. 18 (54.5), P = 0.024), longer ICU stays (4.05 vs. 2.17 days, P = 0.10) and hospital stays (26.76 vs. 8.27 days, P = <0.001). CONCLUSION Within the limitations of this study, it demonstrates that surgical resection of PNET carries a significant morbidity with a low rate of recurrence. Additionally, Pancreatic head NETs may be associated with higher grades and increased likelihood of nodal metastases. Considering this, careful patient selection is paramount.
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Affiliation(s)
- Sean Lim
- Department of General Surgery, Monash Health, Melbourne, Australia
| | - Lynn Chong
- Department of General Surgery, St Vincent's Health, Melbourne, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Australia
| | - Saania Peeroo
- Department of General Surgery, Monash Health, Melbourne, Australia
| | - Olukunle Onasanya
- Department of General Surgery, St Vincent's Health, Melbourne, Australia
| | - Evelyn He
- Department of General Surgery, St Vincent's Health, Melbourne, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Australia
| | - Simon Banting
- Department of General Surgery, St Vincent's Health, Melbourne, Australia
| | - Daniel Croagh
- Department of General Surgery, Monash Health, Melbourne, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Australia.,Department of Surgery, Monash University, Melbourne, Australia
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Chen J, Chen Q, Deng Y, Jiang Y, Huang Z, Zhou J, Zhao H, Cai J. Development and Validation of Prognostic Nomograms for Periampullary Neuroendocrine Neoplasms: A SEER Database Analysis. Curr Oncol 2022; 30:344-357. [PMID: 36661677 PMCID: PMC9858183 DOI: 10.3390/curroncol30010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/20/2022] [Accepted: 12/01/2022] [Indexed: 12/28/2022] Open
Abstract
(1) Background: Periampullary neuroendocrine neoplasms (NENs) are rare tumors that lack a prognostic prediction model. We aimed to design comprehensive and effective nomograms to predict prognosis; (2) Methods: Univariate and multivariate Cox analyses were used to screen out significant variables for the construction of the nomograms. The discrimination and calibration of the nomograms were carried out using calibration plots, concordance indices (C-indices), and area under time-dependent receiver operating characteristic curves (time-dependent AUCs). Decision curve analysis (DCA) was used to compare the clinical applicability of the nomograms, TNM (Tumor- Node-Metastasis) stage, and SEER stage; (3) Results: The independent risk factors for overall survival (OS) and cancer-specific survival (CSS) of patients with periampullary NENs included age, tumor size, histology, differentiation, N stage, M stage, and surgery, which were used to construct the nomograms. The calibration curves and C-indices showed a high degree of agreement between the predicted and actual observed survival rates. The AUCs displayed good calibration and acceptable discrimination of the nomograms. Additionally, the DCA curves indicated that the nomograms showed better clinical applicability; (4) Conclusions: We developed and validated nomogram prognostic models for patients with periampullary NENs. The nomograms provided insightful and applicable tools to evaluate prognosis.
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Affiliation(s)
- Jinghua Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qichen Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yiqiao Deng
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yujuan Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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15
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Comparison of oncologic outcomes between open and laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma using data from the KOTUS-BP national database: overcoming selection bias and the necessity of definite indications. HPB (Oxford) 2022; 24:1804-1812. [PMID: 35871134 DOI: 10.1016/j.hpb.2022.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 01/09/2022] [Accepted: 01/18/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database. METHODS A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP). RESULTS ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion. CONCLUSION LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.
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Surgical Outcomes, Long-Term Survivals and Staging Systems of World Health Organization G3 Pancreatic Neuroendocrine Tumors. J Clin Med 2022; 11:jcm11185253. [PMID: 36142900 PMCID: PMC9502090 DOI: 10.3390/jcm11185253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 08/30/2022] [Accepted: 08/31/2022] [Indexed: 11/17/2022] Open
Abstract
Background: In 2017, the World Health Organization (WHO) defined a new category of pancreatic neuroendocrine neoplasms named G3 pancreatic neuroendocrine tumors (p-NETs), whose surgical outcomes, long-term survivals and staging systems have not been well documented. Methods: Data from eligible patients with G3 p-NETs defined using the WHO 2017 grading classification at our institute were retrospectively analyzed. Results: Our study enrolled 80 patients with WHO G3 p-NETs, including 50 women and 30 men. The accumulative 5-year overall survival (OS) of G3 p-NETs was 29.7%. The current staging system by the American Joint Committee on Cancer (AJCC) failed to discriminate the survival difference between Stage II and Stage III (p = 0.172), while notable differences with regard to the OS were statistically offered between each stage using the modified tumor−node−metastasis (mTNM) staging system (all p < 0.05). The OS of patients receiving surgical resection was significantly better than those with palliative operation (p < 0.05). Both the current AJCC system and proposed mTNM system were independent predictors for the OS of G3 p-NETs (p = 0.017 and p = 0.032, respectively). The 95% confidence intervals of the proposed mTNM staging system were smaller than that of the current AJCC system (0.626−8.217 and 0.329−10.013, respectively), indicating a relatively more accurate predictive ability. Conclusion: Our demonstration revealed that surgical resection was an independent predictor for the favorable prognosis of patients with G3 p-NETs. Moreover, the new mTNM staging system was more suitable and practical than the current AJCC system for stratifying G3 p-NETs into prognostic groups.
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17
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Zhang XF, Xue F, Wu Z, Lopez-Aguiar AG, Poultsides G, Makris E, Rocha F, Kanji Z, Weber S, Fisher A, Fields R, Krasnick BA, Idrees K, Smith PM, Cho C, Beems M, Lyu Y, Maithel SK, Pawlik TM. Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors. Ann Surg 2022; 275:e773-e780. [PMID: 32511134 PMCID: PMC10188291 DOI: 10.1097/sla.0000000000004039] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system. BACKGROUND Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial. METHODS Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification. RESULTS The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts. CONCLUSION A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | | | | | - Flavio Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Zaheer Kanji
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Alexander Fisher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Ryan Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Bradley A Krasnick
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Paula M Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Cliff Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Yi Lyu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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Wang H, Ding D, Qin T, Zhang H, Liu J, Zhao J, Wu CH, Javed A, Wolfgang C, Guo S, Chen Q, Zhao W, Shi W, Zhu F, Guo X, Li X, Peng F, He R, Xu S, Jin J, Wu Y, Nuer A, Edil B, Tien YW, Jin G, Zheng L, He J, Liu J, Liu Y, Wang M, Qin R. Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors. HPB (Oxford) 2022; 24:681-690. [PMID: 34836754 DOI: 10.1016/j.hpb.2021.10.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/15/2021] [Accepted: 10/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.
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Affiliation(s)
- Hebin Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ding Ding
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Tingting Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Jun Liu
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong 250000, China
| | - Junfang Zhao
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Chien-Hui Wu
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei 10002, Taiwan
| | - Ammar Javed
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Christopher Wolfgang
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Shiwei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai 200433, China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
| | - Weihong Zhao
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Wei Shi
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong 250000, China
| | - Feng Zhu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xingjun Guo
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xu Li
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Feng Peng
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ruizhi He
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Simiao Xu
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jikuan Jin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Yi Wu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Abula Nuer
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Barish Edil
- Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei 10002, Taiwan
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai 200433, China
| | - Lei Zheng
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jin He
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jianhua Liu
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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Han IW, Park J, Park EY, Yoon SJ, Jin G, Hwang DW, Jiang K, Kwon W, Xu X, Heo JS, Fu DL, Lee WJ, Bai X, Yoon YS, Yang YM, Ahn KS, Yuan C, Lee HK, Sun B, Park EK, Lee SE, Kang S, Lou W, Park SJ. Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries. Cancers (Basel) 2022; 14:cancers14041038. [PMID: 35205787 PMCID: PMC8870171 DOI: 10.3390/cancers14041038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/10/2022] [Accepted: 02/16/2022] [Indexed: 11/23/2022] Open
Abstract
Simple Summary No consensus has been reached regarding whether nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) ≤ 2 cm should be resected or observed. In this retrospective international multicenter study, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from 2000 to 2017 were enrolled and their medical records were reviewed. Tumor size > 1.5 cm, Ki-67 index ≥ 3%, and nodal metastasis were independent adverse prognostic factors for survival after multivariable analysis. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs. Abstract Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16–80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80–10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29–8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48–12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01–27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.
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Affiliation(s)
- In Woong Han
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (I.W.H.); (S.J.Y.); (J.S.H.)
| | - Jangho Park
- Center for Liver and Pancreatobiliary Cancer, Research Institute and Hospital of National Cancer Center, Goyang 10408, Korea;
| | - Eun Young Park
- Biostatistics Collaboration Team, Research Institute and Hospital of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Korea;
| | - So Jeong Yoon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (I.W.H.); (S.J.Y.); (J.S.H.)
| | - Gang Jin
- Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Kuirong Jiang
- Department of General Surgery, Pancreas Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China;
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Xuefeng Xu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
| | - Jin Seok Heo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (I.W.H.); (S.J.Y.); (J.S.H.)
| | - De-Liang Fu
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China;
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul 03722, Korea;
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China;
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul 13620, Korea;
| | - Yin-Mo Yang
- Department of General Surgery, The First Hospital of Peking University, Beijing 100034, China;
| | - Keun Soo Ahn
- Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu 42601, Korea;
| | - Chunhui Yuan
- Department of General Surgery, The Third Hospital of Peking University, Beijing 100083, China;
| | - Hyeon Kook Lee
- Department of Surgery, Ewha Womans University College of Medicine, Seoul 07804, Korea;
| | - Bei Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
| | - Eun Kyu Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Chonnam National University Hospital, Gwangju 61469, Korea;
| | - Seung Eun Lee
- Department of Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul 06973, Korea;
| | - Sunghwa Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Dong-A University Hospital, Busan 49201, Korea;
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
- Correspondence: (W.L.); (S.-J.P.); Tel.: +86-136-8197-1683 (W.L.); +82-31-920-1640 (S.-J.P.)
| | - Sang-Jae Park
- Center for Liver and Pancreatobiliary Cancer, Research Institute and Hospital of National Cancer Center, Goyang 10408, Korea;
- Correspondence: (W.L.); (S.-J.P.); Tel.: +86-136-8197-1683 (W.L.); +82-31-920-1640 (S.-J.P.)
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Coelho S, Costa C, Santos AP, Souteiro P, Oliveira J, Oliveira J, Azevedo I, Torres I, Bento MJ. Pancreatic neuroendocrine neoplasms: survival trend analysis of a comprehensive center. ENDOCRINE ONCOLOGY (BRISTOL, ENGLAND) 2022; 2:32-41. [PMID: 37435456 PMCID: PMC10259287 DOI: 10.1530/eo-22-0043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 04/20/2022] [Indexed: 07/13/2023]
Abstract
Objectives Therapeutic options for pancreatic neuroendocrine neoplasia (Pan-NEN) have increased over the last decade. We aim to understand the evolution of the prognosis of patients with diagnosis of Pan-NEN within a 12-year period, considering the implementation of new treatments. Methods This study is a retrospective cohort study of patients diagnosed with Pan-NENs between 2006 and 2017. Survival outcome estimates were calculated by Kaplan-Meier method. The impact of baseline clinicopathological characteristics on survival was explored with the use of Cox proportional hazard model. Results Of the 97 patients, 77 (79.9%) had well-differentiated neuroendocrine tumor (NET) according to WHO 2010 classification, and 52 (53.6%) had localized or locoregional disease. There were no differences between clinicopathological characteristics and survival outcomes when comparing patients diagnosed between 2006-2011 and 2012-2017. Neuroendocrine carcinoma - HR 2.76, 95% CI 1.17-6.55 - and stages III and IV at diagnosis were independent poor prognostic factors - HR 6.02, 95% CI 2.22-16.33 and HR 6.93, 95% CI 2.94-16.32, respectively. Conclusions The new therapeutic approaches did not induce better survival outcomes on Pan-NEN in recent years. This is possibly due to the indolent nature of NET grades 1 and 2, even metastatic, allowing patients to be submitted to new target therapies along their disease course.
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Affiliation(s)
- Sara Coelho
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Cláudia Costa
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Ana Paula Santos
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
- Research Center, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Pedro Souteiro
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Joana Oliveira
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Júlio Oliveira
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Isabel Azevedo
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Isabel Torres
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Maria José Bento
- Department of Epidemiology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
- School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
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21
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Keihanian T, Othman M. Epidemiology, Pathogenesis, and Prognosis of Pancreatic Neuroendocrine Tumors. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:623-637. [DOI: 10.1007/978-3-030-41683-6_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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Ma H, Kan Y, Yang JG. Clinical value of 68Ga-DOTA-SSTR PET/CT in the diagnosis and detection of neuroendocrine tumors of unknown primary origin: a systematic review and meta-analysis. Acta Radiol 2021; 62:1217-1228. [PMID: 32985224 DOI: 10.1177/0284185120958412] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND The ability of 68Ga-DOTA-SSTR to detect the primary sites of neuroendocrine tumors (NETs) remains undetermined, and the clinical benefit of this imaging agent is not clear. PURPOSE To evaluate the diagnostic accuracy of 68Ga-DOTA-SSTR for carcinoma unknown primary (CUP) neuroendocrine tumors and to further analyze the detection rate of 68Ga-DOTA-SSTR for primary and metastatic sites. MATERIAL AND METHODS A comprehensive literature search of PubMed/MEDLINE and ScienceDirect was performed in October 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS A total of 10 studies (484 patients, mean age = 56.6 ± 4.3 years) were included in the study. The pooled sensitivity and specificity of 68Ga-DOTA-SSTR in identifying CUP-NETs were 82% and 55%, respectively. The area under the receiver operating characteristic curve was 69%. Regarding metastasis sites, 68Ga-DOTA-SSTR found the most metastases in the liver (57.9%), followed by the lymph nodes (22.8%), bones (12.8%), lung (2.8%), and others (1.7%). The pooled detection rate of 68Ga-DOTA-SSTR for CUP-NETs was 61%. CONCLUSION The present study demonstrated the high diagnostic sensitivity of 68Ga-DOTA-SSTR for CUP-NETs. 68Ga-DOTA-SSTR PET/CT was highly effective in locating the primary and metastatic sites of CUP-NETs.
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Affiliation(s)
- Huan Ma
- Nuclear Medicine Department, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Ying Kan
- Nuclear Medicine Department, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Ji-gang Yang
- Nuclear Medicine Department, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
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23
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Ruff SM, Standring O, Wu G, Levy A, Anantha S, Newman E, Karpeh MS, Nealon W, Deutsch GB, Weiss MJ, DePeralta DK. Ampullary Neuroendocrine Tumors: Insight into a Rare Histology. Ann Surg Oncol 2021; 28:8318-8328. [PMID: 34312800 DOI: 10.1245/s10434-021-10371-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/11/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.
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Affiliation(s)
- Samantha M Ruff
- Department of General Surgery, Northwell Health, Queens, NY, USA
| | - Oliver Standring
- Department of General Surgery, Northwell Health, Queens, NY, USA
| | - Grace Wu
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Anna Levy
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Monter Cancer Center, North New Hyde Park, NY, USA
| | - Sandeep Anantha
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Monter Cancer Center, North New Hyde Park, NY, USA
| | - Elliot Newman
- Lenox Hill Hospital Surgical Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health Cancer Institute, New York, NY, USA
| | - Martin S Karpeh
- Department of Surgical Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Huntington Hospital, Huntington, NY, USA
| | - William Nealon
- Department of General Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Queens, NY, USA
| | - Gary B Deutsch
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Monter Cancer Center, North New Hyde Park, NY, USA
| | - Matthew J Weiss
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Monter Cancer Center, North New Hyde Park, NY, USA
| | - Danielle K DePeralta
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Monter Cancer Center, North New Hyde Park, NY, USA.
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24
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Wang M, Ding D, Qin T, Wang H, Liu Y, Liu J, Liu J, Zhang H, Zhao J, Wu CH, Javed A, Wolfgang C, Guo S, Chen Q, Zhao W, Shi W, Zhu F, Guo X, Li X, He R, Xu S, Edil B, Tien YW, Jin G, Zheng L, He J, Qin R. New staging classification for pancreatic neuroendocrine neoplasms combining TNM stage and WHO grade classification []. Cancer Lett 2021; 518:207-213. [PMID: 34271105 DOI: 10.1016/j.canlet.2021.07.018] [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: 04/28/2021] [Revised: 06/25/2021] [Accepted: 07/10/2021] [Indexed: 10/20/2022]
Abstract
AJCC TNM stage and WHO grade (G) are two widely used staging systems to guide clinical management for pancreatic neuroendocrine neoplasms (panNENs), based on clinical staging and pathological grading information, respectively. We proposed to integrate TNM stage and G grade into one staging system (TNMG) and to evaluate its clinical application as a prognostic indicator for panNENs. Accordingly, 5254 patients diagnosed with panNENs were used to evaluate and to validate the applicability of TNMG to panNENs. The predictive accuracy of TNMG system was compared with that of each separate staging/grading system. We found that TNM stage and G grade were independent risk factors for survival in both the Surveillance, Epidemiology, and End Result (SEER) and multicenter series. The interaction effect between TNM stage and G grade was significant. Twelve subgroups combining the TNM stage and G grade were proposed in the TNMG stage, which were classified into five stages TNMG. According to the TNMG staging classification in the SEER series, the estimated median survival for stages I, II, III, IV, and V were 203, 174, 112, 61, and 8 months, respectively. The predictive accuracy of TNMG stage was higher than that of TNM stage and G grade used independently. The TNMG stage classification was more accurate in predicting panNEN patient's prognosis than either the TNM stage or G grade.
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Affiliation(s)
- Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Ding Ding
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Tingting Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Hebin Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, China
| | - Jianhua Liu
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China
| | - Jun Liu
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong, 250000, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Junfang Zhao
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Chien-Hui Wu
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei, 10002, Taiwan
| | - Ammar Javed
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Christopher Wolfgang
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Shiwei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai, 200433, China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, China
| | - Weihong Zhao
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China
| | - Wei Shi
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong, 250000, China
| | - Feng Zhu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Xingjun Guo
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Xu Li
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Ruizhi He
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Simiao Xu
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Barish Edil
- Department of Surgery, University of Oklahoma, Oklahoma City, OK, 73104, USA
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei, 10002, Taiwan
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai, 200433, China
| | - Lei Zheng
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Jin He
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
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Fazio N, Spada F, Bertani E. Looking for the right TNM staging system for pancreatic neuroendocrine tumors. Hepatobiliary Surg Nutr 2021; 10:382-384. [PMID: 34159169 PMCID: PMC8188133 DOI: 10.21037/hbsn-2021-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 01/20/2021] [Indexed: 01/14/2023]
Affiliation(s)
- Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Emilio Bertani
- Division of Digestive Surgery, European Institute of Oncology, IEO, IRCCS, Milan, Italy
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Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms. Pancreatology 2021; 21:779-786. [PMID: 33714670 DOI: 10.1016/j.pan.2021.02.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 02/21/2021] [Accepted: 02/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND /Objectives: Identifying reliable pretreatment imaging biomarkers for pancreatic neuroendocrine neoplasm (PanNEN) is a key imperative. Extracellular volume (ECV) fraction quantified with equilibrium contrast-enhanced CT can be easily integrated into routine examinations. This study aimed to determine whether ECV fraction with equilibrium contrast-enhanced computed tomography (CECT) could predict long-term outcomes in patients with PanNEN. METHODS This study was a retrospective observational study of 80 patients pathologically diagnosed with PanNEN at a single institution. ECV fraction of the primary lesion was calculated using region-of-interest measurement within PanNEN and the aorta on unenhanced and equilibrium CECT. The impact of clinical factors and tumor ECV fraction on progression-free survival (PFS) and overall survival (OS) was assessed with univariate and multivariate analyses using Cox proportional hazards models. The correlation between WHO classification and tumor ECV fraction was evaluated using Kendall rank correlation coefficients. RESULTS PFS and OS rates were estimated as 93.4% and 94.6%, 78.7% and 86.2%, 78.7% and 77.0%, and 78.7% and 66.6% at 1, 3, 5, and 10 years, respectively. Multivariate analysis revealed that Union for International Cancer Control (UICC) stage (hazard ratio [HR] = 3.95, P = 0.003), WHO classification (HR = 12.27, P = 0.003), and tumor ECV fraction (HR = 11.93, P = 0.039) were independent predictors of PFS. Patient age (HR = 1.11, P < 0.001), UICC stage (HR = 3.14, P = 0.001), and tumor ECV fraction (HR = 5.27, P = 0.024) were independent significant variables for predicting OS. Tumor ECV fraction had a weak inverse relationship with WHO classification (P = 0.045, τ = -0.178). CONCLUSIONS ECV fraction determined by equilibrium CECT and UICC stage may predict survival in patients with PanNEN.
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Liao X, Zhang D. The 8th Edition American Joint Committee on Cancer Staging for Hepato-pancreato-biliary Cancer: A Review and Update. Arch Pathol Lab Med 2021; 145:543-553. [PMID: 32223559 DOI: 10.5858/arpa.2020-0032-ra] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2020] [Indexed: 02/06/2023]
Abstract
CONTEXT.— Cancer staging provides critical information for patients and treating physicians to battle against cancer, predict prognosis, and guide treatment decisions. The American Joint Committee on Cancer (AJCC) staging system uses a tumor, node, metastasis (TNM) scoring algorithm and is the foremost classification system for adult cancers. This system is updated every 6 to 8 years to allow sufficient time for implementation of changes and for relevant examination and discussion of data validating those changes in staging. OBJECTIVE.— To review the updates in the 8th edition American Joint Committee on Cancer staging system on hepato-pancreato-biliary cancer. DATA SOURCES.— Literature review. CONCLUSIONS.— The 8th edition, published in 2016 and implemented on January 1, 2018, has been in use for approximately 3 years. Compared with the 7th edition, some of the changes are quite radical. This review aims to provide a summary of the changes/updates of the 8th edition with focus on hepato-pancreato-biliary cancers, and evaluate its performance through literature review.
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Affiliation(s)
- Xiaoyan Liao
- From the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York
| | - Dongwei Zhang
- From the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York
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Insights of Outcome after Resection of Small Nonfunctioning Neuroendocrine Pancreatic Tumors. Gastroenterol Res Pract 2021; 2021:6650386. [PMID: 33986797 PMCID: PMC8093048 DOI: 10.1155/2021/6650386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 03/16/2021] [Accepted: 04/17/2021] [Indexed: 11/18/2022] Open
Abstract
Background The incidence of small nonfunctioning neuroendocrine pancreatic tumors (NF-PNETs) has been increasing systematically in the last few decades. Surgical resection was once considered the treatment of choice but has been questioned in the direction of a more conservative approach for selected patients. Our aim was to analyze the outcome of surgical resection of small (≤3cm) NF-PNETs. Methods We retrospectively evaluated 14 patients with sporadic NF-PNETs who underwent pancreatic resection. Data were collected from patients' medical records. Results Of the 14 patients included, 35.71% were men, and the average age was 52.36 ± 20.36 years. Comorbidities were present in 92.86% of the cases. The incidence of postoperative complications was 42.86%, the 30-day mortality was zero, and the length of follow-up was 3.31 ± 3.0 years. The results of pathological evaluations revealed WHO grade I in 42.86% of cases, II in 21.43%, and neuroendocrine carcinoma in 35.71%. The median tumor size was 1.85cm (range, 0.5–3cm), and 2 cases had synchronous metastasis. The median TNM stage was IIa (range, I–IV). The disease-free and patient survival rates were 87.5% and 100% at 3 years and 43.75% and 75% at 10 years, respectively. The tumor pathological grade was significantly higher in head tumors than body-tail tumors, but there were no differences with respect to tumor size and TNM staging. Conclusion A surgical approach to treat small sporadic NF-PNETs is safe with low mortality and high patient survival. Based on these data, small pancreatic head tumors can be more aggressive, suggesting that surgical resection is still the best option to treat small nonfunctioning PNETS. Thus, conservative treatment should be indicated very cautiously for only cases with absolute contraindications for surgery.
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Lam AKY, Ishida H. Pancreatic neuroendocrine neoplasms: Clinicopathological features and pathological staging. Histol Histopathol 2021; 36:367-382. [PMID: 33305819 DOI: 10.14670/hh-18-288] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The nomenclature and classification of pancreatic neuroendocrine neoplasms has evolved in the last 15 years based on the advances in knowledge of the genomics, clinical behaviour and response to therapies. The current 2019 World Health Organization classification of pancreatic neuroendocrine neoplasms categorises them into three groups; pancreatic neuroendocrine tumours (PanNETs)(grade 1 grade 2, grade 3), pancreatic neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) based on the mitotic rate, Ki-67 index, morphological differentiation and/or co-existing tissue subtype. PanNETs are also classified into non-functional NET, insulinoma, gastrinoma, VIPoma, glucagonoma, somatostatinoma, ACTH-producing NET and serotonin producing NET based on hormone production and clinical manifestations. A portion of the cases were associated with genetic syndromes such as multiple neuroendocrine neoplasia 1 (MEN 1), neurofibromatosis and Von Hippel-Lindau syndrome. In view of the distinctive pathology and clinical behaviour of PanNENs, the current 8th AJCC/UICC staging system has separated prognostic staging grouping for PanNETs from the pancreatic neuroendocrine carcinomas or MiNENs. Pancreatic neuroendocrine carcinomas and MiNENs are staged according to the prognostic stage grouping for exocrine pancreatic carcinoma. The new stage grouping of PanNETs was validated to have survival curves separated between different prognostic groups. This refined histological and staging would lead to appropriate selections of treatment strategies for the patients with pancreatic neuroendocrine neoplasms.
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Affiliation(s)
| | - Hirotaka Ishida
- School of Medicine, Griffith University, Gold Coast, QLD, Australia
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Surgical Strategy Based on Radiological 3D Reconstruction in a Giant Metastatic Neuroendocrine Tumor of the Pancreas: A Case Report of an Interdisciplinary Approach. Case Rep Surg 2021; 2021:8811155. [PMID: 33564486 PMCID: PMC7850824 DOI: 10.1155/2021/8811155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 12/14/2020] [Accepted: 12/24/2020] [Indexed: 11/30/2022] Open
Abstract
Background Neuroendocrine tumors (NETs) are a rare entity and are most commonly found in the gastroenteropancreatic tract. The clinical outcome depends on the potential resectability, grade, and stage. Here, we report a case of a tumor debulking in a metastatic NET of the pancreas. A 25-year-old woman with stable metastatic NET of the pancreas G2 T4N1M1 (hepatic, extrahepatic) already underwent several therapies. Case Presentation. A 25-year-old woman with stable metastatic NET of the pancreas G2 T4N1M1 (hepatic, extrahepatic) already underwent several pharmaceutical therapies. Due to the young age, the G2 characteristic, and the stable liver disease, the decision for debulking was made. Based on a 3D CT scan, an embolization was successfully performed directly prior to a pylorus-preserving pancreatic head resection, advanced interaortocaval lymph node dissection, and an atypical liver resection within segment VI. Histological workup revealed a stage pT3, G2, pN1 (29/34), pM1c (hepatic and extrahepatic), L1, V0, Pn0 with complete surgical resection of the primary tumor (180 mm). The excision of the liver segment V showed a completely resected metastasis. Conclusions In this patient, extensive surgery of a pancreatic NET with the aim of a prolonged progression-free survival was performed. Close cooperation between different disciplines is absolutely mandatory. Modern imaging allowed a precise therapy plan to be worked out.
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Titan AL, Norton JA, Fisher AT, Foster DS, Harris EJ, Worhunsky DJ, Worth PJ, Dua MM, Visser BC, Poultsides GA, Longaker MT, Jensen RT. Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors. JAMA Netw Open 2020; 3:e2024318. [PMID: 33146734 PMCID: PMC7643030 DOI: 10.1001/jamanetworkopen.2020.24318] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need. OBJECTIVE To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs. DESIGN, SETTING, AND PARTICIPANTS This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution. Data collection occurred from 2003 to 2018. Data analysis was performed in August 2019. MAIN OUTCOMES AND MEASURES Disease-free survival (primary outcome) and overall mortality (secondary outcome) were assessed with Kaplan-Meier analysis. Recurrence risk (secondary outcome, defined as identification of tumor recurrence on imaging) was assessed with Cox proportional hazard models adjusting for covariates. RESULTS In this case series, 99 patients with locally advanced nondistant metastatic PNET (56 men [57%]) with a mean (SEM) age of 57.0 (1.4) years and a mean (SEM) follow-up of 5.3 (0.1) years underwent surgically aggressive resections. Of those, 4 patients (4%) underwent preoperative neoadjuvant treatment (including peptide receptor radionuclide therapy and chemotherapy); 18 patients (18%) underwent pancreaticoduodenectomy, 68 patients (69%) had distal or subtotal pancreatic resection, 10 patients (10%) had total resection, and 3 patients (3%) had other pancreatic procedures. Additional organ resection was required in 86 patients (87%): spleen (71 patients [71%]), major blood vessel (17 patients [17%]), bowel (2 patients [2%]), stomach (4 patients [4%]), and kidney (2 patients [2%]). Five-year disease-free survival was 61% (61 patients) and 5-year overall survival was 91% (91 patients). Of those living, 75 patients (76%) had an Eastern Cooperative Oncology Group score of less than or equal to 1 at last followup. Lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P < .001), additional organ resected (HR, 6.15; 95% CI, 1.61-23.55; P = .008), and male sex (HR, 3.77; 95% CI, 1.68-8.97; P = .003) were associated with increased risk of recurrence. Functional tumors had a lower risk of recurrence (HR, 0.23; CI, 0.06-0.89; P = .03). Required resection of blood vessels was not associated with a significant increase recurrence risk. CONCLUSIONS AND RELEVANCE In this case series, positive lymph node involvement and resection of organs with tumor involvement were associated with an increased recurrence risk. These subgroups may require adjuvant systemic treatment. These findings suggest that patients with locally advanced PNETs who undergo surgical resection have excellent disease-free and overall survival.
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Affiliation(s)
- Ashley L. Titan
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Jeffrey A. Norton
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Andrea T. Fisher
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Deshka S. Foster
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - E. John Harris
- Department of Surgery, Stanford University Hospital, Stanford, California
| | | | - Patrick J. Worth
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Monica M. Dua
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Brendan C. Visser
- Department of Surgery, Stanford University Hospital, Stanford, California
| | | | | | - Robert T. Jensen
- Gastrointestinal Cell Biology Section, National Institutes of Health, Bethesda, Maryland
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Khanna L, Prasad SR, Sunnapwar A, Kondapaneni S, Dasyam A, Tammisetti VS, Salman U, Nazarullah A, Katabathina VS. Pancreatic Neuroendocrine Neoplasms: 2020 Update on Pathologic and Imaging Findings and Classification. Radiographics 2020; 40:1240-1262. [PMID: 32795239 DOI: 10.1148/rg.2020200025] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show characteristic clinical, histomorphologic, and prognostic features; genetic alterations; and biologic behavior. Up to 10% of panNENs develop in patients with syndromes that predispose them to cancer, such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, tuberous sclerosis complex, neurofibromatosis type 1, and glucagon cell adenomatosis. PanNENs are classified as either functioning tumors, which manifest early because of clinical symptoms related to increased hormone production, or nonfunctioning tumors, which often manifest late because of mass effect. PanNENs are histopathologically classified as well-differentiated pancreatic neuroendocrine tumors (panNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (panNECs) according to the 2010 World Health Organization (WHO) classification system. Recent advances in cytogenetics and molecular biology have shown substantial heterogeneity in panNECs, and a new tumor subtype, well-differentiated, high-grade panNET, has been introduced. High-grade panNETs and panNECs are two distinct entities with different pathogenesis, clinical features, imaging findings, treatment options, and prognoses. The 2017 WHO classification system and the eighth edition of the American Joint Committee on Cancer staging system include substantial changes. Multidetector CT, MRI, and endoscopic US help in anatomic localization of the primary tumor, local-regional spread, and metastases. Somatostatin receptor scintigraphy and fluorine 18-fluorodeoxyglucose PET/CT are helpful for functional and metabolic assessment. Knowledge of recent updates in the pathogenesis, classification, and staging of panNENs and familiarity with their imaging findings allow optimal patient treatment. ©RSNA, 2020.
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Affiliation(s)
- Lokesh Khanna
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Srinivasa R Prasad
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Abhijit Sunnapwar
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Sainath Kondapaneni
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Anil Dasyam
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Varaha S Tammisetti
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Umber Salman
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Alia Nazarullah
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Venkata S Katabathina
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
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Chen HY, Zhou YL, Chen YH, Wang X, Zhang H, Ke NW, Liu XB, Tan CL. Functionality is not an independent prognostic factor for pancreatic neuroendocrine tumors. World J Gastroenterol 2020; 26:3638-3649. [PMID: 32742132 PMCID: PMC7366052 DOI: 10.3748/wjg.v26.i25.3638] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 05/08/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic neuroendocrine neoplasms (pNENs) that produce hormones leading to symptoms are classified as functional tumors, while others are classified as nonfunctional tumors. The traditional view is that functionality is a factor that affects the prognosis of pNEN patients. However, as the sample sizes of studies have increased, researches in recent years have proposed new viewpoints. AIM To assess whether functionality is an independent factor for predicting the prognosis of pNEN patients. METHODS From January 2004 to December 2016, data of patients who underwent surgery at the primary site for the treatment of pNENs from the Surveillance, Epidemiology, and End Results (SEER) database and West China Hospital database were retrospectively analyzed. RESULTS Contemporaneous data from the two databases were analyzed separately as two cohorts and then merged as the third cohort to create a large sample that was suitable for multivariate analysis. From the SEER database, age (P = 0.006) and T stage (P < 0.001) were independent risk factors affecting the survival. From the West China Hospital database, independent prognostic factors were age (P = 0.034), sex (P = 0.032), and grade (P = 0.039). The result of the cohort consisting of the combined populations from the two databases showed that race (P = 0.015), age (P = 0.002), sex (P = 0.032) and T stage (P < 0.001) were independent prognostic factors. In the West China Hospital database and in the total population, nonfunctional pNETs and other functional pNETs tended to have poorer prognoses than insulinoma. However, functionality was not associated with the survival time of patients with pNETs in the multivariate analysis. CONCLUSION Functionality is not associated with prognosis. Race, age, sex, and T stage are independent factors for predicting the survival of patients with pNETs.
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Affiliation(s)
- Hong-Yu Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ya-Liang Zhou
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yong-Hua Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xing Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hao Zhang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Neng-Wen Ke
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xu-Bao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Chun-Lu Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Ma ZY, Gong YF, Zhuang HK, Zhou ZX, Huang SZ, Zou YP, Huang BW, Sun ZH, Zhang CZ, Tang YQ, Hou BH. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26:2305-2322. [PMID: 32476795 PMCID: PMC7243647 DOI: 10.3748/wjg.v26.i19.2305] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/27/2020] [Accepted: 04/27/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.
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Affiliation(s)
- Zu-Yi Ma
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Yuan-Feng Gong
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Hong-Kai Zhuang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Zi-Xuan Zhou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Shan-Zhou Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yi-Ping Zou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Bo-Wen Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Zhong-Hai Sun
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Chuan-Zhao Zhang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yun-Qiang Tang
- Department of Hepatobiliary Surgery, the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Hua Hou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
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Lee L, Ito T, Jensen RT. Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies. Expert Rev Anticancer Ther 2019; 19:1029-1050. [PMID: 31738624 PMCID: PMC6923565 DOI: 10.1080/14737140.2019.1693893] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 11/13/2019] [Indexed: 02/06/2023]
Abstract
Introduction: Recent advances in diagnostic modalities and therapeutic agents have raised the importance of prognostic factors in predicting overall survival, as well as predictive factors for surgical outcomes, in tailoring therapeutic strategies of patients with pancreatic neuroendocrine neoplasms (panNENs).Areas covered: Numerous recent studies of panNEN patients report the prognostic values of a number of clinically related factors (clinical, laboratory, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors on long-term survival. In addition, an increasing number of studies showed the usefulness of various factors, specifically biomarkers and molecular makers, in predicting recurrence and mortality related to surgical treatment. Recent findings (from the last 3 years) in each of these areas, as well as recent controversies, are reviewed.Expert commentary: The clinical importance of prognostic and predictive factors for panNENs is markedly increased for both overall outcome and post resection, as a result of recent advances in all aspects of the diagnosis, management and treatment of panNENs. Despite the proven prognostic utility of routinely used tumor grading/classification and staging systems, further studies are required to establish these novel prognostic factors to support their routine clinical use.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, 20892-1804, USA
- Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan
| | - Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, Fukuoka, 814-0001, Japan
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, 20892-1804, USA
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