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Song YJ, Lim JK, Choi JH. Role of endoscopic ultrasound in the diagnosis and local ablative therapy of pancreatic neuroendocrine tumors. Korean J Intern Med 2025; 40:170-180. [PMID: 39995262 PMCID: PMC11938681 DOI: 10.3904/kjim.2024.293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 02/26/2025] Open
Abstract
Advancements in diagnostic technology have led to the improved detection of pancreatic neuroendocrine tumors (PNETs) and thus to an increase in the number of reported cases. Endoscopic ultrasound (EUS) technology, including in combination with contrast-enhanced harmonic imaging, aids in distinguishing PNETs from other tumors, while EUS-guided fine-needle aspiration or biopsy has improved the histological diagnosis and grading of tumors. The recent introduction of EUS-guided ablation using ethanol injection or radiofrequency ablation has offered an alternative to surgery in the management of PNETs. Comparisons with surgery have shown similar outcomes but fewer adverse effects. Although standardized protocols and prospective studies with long-term follow-up are still needed, EUS-based methods are promising approaches that can contribute to a better quality of life for PNET patients.
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Affiliation(s)
- Yun Je Song
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
| | - Jun Kyeong Lim
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
| | - Jun-Ho Choi
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
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López Gonzalez M, Hernando-Requejo O, Ciervide Jurío R, Montero Luis Á, Saiz Guisasola C, Sánchez Saugar E, Álvarez Rodríguez B, Chen-Zhao X, García-Aranda M, Valero Albarran J, Alonso Gutierrez R, García Cañamaque L, Prados S, Quijano Y, de Vicente E, Rubio C. Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis. Clin Transl Oncol 2025; 27:377-385. [PMID: 38907097 DOI: 10.1007/s12094-024-03538-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/24/2024] [Indexed: 06/23/2024]
Abstract
INTRODUCTION Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.
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Affiliation(s)
- Mercedes López Gonzalez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain.
| | - Ovidio Hernando-Requejo
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Raquel Ciervide Jurío
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Ángel Montero Luis
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Carmen Saiz Guisasola
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Emilio Sánchez Saugar
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Beatriz Álvarez Rodríguez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Xin Chen-Zhao
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Mariola García-Aranda
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Jeannette Valero Albarran
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Rosa Alonso Gutierrez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Lina García Cañamaque
- Department of Nuclear Medicine, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Susana Prados
- Department of Gastroenterology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Yolanda Quijano
- Department of Surgery, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Emilio de Vicente
- Department of Surgery, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Carmen Rubio
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
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Izumo W, Higuchi R, Furukawa T, Shiihara M, Uemura S, Yazawa T, Yamamoto M, Honda G. The importance of microvascular invasion in patients with non-functioning pancreatic neuroendocrine neoplasm. Langenbecks Arch Surg 2024; 410:8. [PMID: 39676094 DOI: 10.1007/s00423-024-03563-x] [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: 07/05/2024] [Accepted: 11/29/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND/OBJECTIVES The oncological importance of lymphatic, microvascular, and perineural invasions and their association with outcomes in patients with non-functioning pancreatic neuroendocrine neoplasm (NF-PanNEN) remains unclear. We aimed to investigate the role of these factors in the prognosis of patients with NF-PanNEN. METHODS We retrospectively analyzed 115 patients who underwent curative resection and were pathologically and clinically diagnosed with NF-PanNEN. We evaluated the relationship between clinicopathological factors and recurrence. RESULTS Thirty (26%), 38 (33%), and 11 (10%) patients had lymphatic, microvascular, and nerve invasions, respectively. Twenty-one patients (18%) experienced recurrence, with a median time to recurrence of 2.6 years (range: 0.3-8.2). The 3-, 5-, and 10-year recurrence-free survival (RFS) rates were 88.3%, 84.4%, and 79.1%, respectively. In multivariate analyses, World Health Organization Grade G2-3 (vs. G1, hazard ratio (HR): 16.2), T factor T3-4 (vs. T1-2, HR: 5.2), and the presence of microvascular invasion (vs. absence, HR: 5.6) were significant risk factors for RFS. When these risk factors were assigned as risk score of three, one, and one points depending on the HR, the 5-year recurrence rates in patients with risk score groups 0-1 and 2-5 were 98.6% and 53.3%, (P < 0.001). Moreover, only the presence of microvascular invasion significantly increased the likelihood of recurrence within 3 years. CONCLUSIONS The presence of microvascular invasion is an independent risk factor for recurrence in patients with NF-PanNEN. Our risk scoring system, which includes "the presence of microvascular invasion," may be useful for predicting recurrence.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Womens Medical University, 8-1 Kawada-cho, Tokyo, Shinjuku City, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Womens Medical University, 8-1 Kawada-cho, Tokyo, Shinjuku City, Japan.
- Division of Gastroenterological Surgery, Tokyo Womens Medical University Yachiyo Medical Center, Yachiyo City, Chiba, Japan.
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Womens Medical University, 8-1 Kawada-cho, Tokyo, Shinjuku City, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Womens Medical University, 8-1 Kawada-cho, Tokyo, Shinjuku City, Japan
| | - Takehisa Yazawa
- Gastrointestinal surgery, Utsunomiya Memorial Hospital, Utsunomiya, Japan
| | - Masakazu Yamamoto
- Gastrointestinal surgery, Utsunomiya Memorial Hospital, Utsunomiya, Japan
| | - Goro Honda
- Department of Surgery, Institute of Gastroenterology, Tokyo Womens Medical University, 8-1 Kawada-cho, Tokyo, Shinjuku City, Japan
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Gao H, Zhang W, Li Z, Liu W, Liu M, Zhuo Q, Shi Y, Xu W, Zhou C, Qin Y, Xu J, Chen J, Yu X, Xu X, Ji S. Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide. BMC Cancer 2024; 24:1362. [PMID: 39511555 PMCID: PMC11542389 DOI: 10.1186/s12885-024-13117-5] [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: 06/03/2024] [Accepted: 10/28/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). METHOD Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. RESULTS In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001). CONCLUSION Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.
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Affiliation(s)
- Heli Gao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wuhu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Zheng Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wensheng Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Mengqi Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Qifeng Zhuo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yihua Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Chenjie Zhou
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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Liu YL, Zhu HB, Chen ML, Sun W, Li XT, Sun YS. Prediction of the lymphatic, microvascular, and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging. World J Gastrointest Surg 2023; 15:2809-2819. [PMID: 38222000 PMCID: PMC10784819 DOI: 10.4240/wjgs.v15.i12.2809] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/06/2023] [Accepted: 12/06/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Significant correlation between lymphatic, microvascular, and perineural invasion (LMPI) and the prognosis of pancreatic neuroendocrine tumors (PENTs) was confirmed by previous studies. There was no previous study reported the relationship between magnetic resonance imaging (MRI) parameters and LMPI. AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs (NFPNETs). METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study. The patients were divided into group 1 (n = 34, LMPI negative) and group 2 (n = 27, LMPI positive). The clinical characteristics and qualitative MRI features were collected. In order to predict LMPI status in NF-PNETs, a multivariate logistic regression model was constructed. Diagnostic performance was evaluated by calculating the receiver operator characteristic (ROC) curve with area under ROC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS There were significant differences in the lymph node metastasis stage, tumor grade, neuron-specific enolase levels, tumor margin, main pancreatic ductal dilatation, common bile duct dilatation, enhancement pattern, vascular and adjacent tissue involvement, synchronous liver metastases, the long axis of the largest lymph node, the short axis of the largest lymph node, number of the lymph nodes with short axis > 5 or 10 mm, and tumor volume between two groups (P < 0.05). Multivariate analysis showed that tumor margin (odds ratio = 11.523, P < 0.001) was a predictive factor for LMPI of NF-PNETs. The area under the receiver value for the predictive performance of combined predictive factors was 0.855. The sensitivity, specificity, PPV, NPV and accuracy of the model were 48.1% (14/27), 97.1% (33/34), 97.1% (13/14), 70.2% (33/47) and 0.754, respectively. CONCLUSION Using preoperative MRI, ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.
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Affiliation(s)
- Yu-Liang Liu
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Hai-Bin Zhu
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Mai-Lin Chen
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Wei Sun
- Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiao-Ting Li
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ying-Shi Sun
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing 100142, China
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Gangi A, Ferrone CR. What Is the Role of Lymph Node Resections in Small Islet Tumors? Adv Surg 2023; 57:47-58. [PMID: 37536861 DOI: 10.1016/j.yasu.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Well-differentiated nonfunctional pancreatic neuroendocrine tumors are often indolent neoplasms without lymph node (LN) metastasis at diagnosis. Patients with PNETs that are functional or >2 cm should have surgical resection as per the standard of care. However, in appropriately selected patients with NF PNETs <2 cm who are at low risk of LN metastasis, the extent of surgery and lymphadenectomy could be limited.
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Affiliation(s)
- Alexandra Gangi
- Gastrointestinal Tumor Program, Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard North Tower, Suite 8215, Los Angeles, CA 90048, USA.
| | - Cristina R Ferrone
- Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard North Tower, Suite 8215, Los Angeles, CA 90048, USA
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Ciocan RA, Graur F, Ciocan A, Cismaru CA, Pintilie SR, Berindan-Neagoe I, Hajjar NA, Gherman CD. Robot-Guided Ultrasonography in Surgical Interventions. Diagnostics (Basel) 2023; 13:2456. [PMID: 37510199 PMCID: PMC10378616 DOI: 10.3390/diagnostics13142456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
INTRODUCTION The introduction of robotic-guided procedures in surgical techniques has brought an increase in the accuracy and control of resections. Surgery has evolved as a technique since the development of laparoscopy, which has added to the visualisation of the peritoneal cavity from a different perspective. Multi-armed robot associated with real-time intraoperative imaging devices brings important manoeuvrability and dexterity improvements in certain surgical fields. MATERIALS AND METHODS The present study is designed to synthesise the development of imaging techniques with a focus on ultrasonography in robotic surgery in the last ten years regarding abdominal surgical interventions. RESULTS All studies involved abdominal surgery. Out of the seven studies, two were performed in clinical trials. The other five studies were performed on organs or simulators and attempted to develop a hybrid surgical technique using ultrasonography and robotic surgery. Most studies aim to surgically identify both blood vessels and nerve structures through this combined technique (surgery and imaging). CONCLUSIONS Ultrasonography is often used in minimally invasive surgical techniques. This adds to the visualisation of blood vessels, the correct identification of tumour margins, and the location of surgical instruments in the tissue. The development of ultrasound technology from 2D to 3D and 4D has brought improvements in minimally invasive and robotic surgical techniques, and it should be further studied to bring surgery to a higher level.
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Affiliation(s)
- Răzvan Alexandru Ciocan
- Department of Surgery-Practical Abilities, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania
| | - Florin Graur
- Department of Surgery, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Croitorilor Street, No. 19-21, 400162 Cluj-Napoca, Romania
| | - Andra Ciocan
- Department of Surgery, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Croitorilor Street, No. 19-21, 400162 Cluj-Napoca, Romania
| | - Cosmin Andrei Cismaru
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Victor Babeș Street, No. 8, 400347 Cluj-Napoca, Romania
| | - Sebastian Romeo Pintilie
- "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Victor Babeș Street, No. 8, 400347 Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Victor Babeș Street, No. 8, 400347 Cluj-Napoca, Romania
| | - Nadim Al Hajjar
- Department of Surgery, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Croitorilor Street, No. 19-21, 400162 Cluj-Napoca, Romania
| | - Claudia Diana Gherman
- Department of Surgery-Practical Abilities, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania
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Rossi G, Petrone MC, Healey AJ, Arcidiacono PG. Approaching Small Neuroendocrine Tumors with Radiofrequency Ablation. Diagnostics (Basel) 2023; 13:diagnostics13091561. [PMID: 37174952 PMCID: PMC10177414 DOI: 10.3390/diagnostics13091561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/20/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
In recent years, small pancreatic neuroendocrine tumors (pNETs) have shown a dramatic increase in terms of incidence and prevalence, and endoscopic ultrasound (EUS) radiofrequency ablation (RFA) is one potential method to treat the disease in selected patients. As well as the heterogeneity of pNET histology, the studies reported in the literature on EUS-RFA procedures for pNETs are heterogeneous in terms of ablation settings (particularly ablation powers), radiological controls, and radiological indications. The aim of this review is to report the current reported experience in EUS-RFA of small pNETs to help formulate the procedure indications and ablation settings. Another aim is to evaluate the timing and the modality of the radiological surveillance after the ablation. Moreover, new studies on large-scale series are needed in terms of the safety and long-term oncological efficacy of RFA on these small lesions.
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Affiliation(s)
- Gemma Rossi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Maria Chiara Petrone
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Andrew J Healey
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, 20132 Milan, Italy
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Merchant AA, Goebel AM, Willingham FF. Radiofrequency ablation for the management of pancreatic mass lesions. Curr Opin Gastroenterol 2023:00001574-990000000-00066. [PMID: 37097824 DOI: 10.1097/mog.0000000000000939] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
PURPOSE OF REVIEW Patients with pancreatic tumors may have limited treatment options. Pancreatic tumor ablation is a novel and emerging treatment modality which can now be performed using endoscopic ultrasound (EUS) guidance. This modality is well suited to guide energy delivery for radiofrequency ablation (RFA) and microwave ablation. These approaches provide minimally invasive, nonsurgical methods for delivering energy to ablate pancreatic tumors in situ. This review summarizes the current data and safety profile for ablation in managing pancreatic cancer and pancreatic neuroendocrine tumors. RECENT FINDINGS RFA uses thermal energy to induce cell death by coagulative necrosis and protein denaturation. Studies have reported increased overall survival in patients with pancreatic tumors treated with EUS-guided RFA in a multimodality systemic approach and when used in palliative surgeries. Radiofrequency ablation may have corollary benefits in inducing an immune-modulatory effect. Tumor marker carbohydrate antigen 19-9 has been reported to decrease in response to RFA. Microwave ablation is an emerging modality. SUMMARY RFA utilizes focal thermal energy to induce cell death. RFA has been applied through open, laparoscopic, and radiographic modalities. EUS-guided approaches are now allowing RFA and microwave ablation to be performed for pancreatic tumors in situ.
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Affiliation(s)
| | - Anna M Goebel
- Emory University School of Medicine, Emory University
| | - Field F Willingham
- Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, Georgia, USA
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Karaisz FG, Elkelany OO, Davies B, Lozanski G, Krishna SG. A Review on Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of Pancreatic Lesions. Diagnostics (Basel) 2023; 13:diagnostics13030536. [PMID: 36766643 PMCID: PMC9914142 DOI: 10.3390/diagnostics13030536] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/27/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023] Open
Abstract
The morbidity associated with pancreatectomies limits surgical options for high-risk patients with pancreatic neoplasms that warrant resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) offers a minimally invasive and potentially definitive means to treat pancreatic neuroendocrine tumors and precancerous pancreatic cystic lesions. In addition, EUS-RFA may play a role in the treatment and palliation of non-surgical cases of pancreatic adenocarcinoma. The efficacy of RFA appears to be further enhanced by systemic immunomodulatory effects. Here, we review current studies on the developing role of EUS-RFA in these pancreatic pathologies.
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Affiliation(s)
- Fred G. Karaisz
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Osama O. Elkelany
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Benjamin Davies
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Gerard Lozanski
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus OH 43210, USA
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
- Correspondence:
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11
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Kurita Y, Kobayashi N, Hara K, Mizuno N, Kuwahara T, Okuno N, Haba S, Tokuhisa M, Hasegawa S, Sato T, Hosono K, Kato S, Kessoku T, Endo I, Shimizu Y, Kubota K, Nakajima A, Ichikawa Y, Niwa Y. Effectiveness and Prognostic Factors of Everolimus in Patients with Pancreatic Neuroendocrine Neoplasms. Intern Med 2023; 62:159-167. [PMID: 35705270 PMCID: PMC9908390 DOI: 10.2169/internalmedicine.9416-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types [hazard ratio (HR), 0.45; p=0.005]. A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p=0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (≤2nd; HR, 0.55; p=0.031), and presence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (≤25%; HR, 0.27; p<0.001), everolimus treatment line (≤2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005). Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.
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Affiliation(s)
- Yusuke Kurita
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
- Department of Gastroenterology, Aichi Cancer Center, Japan
| | | | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center, Japan
| | | | | | - Nozomi Okuno
- Department of Gastroenterology, Aichi Cancer Center, Japan
| | - Shin Haba
- Department of Gastroenterology, Aichi Cancer Center, Japan
| | | | - Sho Hasegawa
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
| | - Takamitsu Sato
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
| | - Kunihiro Hosono
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
| | - Shingo Kato
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
- Department of Clinical Cancer Genomics, Yokohama City University, Japan
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
- Department of Palliative Medicine, Yokohama City University, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center, Japan
| | - Kensuke Kubota
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University, Japan
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Rimbaş M, Rizzatti G, Tosoni A, Impagnatiello M, Panzuto F, Larghi A. Small nonfunctional pancreatic neuroendocrine neoplasms: Time for a step-up treatment approach? Endosc Ultrasound 2023; 12:1-7. [PMID: 36510866 PMCID: PMC10134916 DOI: 10.4103/eus-d-22-00028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Surgery has been regarded as the only curative treatment for patients with small nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) less than 2 cm. Due to the significant adverse event rates of surgery, the European Neuroendocrine Tumor Society issued guidelines favoring surveillance for those patients lacking criteria suggestive of an aggressive disease. Despite the above recommendations, a significant proportion of small NF-PNEN patients still undergo surgery. Recently, several studies have reported the safety and effectiveness of EUS-guided radiofrequency ablation (RFA) for the treatment of small NF-PNENs. The experience with EUS-RFA is, however, limited, but published results indicate a potential role as a minimally invasive alternative treatment for these patients, in particular in those in whom further progression is more probable, before they reach the absolute need for surgery. A step-up approach with EUS-RFA followed by surgery for the failure cases can become a valid option to be validated in clinical studies.
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Affiliation(s)
- Mihai Rimbaş
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Gastroenterology, Colentina Clinical Hospital; Department of Internal Medicine, Carol Davila University of Medicine, Bucharest, Romania
| | - Gianenerico Rizzatti
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alberto Tosoni
- Department of Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Michele Impagnatiello
- Department of Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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Heng X, Chen B, Zhao K, Li J, Wu W, Peng Y, Zhong R. Comparison of nomogram for Primary Nonfunctional Pancreatic Neuroendocrine Tumors based on the 7th vs 8th edition of the AJCC cancer staging manual. PLoS One 2023; 18:e0284930. [PMID: 37093837 PMCID: PMC10124865 DOI: 10.1371/journal.pone.0284930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 04/11/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Our study aimed to construct and validate prognostic nomograms for predicting survival for patients with Nonfunctional Pancreatic neuroendocrine tumor (NF-pNET). METHODS This retrospective study included 1824 patients diagnosed with NF-pNET in the Surveillance, Epidemiology and End Results database between 2004 and 2016. Randomization divided the patients into training (n = 1278) and validation (n = 546) cohorts. Prognostic factors were determined using Cox regression analyses, nomograms based on AJCC 7th and 8th staging system were constructed separately. The prediction models were validated using internal validation and external validation. RESULTS Age, year of diagnosis, primary tumor site, grade, 7th or 8th TNM stage, surgery, tumor size were determined as prognostic indicator to construct two nomograms. Harrell's concordance index (C-index) of two nomograms exhibited a clinical predictive ability of 0.828 (95%CI, 0.808~0.849) vs 0.828 (95% CI, 0.808~0.849) in the internal verification. The c-index in the external validation was 0.812 (95%CI, 0.778~0.864) vs 0.814 (95% CI, 0.779~0.848). The predictive power of the two nomograms is comparable. CONCLUSIONS Our nomogram may be a effective tool for predicting overall survival in patients with NF-pNET. The AJCC 8th-edition system provides discrimination similar to that of the 7th-edition system.
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Affiliation(s)
- Xin Heng
- Department of Respiratory and Critical Care Medicine, Chengdu Second People's Hospital, Chengdu, China
| | - Baijun Chen
- Department of Gastroenterology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Kui Zhao
- Department of Gastroenterology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jun Li
- Department of Gastroenterology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Weiyu Wu
- Department of Gastroenterology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yan Peng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Rui Zhong
- Department of Gastroenterology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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Ghezzo S, Bezzi C, Neri I, Mapelli P, Presotto L, Gajate AMS, Bettinardi V, Garibotto V, De Cobelli F, Scifo P, Picchio M. Radiomics and artificial intelligence. CLINICAL PET/MRI 2023:365-401. [DOI: 10.1016/b978-0-323-88537-9.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Tu KY, Huang YS, Lau J, Lee HH. Adaptive Tomotherapy for locally advanced unresectable pancreatic neuroendocrine tumor: Case report and literature review. Front Oncol 2022; 12:1045752. [PMID: 36452486 PMCID: PMC9702327 DOI: 10.3389/fonc.2022.1045752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 10/25/2022] [Indexed: 11/03/2023] Open
Abstract
BACKGROUND Pancreatic neuroendocrine tumor (NET) is rare, and the majority presents late in their clinical course. Here, we present a huge locally advanced pancreatic NET having Hi-Art helical Tomotherapy that resulted in a 68% reduction in target volume during adaptive image-guided radiotherapy (IGRT). CASE SUMMARY A 63-year-old man without any history of systemic disease developed voiding difficulty for several months. Associated symptoms included poor appetite, nausea, distended abdomen, and body weight loss. Further magnetic resonance imaging showed a large multilobulated tumor in the left upper abdomen. Tumor biopsy revealed well-differentiated, grade 2, neuroendocrine tumor. Complete resection was unattainable. Therefore, Lanreotide was prescribed initially. However, tumor progression up to the greatest diameter of 18 cm was noted on computed tomography 5 months later. Thus, he stopped Lanreotide and commenced on concurrent chemoradiotherapy (CCRT). With a total dose of 70 Gy in 35 fractions, we generated two adaptive treatment plans during the whole course. Laparoscopic subtotal pancreatectomy with spleen preservation was performed after neoadjuvant CCRT. It has been more than 3 years after IGRT, and he remains cancer free and reports no side effects during regular follow-ups. CONCLUSION Tomotherapy caused tumor size reduction and hence facilitated surgical possibility for this originally unresectable pancreatic NET. Neoadjuvant IGRT incorporated with adaptive treatment planning enhanced delivery accuracy. In this case of pancreatic NET resistant to Lanreotide, inter-fractional tumor regression from 1910 to 605 cc (68%) was documented.
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Affiliation(s)
- Kuan-Yi Tu
- School of Post Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yen-Shuo Huang
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Juntiong Lau
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsin-Hua Lee
- Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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Surgery, Liver Directed Therapy and Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumor Liver Metastases. Cancers (Basel) 2022; 14:cancers14205103. [PMID: 36291892 PMCID: PMC9599940 DOI: 10.3390/cancers14205103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 09/19/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are described by the World Health Organization (WHO) classification by grade (1–3) and degree of differentiation. Grade 1 and 2; well differentiated PNETs are often characterized as relatively “indolent” tumors for which locoregional therapies have been shown to be effective for palliation of symptom control and prolongation of survival even in the setting of advanced disease. The treatment of liver metastases includes surgical and non-surgical modalities with varying degrees of invasiveness; efficacy; and risk. Most of these modalities have not been prospectively compared. This paper reviews literature that has been published on treatment of pancreatic neuroendocrine liver metastases using surgery; liver directed embolization and peptide receptor radionuclide therapy (PRRT). Surgery is associated with the longest survival in patients with resectable disease burden. Liver-directed (hepatic artery) therapies can sometimes convert patients with borderline disease into candidates for surgery. Among the three embolization modalities; the preponderance of data suggests chemoembolization offers superior radiographic response compared to bland embolization and radioembolization; but all have similar survival. PRRT was initially approved as salvage therapy in patients with advanced disease that was not amenable to resection or embolization; though the role of PRRT is evolving rapidly
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Wu Z, Qiu X, Zhi Y, Shi X, Lv G. The risk and prognostic factors for G1 pancreatic neuroendocrine tumors: A retrospective analysis of the SEER database. Front Oncol 2022; 12:993524. [PMID: 36276109 PMCID: PMC9582835 DOI: 10.3389/fonc.2022.993524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/16/2022] [Indexed: 11/13/2022] Open
Abstract
Background Pancreatic neuroendocrine tumors (pNETs) are rare neuroendocrine neoplasms (NENs) for which little is known about their clinical features, treatment options, and survival prognosis. The purpose of this study is to evaluate the risk factors affecting the overall survival (OS) and cancer-specific survival (CSS) in patients with grade 1 pNETs (G1 pNETs) and to provide a new theoretical basis for clinical diagnosis and treatment. Methods A retrospective analysis of individuals with G1 pNETs registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. Risk factors affecting OS and CSS were analyzed using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model. Results A total of 751 patients were included, most of whom were white (77.2%) women (53.9%) under the age of 60 years (54.9%), of whom 66 died of pNETs (8.78%) and 34 died of other causes (4.52%). Patients who were older than 60 years at diagnosis (hazard ratio [HR] = 1.866, 95% confidence interval [CI]: 1.242-2.805) had worse OS. And stage in the regional extent (HR = 1.777, 95% CI: 1.006-3.137) or distance extent (HR = 4.540, 95% CI: 2.439-8.453) had worse OS. Patients who delayed treatment after diagnosis had shorter CSS (delayed treatment < 1 month: HR = 1.933, 95% CI: 0.863-4.333; delayed treatment ≥ 1 month: HR = 2.208; 95% CI:1.047-4.654). Patients with lymph node metastasis (HR = 1.989, 95% CI: 1.137-3.479) or distant metastasis (HR = 5.625, 95% CI: 1.892-16.726) had worse CSS. Acceptance of surgery can significantly improve the patient’s OS and CSS. OS (partial pancreatectomy [PP]: HR = 0.350, 95% CI: 0.182-0.672; pancreatectomy and duodenectomy [PD]: HR = 0.426, 95% CI: 0.222-0.815; total pancreatectomy [TP]: HR = 0.495, 95% CI: 0.193-1.267). CSS(PP: HR = 0.148, 95% CI: 0.0054-0.401; PD: HR = 0.332, 95% CI: 0.150-0.730; TP: HR = 0.69, 95% CI: 0.254-1.872). Conclusion Age and stage were identified as independent risk factors for OS. Delayed treatment, N stage and M stage were independent risk factors for CSS. Only surgery was identified as independent protective factors for OS and CSS.
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Minczeles NS, van Eijck CHJ, van Gils MJ, van Velthuysen MLF, Nieveen van Dijkum EJM, Feelders RA, de Herder WW, Brabander T, Hofland J. Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients. Eur J Nucl Med Mol Imaging 2022; 49:3203-3214. [PMID: 35230492 PMCID: PMC9250460 DOI: 10.1007/s00259-022-05734-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE induces objective response in up to 57% of pancreatic neuroendocrine neoplasms (panNENs). Therefore, PRRT may comprise a downstaging option for panNEN patients who are not eligible for upfront curative surgery or are at high risk for recurrence. The aim of this study was to assess the potency of induction PRRT for locally advanced panNENs and to evaluate the effect of surgery after PRRT on overall survival (OS). METHODS Retrospective cohort study of panNEN patients treated with induction 177Lu-DOTATATE. RESULTS After PRRT, 26 out of 49 patients underwent pancreatic surgery with curative intent (PRRT + surgery). Partial objective response was obtained in 62% of the PRRT + surgery group versus 26% of the patients not undergoing panNEN surgery (PRRT-only group, p = 0.02). Downstaging in tumour-vessel interface was observed in 38% of all patients with at least one involved vessel. Median OS was 14.7 years (95% CI 5.9-23.6) for the PRRT + surgery group compared to 5.5 years (95% CI 4.5-6.5) for the PRRT-only group (p = 0.003). In the Cox proportional hazards analysis, surgery was not significantly associated with OS after propensity score adjustment with cumulative activity, performance status, tumour size after PRRT, and tumour grade. Median progression-free survival was 5.3 years (95% CI 2.4-8.1) for the PRRT + surgery group and 3.0 years (95% CI 1.6-4.4) for the PRRT-only group (p = 0.02). CONCLUSION Early administration of PRRT followed by surgery is associated with favourable long-term outcomes in patients with locally advanced or oligometastatic panNEN and can be considered for selected patients with vascular involvement and/or increased risk of recurrence.
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Affiliation(s)
- Noémie S Minczeles
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Centre, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
- Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
| | | | - Marjon J van Gils
- Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
| | | | - Els J M Nieveen van Dijkum
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Richard A Feelders
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Centre, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands
| | - Wouter W de Herder
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Centre, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands
| | - Tessa Brabander
- Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Centre, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands
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Gudmundsdottir H, Tomlinson JL, Graham RP, Thiels CA, Warner SG, Smoot RL, Kendrick ML, Nagorney DM, Halfdanarson TR, Habermann EB, Truty MJ, Cleary SP. Outcomes of pancreatectomy with portomesenteric venous resection and reconstruction for locally advanced pancreatic neuroendocrine neoplasms. HPB (Oxford) 2022; 24:1186-1193. [PMID: 35078716 DOI: 10.1016/j.hpb.2021.12.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/15/2021] [Accepted: 12/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND While pancreatectomy with portomesenteric venous resection and reconstruction is commonly performed for locally advanced pancreatic adenocarcinoma, little is known regarding outcomes for pancreatic neuroendocrine neoplasms (panNENs). METHODS Patients who underwent non-parenchyma-sparing pancreatectomy for panNENs at Mayo Clinic from 2000 to 2020 were retrospectively reviewed. Propensity score matching was performed and patient characteristics and outcomes compared. RESULTS Of 867 eligible patients, 41 (4.7%) required vascular resection, including 38 patients who underwent portomesenteric venous resection only. Of these, 23 underwent pancreaticoduodenectomy or total pancreatectomy and 15 distal pancreatectomy. Patients who required portomesenteric venous resection had larger tumors, higher tumor grade, and higher disease stage. After propensity score matching to patients undergoing standard resection, the portomesenteric venous resection group had longer operative times, greater blood loss, and higher transfusion rates. While portomesenteric venous thrombosis was more common after venous resection, major complication rates and perioperative mortality were similar between the two groups, as were 5-year overall and progression-free survival. CONCLUSION For patients with locally advanced panNENs, pancreatectomy with portomesenteric venous resection and reconstruction can be performed in selected patients at high-volume centers with acceptable perioperative morbidity and short- and long-term survival.
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Affiliation(s)
| | | | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Rory L Smoot
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | | | - Elizabeth B Habermann
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN, USA
| | - Mark J Truty
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Sean P Cleary
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
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Yang Z, Liang J, Leng K, Shi G. Survival Benefit of Surgical Resection for Pancreatic Neuroendocrine Tumors With Oligometastatic Liver Metastasis: A Retrospective and Propensity Score-Matching Analysis. Front Oncol 2022; 12:903560. [PMID: 35847865 PMCID: PMC9279685 DOI: 10.3389/fonc.2022.903560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/18/2022] [Indexed: 11/22/2022] Open
Abstract
Background Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of pancreatic malignancies. Surgical resection is the only curative treatment option for patients with localized PanNETs, yet the role of cancer-directed surgery (CDS) in the setting of oligometastatic liver metastasis remains a controversy. Methods All patients diagnosed with PanNETs and liver-only metastasis from 2010 to 2018 were identified from the SEER database. The biases of baseline characteristics between CDS and no-CDS cohorts were reduced by the propensity score-matching (PSM) method, and the prognostic role of CDS was estimated using the Kaplan–Meier method and Cox regression models. Logistic regression analysis was utilized to identify factors associated with patients who underwent CDS. Results A total of 1,270 PanNET patients with oligometastatic liver metastasis were included and analyzed. Of these patients, 283 (22.3%) patients underwent CDS of the primary tumor, while the remaining 987 (77.7%) did not. The OS and CSS were significantly better in the CDS cohort regardless of the propensity score analysis. Multivariate analysis revealed that age, tumor differentiation, tumor location, and lymph node status were significantly associated with patients who were more likely to receive CDS. Conclusion Our study demonstrated that CDS was associated with survival benefits in selected patients with PanNETs and liver-only metastasis based on a large population database.
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Nießen A, Bechtiger FA, Hinz U, Lewosinska M, Billmann F, Hackert T, Büchler MW, Schimmack S. Enucleation Is a Feasible Procedure for Well-Differentiated pNEN-A Matched Pair Analysis. Cancers (Basel) 2022; 14:cancers14102570. [PMID: 35626174 PMCID: PMC9139922 DOI: 10.3390/cancers14102570] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 02/05/2023] Open
Abstract
The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001−2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95−170) versus 263 (172−337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7−11) versus 10 (8−17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.
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22
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Shi J, Liu S, Cao J, Shan S, Ren C, Zhang J, Wang Y. Prognostic Nomogram Based on the Metastatic Lymph Node Ratio for T 1-4N 0-1M 0 Pancreatic Neuroendocrine Tumors After Surgery. Front Oncol 2022; 12:899759. [PMID: 35574346 PMCID: PMC9092648 DOI: 10.3389/fonc.2022.899759] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 03/31/2022] [Indexed: 11/25/2022] Open
Abstract
Purpose This study aimed to investigate the prognostic significance of the metastatic lymph node ratio (LNR) in patients with pancreatic neuroendocrine tumors (pNETs) and to develop and validate nomograms to predict 5-, 7-, and 10-year overall survival (OS) and cancer-specific survival (CSS) rates for pNETs after surgical resection. Methods The demographics and clinicopathological information of T1-4N0-1M0 pNET patients between 2004 and 2018 were extracted from the Surveillance, Epidemiology and End Results database. X-tile software was used to determine the best cutoff value for the LNR. Patients were randomly divided into the training and the validation groups. A Cox regression model was used in the training group to obtain independent prognostic factors to develop nomograms for predicting OS and CSS. The concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to assess the nomograms. Patients were divided into four groups according to the model scores, and their survival curves were generated by the Kaplan–Meier method. Results A total of 806 patients were included in this study. The best cutoff value for the LNR was 0.16. The LNR was negatively correlated with both OS and CSS. Age, sex, marital status, primary site, grade, the LNR and radiotherapy were used to construct OS and CSS nomograms. In the training group, the C-index was 0.771 for OS and 0.778 for CSS. In the validation group, the C-index was 0.737 for OS and 0.727 for CSS. The calibration curves and AUC also indicated their good predictability. DCA demonstrated that the nomograms displayed better performance than the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition). Risk stratification indicated that patients with higher risk had a worse prognosis. Conclusions The LNR is an independent negative prognostic factor for pNETs. The nomograms we built can accurately predict long-term survival for pNETs after surgery.
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Affiliation(s)
- Jingxiang Shi
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, The Third Central Hospital of Tianjin, Tianjin, China.,Artificial Cell Engineering Technology Research Center, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China
| | - Sifan Liu
- School of Statistics, Tianjin University of Finance and Economics, Tianjin, China
| | - Jisen Cao
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, The Third Central Hospital of Tianjin, Tianjin, China.,Artificial Cell Engineering Technology Research Center, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China
| | - Shigang Shan
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, The Third Central Hospital of Tianjin, Tianjin, China.,Artificial Cell Engineering Technology Research Center, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China
| | - Chaoyi Ren
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, The Third Central Hospital of Tianjin, Tianjin, China.,Artificial Cell Engineering Technology Research Center, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China
| | - Jinjuan Zhang
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, The Third Central Hospital of Tianjin, Tianjin, China.,Artificial Cell Engineering Technology Research Center, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China
| | - Yijun Wang
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, The Third Central Hospital of Tianjin, Tianjin, China.,Artificial Cell Engineering Technology Research Center, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China
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23
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[Surgery of pancreatic neuroendocrine neoplasms: state of the art]. Chirurg 2022; 93:745-750. [PMID: 35499762 DOI: 10.1007/s00104-022-01641-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2022] [Indexed: 10/18/2022]
Abstract
Pancreatic neuroendocrine neoplasms (pNEN) have a rising incidence and are increasingly diagnosed at early and thus potentially resectable stages. Due to the rarity of these neoplasms the recommendations of currently available guidelines are mainly based on retrospective data. Surgical and oncological treatment of these rare diseases should only be performed at specialized centers. In cases of resectability without indications of diffuse metastases, complete resection with curative intent should be the treatment of choice. For small nonfunctional pNENs < 2 cm watch and wait strategies are recommended as an alternative to surgical treatment. Recent data, however, also showed an increased survival even of small (1-2 cm) pNENs after resection. For benign insulinomas and small nonfunctional well-differentiated pNENs parenchyma-sparing procedures, such as enucleation and segmental resection are available. The question of the influence of lymph node metastases on long-term disease-free survival and overall survival and consequently the role of systematic lymphadenectomy is still a matter of debate. In pNENs > 2 cm formal resection with lymphadenectomy is considered the gold standard. Minimally invasive and robotic-assisted procedures are of increasing importance also for formal pancreatic resection.
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24
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Comparative outcomes of pancreatic neuroendocrine neoplasms: A population-based analysis of the SEER database. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2181-2187. [DOI: 10.1016/j.ejso.2022.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/07/2022] [Accepted: 05/17/2022] [Indexed: 11/18/2022]
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25
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Liu C, Bian Y, Meng Y, Liu F, Cao K, Zhang H, Fang X, Li J, Yu J, Feng X, Ma C, Lu J, Xu J, Shao C. Preoperative Prediction of G1 and G2/3 Grades in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors Using Multimodality Imaging. Acad Radiol 2022; 29:e49-e60. [PMID: 34175209 DOI: 10.1016/j.acra.2021.05.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/05/2021] [Accepted: 05/13/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVES We aimed to develop and validate a multimodality radiomics model for the preoperative prediction of nonfunctional pancreatic neuroendocrine tumor (NF-pNET) grade (G). METHODS This retrospective study assessed 123 patients with surgically resected, pathologically confirmed NF-pNETs who underwent multidetector computed tomography and MRI scans between December 2012 and May 2020. Radiomic features were extracted from multidetector computed tomography and MRI. Wilcoxon rank-sum test and Max-Relevance and Min-Redundancy tests were used to select the features. The linear discriminative analysis (LDA) was used to construct the four models including a clinical model, MRI radiomics model, computed tomography radiomics model, and mixed radiomics model. The performance of the models was assessed using a training cohort (82 patients) and a validation cohort (41 patients), and decision curve analysis was applied for clinical use. RESULTS We successfully constructed 4 models to predict the tumor grade of NF- pNETs. Model 4 combined 6 features of T2-weighted imaging radiomics features and 1 arterial-phase computed tomography radiomics feature, and showed better discrimination in the training cohort (AUC = 0.92) and validation cohort (AUC = 0.85) relative to the other models. In the decision curves, if the threshold probability was 0.07-0.87, the use of the radiomics score to distinguish NF-pNET G1 and G2/3 offered more benefit than did the use of a "treat all patients" or a "treat none" scheme in the training cohort of the MRI radiomics model. CONCLUSION The LDA classifier combining multimodality images may be a valuable noninvasive tool for distinguishing NF-pNET grades and avoid unnecessary surgery.
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Garg R, Mohammed A, Singh A, Harnegie MP, Rustagi T, Stevens T, Chahal P. EUS-guided radiofrequency and ethanol ablation for pancreatic neuroendocrine tumors: A systematic review and meta-analysis. Endosc Ultrasound 2022; 11:170-185. [PMID: 35313416 PMCID: PMC9258014 DOI: 10.4103/eus-d-21-00044] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
EUS-guided radiofrequency ablation (RFA) and ethanol ablation (EA) for pancreatic neuroendocrine tumors (PNETs) have recently been reported with good outcomes. We performed a systematic review and meta-analysis to evaluate the comparative effectiveness and safety of EUS-RFA and EUS-EA in the treatment of PNETs. A comprehensive search of multiple databases (through October 2020) was performed to identify studies that reported outcomes of EUS-RFA and EUS-EA of PNETs. Outcomes assessed included clinical success, technical success, and adverse events (AEs). A total of 181 (100 EUS-RFA, 81 EUS-EA) patients (60.7 ± 9.2 years) with 204 (113 EUS-RFA, 91 EUS-EA) PNETs (mean size 15.1 ± 4.7 mm) were included from 20 studies. There was no significant difference in the rates of technical success (94.4% [95% confidence interval (CI): 88.5–97.3, I2 = 0] vs. 96.7% [95% CI: 90.8–98.8, I2 = 0]; P = 0.42), clinical success (85.2% (95% CI: 75.9–91.4, I2 = 0) vs. 82.2% [95% CI: 68.2–90.8, I2 = 10.1]; P = 0.65), and AEs (14.1% [95% CI: 7.1–26.3, I2 = 0] vs. 11.5% [95% CI: 4.7–25.4, I2 = 63.5]; P = 0.7) between EUS-RFA and EUS-EA, respectively. The most common AE was pancreatitis with the rate of 7.8% and 7.6% (P = 0.95) for EUS-RFA and EUS-EA, respectively. On meta-regression, the location of PNETs in head/neck of pancreas (P = 0.03) was a positive predictor of clinical success for EUS-RFA. EUS-RFA and EUS-EA have similar effectiveness and safety for PNETs ablation. Head/neck location of PNETs was a positive predictor for clinical success after EUS-RFA.
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Affiliation(s)
- Rajat Garg
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
| | - Abdul Mohammed
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
| | - Amandeep Singh
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
| | - Mary P Harnegie
- Cleveland Clinic Alumni Library, Cleveland Clinic, Cleveland, Ohio, USA
| | - Tarun Rustagi
- Department of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, New Mexico, USA
| | - Tyler Stevens
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
| | - Prabhleen Chahal
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
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27
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Kaslow SR, Vitiello GA, Prendergast K, Hani L, Cohen SM, Wolfgang C, Berman RS, Lee AY, Correa-Gallego C. Surgical Treatment of Patients with Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: An NCDB Analysis. Ann Surg Oncol 2022; 29:3522-3531. [PMID: 35246811 DOI: 10.1245/s10434-022-11477-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/08/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND Consensus guidelines discourage resection of poorly differentiated pancreatic neuroendocrine carcinoma (panNEC) given its association with poor long-term survival. This study assessed treatment patterns and outcomes for this rare malignancy using the National Cancer Database (NCDB). METHODS Patients with non-functional pancreatic neuroendocrine tumors in the NCDB (2004-2016) were categorized based on pathologic differentiation. Logistic and Cox proportional hazard regressions identified associations with resection and overall survival (OS). Survival was compared using Kaplan-Meier and log-rank tests. RESULTS Most patients (83%) in the cohort of 8560 patients had well-differentiated tumors (panNET). The median OS was 47 months (panNET, 63 months vs panNEC, 17 months; p < 0.001). Surgery was less likely for older patients (odds ratio [OR], 0.97), patients with panNEC (OR, 0.27), and patients with metastasis at diagnosis (OR, 0.08) (all p < 0.001). After propensity score-matching of these factors, surgical resection was associated with longer OS (82 vs 29 months; p < 0.001) and a decreased hazard of mortality (hazard ratio [HR], 0.37; p < 0.001). Surgery remained associated with longer OS when stratified by differentiation (98 vs 41 months for patients with panNET and 36 vs 8 months for patients with panNEC). Overall survival did not differ between patients with panNEC who underwent surgery and patients with panNET who did not (both 39 months; p = 0.294). CONCLUSIONS Poorly differentiated panNEC exhibits poorer survival than well-differentiated panNET. In the current cohort, surgical resection was strongly and independently associated with improved OS, suggesting that patients with panNEC who are suitable operative candidates should be considered for multimodality therapy, including surgery.
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Affiliation(s)
- Sarah R Kaslow
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Gerardo A Vitiello
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Katherine Prendergast
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Leena Hani
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Steven M Cohen
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Christopher Wolfgang
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Russell S Berman
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Ann Y Lee
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Camilo Correa-Gallego
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA.
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Matsunaga Y, Shiihara M, Takayama Y, Tahara J, Shimizu K, Tokushige K, Yamamoto M. Evaluation of the Significance of Lymphatic, Microvascular and Perineural Invasion in Patients With Pancreatic Neuroendocrine Neoplasms. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:150-159. [PMID: 35399168 PMCID: PMC8962817 DOI: 10.21873/cdp.10089] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/21/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Some prognostic factors for pancreatic neuroendocrine neoplasms (PanNENs) have been reported; however, the significance of lymphatic, microvascular, and perineural invasion remains unclear. We aimed to clarify the role of these factors in PanNEN recurrence. PATIENTS AND METHODS We analyzed 138 patients who underwent curative pancreatectomy and were pathologically diagnosed with PanNEN. We evaluated the association between clinicopathological factors and the recurrence of PanNENs. RESULTS The numbers of patients with lymphatic, microvascular, and perineural invasion were 34 (25%), 43 (31%) and 17 (12%), respectively. Twenty-four patients (17%) had recurrences, and the 3, 5, and 10-year recurrence-free survival (RFS) rates were 88%, 84%, and 76%, respectively. The recurrence sites (with duplication) were mainly the liver (twenty-two patients), followed by the lymph nodes (seven patients), and bone (two patients). In multivariate analyses, grade 2-3 and the presence of microvascular invasion were significant risk factors for RFS (hazard ratio=7.5 and 7.9, respectively). When examining outcomes according to these factors, the 5-year RFS rates of patients with risk scores of 0, 1, and 2 were 100%, 91%, and 32%, respectively (p<0.001). Even in patients with grade 1 (n=97) or limited resection (enucleation, splenic-preserving distal pancreatectomy, central pancreatectomy, and duodenum-preserving pancreatic head resection, n=62), the presence of microvascular invasion was a significant risk factor for RFS (hazard ratio=13.4 and 18.0, respectively). CONCLUSION The presence of microvascular invasion is an independent risk factor for recurrence in patients with PanNEN.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yutaro Matsunaga
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yukiko Takayama
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Junko Tahara
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kyoko Shimizu
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Katsutoshi Tokushige
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
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Krogh S, Grønbæk H, Knudsen AR, Kissmeyer-Nielsen P, Hummelshøj NE, Dam G. Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients. Front Endocrinol (Lausanne) 2022; 13:925632. [PMID: 35837305 PMCID: PMC9273749 DOI: 10.3389/fendo.2022.925632] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/24/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION The European Neuroendocrine Tumor Society, ENETS, reports variables of prognostic significance in pancreatic neuroendocrine tumors (PNET). However, studies have short follow-ups, and the optimal treatment remains controversial. We aimed to determine overall survival (OS), progression-free survival (PFS) after conservative treatment, and recurrence-free survival (RFS) after surgery and further to find predictors of aggressive PNET behavior to support treatment decisions. METHODS 174 patients with PNET treated at Aarhus University Hospital from 2011 to 2021 were included in a retrospective cohort study. Patients were divided into surgically resected (SUR, n=91) and medically or conservatively treated (MED, n=83). Variables were tested in univariate and multivariate survival analysis. Median follow-up time was 3.4 years in the MED group and 4.5 years in the SUR group. RESULTS The 5-year OS was 95% and 65% for the SUR and MED groups, respectively. The 5-year RFS in the SUR group was 80% whereas the 5-year PFS in the MED group was 41%. Larger tumor size, Ki67 index, tumor grade, and stage were predictive of shorter OS, RFS, and PFS. Further, chromogranin A was a predictor of OS. Larger tumor size was associated with higher stage and grade. Only 1 of 28 patients with stage 1 disease and size ≤2 cm developed progression on a watch-and-wait strategy during a median follow-up of 36 months. CONCLUSION This study supported the ENETS staging and grading system to be useful to predict OS, PFS, and RFS in PNET. Further, our data support that small, localized, low-grade PNETS can be followed with active surveillance.
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Affiliation(s)
- Sara Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | | | | | - Gitte Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- *Correspondence: Gitte Dam,
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30
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Shi H, Chen H, Qian B, Huang Z, Tan P, Peng Y, Tang X, Ye M. The 100 most cited articles on pancreatic neuroendocrine tumors from 2000 to 2020: a bibliometric analysis. Jpn J Clin Oncol 2021; 52:251-259. [PMID: 34954797 DOI: 10.1093/jjco/hyab205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 12/04/2021] [Indexed: 02/05/2023] Open
Abstract
PURPOSE The present study attempted to identify 100 most cited articles on pancreatic neuroendocrine tumors and characterize them via bibliometric analysis whereby it would provide an insight into the progress and trend in this field. METHODS Records regarding pancreatic neuroendocrine tumors and published between 2000 and 2020 were retrieved in 2021 through the Web of Science to identify the 100 most cited articles. RESULTS The 100 articles were screened in 17 434 records. The number of citations of the top-cited articles ranged from 151 to 1867. These articles were published in 47 journals among which the Journal of Clinical Oncology produced the most articles (n = 10). The USA contributed most of the articles (n = 44). Articles enrolled came from 58 institutions; the University of California System of the USA came to the top (n = 7). More than half of the articles were clinical studies (n = 55), basic science research reports accounting for a quarter. In clinical topics (n = 73), treatment issues were the most concerned (n = 21), in which more articles focused on targeted inhibitors. Articles about gene mutation were cited most frequently in basic science topics (n = 27). CONCLUSIONS This bibliometric analysis reflected the brief the progress and highlighted current trend in pancreatic neuroendocrine tumor research, providing references for further study.
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Affiliation(s)
- Hao Shi
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hao Chen
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Baolin Qian
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Zhiwei Huang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Peng Tan
- Sichuan Provincial Academician (Expert) Workstation, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yan Peng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiaowei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Mingxin Ye
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Shaib WL, Zakka K, Penley M, Jiang R, Akce M, Wu C, Maithel SK, Sarmiento JM, Kooby D, Behera M, Alese OB, El-Rayes BF. Role of Resection of the Primary in Metastatic Well-Differentiated Neuroendocrine Tumors. Pancreas 2021; 50:1382-1391. [PMID: 35041337 PMCID: PMC10848811 DOI: 10.1097/mpa.0000000000001936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Resection of the primary (RP) in metastatic neuroendocrine tumor (NET) is controversial. The aim was to evaluate survival outcomes for RP in metastatic NET patients. METHODS Data were obtained from US hospitals at the National Cancer Database between 2004 and 2014. χ2, analysis of variance tests, univariate, and multivariate cox proportional hazards models were evaluated. Kaplan-Meier curves and log-rank tests conducted to compare the survival difference of patient characteristics. RESULTS A total of 2361 patients were identified. The mean age was 62.1 years (standard deviation, 13 years), male-to-female ratio 1:1; 33% were small intestine, 26.3% pancreas, and 24.4% lung; 69.6% were well-differentiated; and 42.5% underwent RP. The 5-year overall survival (OS) was significantly improved for patients who underwent RP in small intestine (5-year OS, 63.9% vs 44.2%), lung (5-year OS, 65.4% vs 20.2%), and pancreas tumors (5-year OS, 75.6% vs 30.6%). On multivariate analysis, RP (hazard ratio, 0.46; 95% confidence interval, 0.29-0.73; P < 0.001), female, year of diagnosis 2010-2014, margin, Charlson-Deyo score less than 2, and age less than 51 years, were associated with better OS. CONCLUSIONS Resection of the primary in metastatic well-differentiated NET is associated with improved OS compared with no RP.
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Affiliation(s)
- Walid L. Shaib
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Katerina Zakka
- Department of Internal Medicine, Wellstar Atlanta Medical Center, Atlanta, GA
| | - McKenna Penley
- Winship Research Informatics, Emory University, Atlanta, GA
| | - Renjian Jiang
- Winship Research Informatics, Emory University, Atlanta, GA
| | - Mehmet Akce
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Christina Wu
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Shishir K. Maithel
- Department of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | | | - David Kooby
- Department of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Madhusmita Behera
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
- Winship Research Informatics, Emory University, Atlanta, GA
| | - Olatunji B. Alese
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Bassel F. El-Rayes
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
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Du B, Wang X, Zhang W, Tan Q, Wei Y, Shao Z. Management and outcomes of patients for non-functioning pancreatic neuroendocrine tumours: a multi-institutional analysis. ANZ J Surg 2021; 92:787-793. [PMID: 34723424 DOI: 10.1111/ans.17326] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/06/2021] [Accepted: 10/16/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND To analysed the short- and long-term outcomes of patients who underwent surgical resection for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) to gain insights into treatment approaches for this rare and heterogeneous entity. METHODS All patients who underwent surgical resection for NF-PNETs at The Second Affiliated Hospital of Guangzhou Medical University, and West China Hospital, Sichuan University, from 2009 to 2019 were retrospectively reviewed. The data of patients was including perioperative management, pathologic analysis and follow-up. RESULTS A total of 119 cases with histologically or cytologically confirmed NF-PNETs, The mean age of the patients was 52, and 56.3% were female. Twenty-three patients received post-operative adjuvant therapy, and five of nine (55.6%) patients with distant metastasis showed recurrence 14(60.9%) G2/G3 patients without distant metastasis received post-operative therapy with octreotide. Of these 14 patients, 3 (21.4%) revealed recurrence. Univariate analysis indicated that symptoms (P = 0.03), tumour size >4 cm (P = 0.029), ENETS stages III-IV (P < 0.001), positive lymph nodes (P < 0.001), vascular/perineural invasion (P < 0.001), and pathology grade G2 were associated with significantly higher risks of recurrence; age, gender, surgery type, and tumour location were not. Multivariate analysis revealed that positive lymph nodes (P < 0.001), vascular/peripheral invasion (P < 0.001), and pathology grade G3 (P = 0.03) are significant prognostic factors of tumour recurrence. CONCLUSION Positive lymph nodes, vascular/peripheral invasion and pathology grade G3 were related to recurrence of NF-PNETs. Lymph node resection is recommend when FNA biopsy indicates pathology grade G3 for patients with NF-PNETs.
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Affiliation(s)
- Bingqing Du
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xing Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Wangfa Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qingquan Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yisheng Wei
- Department of Gastrointestinal Surgery, Lab of Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zili Shao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Patterns and predictors of pancreatic neuroendocrine tumor prognosis: Are no two leaves alike? Crit Rev Oncol Hematol 2021; 167:103493. [PMID: 34653597 DOI: 10.1016/j.critrevonc.2021.103493] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 02/20/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous; thus, individual prognostic prediction is important. Clinicopathological features, like TNM stage, grade, and differentiation, are independent clinical predictors. However, single predictors are insufficient, as patients sharing similar clinicopathological features usually show distinct prognoses. Accordingly, novel nomograms and risk stratifications have been developed for more accurate PanNET prognostic prediction. Moreover, the exploration of molecular mechanisms has identified novel prognostic predictors for PanNET. Multi-analyte assays of molecular biomarkers provide a deeper understanding of PanNET features; however, the priority, and the optimal combination of classic and novel predictors for PanNET prognosis prediction remain unclear. In this review, we summarized the patterns and predictors of PanNET prognosis and discussed their clinical utility; we emphasized that PanNET at different stages have different superior predictor, and that multi-analyte assays are more sensitive than mono-analyte biomarkers. Therefore, combined biomarkers improve the accuracy of surveillance and optimize decision-making in clinical practice.
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Abstract
Surgical management of pancreatic neuroendocrine tumors (PNETS) is steadily evolving and is influenced by multiple factors. Sporadic PNETs are generally managed more aggressively than those occurring in the background of hereditary syndromes, and functioning PNETs are almost always resected if they are not metastatic. Localized nonfunctioning PNETs less than 2 cm can often be observed. Surgical resection for localized PNET greater than 2 cm comprises parenchymal sparing pancreas resections, such as enucleations, or formal anatomic resection, such as distal pancreatectomy or pancreaticoduodenectomy. PNETs commonly metastasize to the liver, and several systemic and liver-directed options to treat hepatic metastases are available.
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Lindner K, Binte D, Hoeppner J, Wellner UF, Schulte DM, Schmid SM, Luley K, Buchmann I, Tharun L, Keck T, Gebauer J, Kulemann B. Resection of Non-Functional Pancreatic Neuroendocrine Neoplasms-A Single-Center Retrospective Outcome Analysis. ACTA ACUST UNITED AC 2021; 28:3071-3080. [PMID: 34436034 PMCID: PMC8395435 DOI: 10.3390/curroncol28040268] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 08/07/2021] [Accepted: 08/08/2021] [Indexed: 01/08/2023]
Abstract
Surgery remains the only curative treatment of pancreatic neuroendocrine neoplasms (pNEN). Here, we report the outcome after surgery for non-functional pNEN at a European Neuroendocrine Tumor Society (ENETS) center in Germany between 2000 and 2019; cases were analyzed for surgical (Clavien–Dindo classification; CDc) and oncological outcomes. Forty-nine patients (tumor grading G1 n = 25, G2 n = 22, G3 n = 2), with a median age of 56 years, were included. Severe complications (CDc ≥ grade 3b) occurred in 11 patients (22.4%) and type B/C pancreatic fistulas (POPFs) occurred in 5 patients (10.2%); in-hospital mortality was 2% (n = 1). Six of seven patients with tumor recurrence (14.3%) had G2 tumors in the pancreatic body/tail. The median survival was 5.7 years (68 months; [1–228 months]). Neither the occurrence (p = 0.683) nor the severity of complications had an influence on the relapse behavior (p = 0.086). This also applied for a POPF (≥B, p = 0.609). G2 pNEN patients (n = 22) with and without tumor recurrence had similar median tumor sizes (4 cm and 3.9 cm, respectively). Five of the six relapsed G2 patients (83.3%) had tumor-positive lymph nodes (N+); all G2 pNEN patients with recurrence had initially been treated with distal pancreatic resection. Pancreatic resections for pNEN are safe but associated with relevant postoperative morbidity. Future studies are needed to evaluate suitable resection strategies for G2 pNEN.
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Affiliation(s)
- Kirsten Lindner
- Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (K.L.); (D.B.); (J.H.); (U.F.W.); (T.K.)
| | - Daniel Binte
- Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (K.L.); (D.B.); (J.H.); (U.F.W.); (T.K.)
| | - Jens Hoeppner
- Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (K.L.); (D.B.); (J.H.); (U.F.W.); (T.K.)
| | - Ulrich F. Wellner
- Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (K.L.); (D.B.); (J.H.); (U.F.W.); (T.K.)
| | - Dominik M. Schulte
- Division of Endocrinology, Diabetology and Clinical Nutrition, Department of Internal Medicine I, University Medical Center Schleswig-Holstein-Campus Kiel, 23538 Lübeck, Germany;
| | - Sebastian M. Schmid
- Institute for Endocrinology and Diabetes, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (S.M.S.); (J.G.)
| | - Kim Luley
- Clinic for Hematology and Oncology, University Hospital Schleswig-Holstein-Campus Lübeck, 23538 Lübeck, Germany;
| | - Inga Buchmann
- Department of Radiology and Nuclear Medicine, University of Lübeck, Ratzeburger Alle 160, 23538 Lübeck, Germany;
| | - Lars Tharun
- Institute of Pathology, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany;
| | - Tobias Keck
- Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (K.L.); (D.B.); (J.H.); (U.F.W.); (T.K.)
| | - Judith Gebauer
- Institute for Endocrinology and Diabetes, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (S.M.S.); (J.G.)
| | - Birte Kulemann
- Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; (K.L.); (D.B.); (J.H.); (U.F.W.); (T.K.)
- Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
- Correspondence:
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Han X, Yang J, Luo J, Chen P, Zhang Z, Alu A, Xiao Y, Ma X. Application of CT-Based Radiomics in Discriminating Pancreatic Cystadenomas From Pancreatic Neuroendocrine Tumors Using Machine Learning Methods. Front Oncol 2021; 11:606677. [PMID: 34367940 PMCID: PMC8339967 DOI: 10.3389/fonc.2021.606677] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 07/05/2021] [Indexed: 02/05/2023] Open
Abstract
Objectives The purpose of this study aimed at investigating the reliability of radiomics features extracted from contrast-enhanced CT in differentiating pancreatic cystadenomas from pancreatic neuroendocrine tumors (PNETs) using machine-learning methods. Methods In this study, a total number of 120 patients, including 66 pancreatic cystadenomas patients and 54 PNETs patients were enrolled. Forty-eight radiomic features were extracted from contrast-enhanced CT images using LIFEx software. Five feature selection methods were adopted to determine the appropriate features for classifiers. Then, nine machine learning classifiers were employed to build predictive models. The performance of the forty-five models was evaluated with area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score in the testing group. Results The predictive models exhibited reliable ability of differentiating pancreatic cystadenomas from PNETs when combined with suitable selection methods. A combination of DC as the selection method and RF as the classifier, as well as Xgboost+RF, demonstrated the best discriminative ability, with the highest AUC of 0.997 in the testing group. Conclusions Radiomics-based machine learning methods might be a noninvasive tool to assist in differentiating pancreatic cystadenomas and PNETs.
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Affiliation(s)
- Xuejiao Han
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jing Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Melanoma and Sarcoma Medical Oncology Unit, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jingwen Luo
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Pengan Chen
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Zilong Zhang
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Aqu Alu
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yinan Xiao
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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37
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Ha S, Song KB, Hong S, Shin D, Park Y, Kwon J, Lee W, Jun E, Lee JH, Hwang DW, Kim SC. The clinicopathologic and operative characteristics of patients with small nonfunctioning pancreatic neuroendocrine tumors. ANZ J Surg 2021; 91:E484-E492. [PMID: 34291544 DOI: 10.1111/ans.17055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 06/13/2021] [Accepted: 06/17/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND Incidentally detected, small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed on imaging modalities. This retrospective investigation evaluated the clinicopathologic characteristics and perioperative and oncologic outcomes in patients with small NF-PNETs undergoing curative resection. METHODS The medical records of 444 patients who underwent pancreatic resection for NF-PNETs at a single, large-volume institution between January 2000 and December 2018 were retrospectively reviewed. Patients were divided into those with small (≤2 cm) and large (>2 cm) tumors based on the largest tumor diameter on preoperative computed tomography (CT). Outcomes were also evaluated in subgroups of patients with small NF-PNET who did and did not undergo lymphadenectomy. RESULTS Of the 444 patients with NF-PNETs, 195 (43.9%) had small (≤2 cm) and 249 (56.1%) had large (>2 cm) NF-PNETs. The rate of parenchyma-preserving surgery (14.4% vs. 7.2%, p = 0.014) and the ratio of spleen preservation for left-sided pancreatectomy (65.6% vs. 38.3%, p < 0.001) were higher in the small NF-PNET group. Size on CT >2 cm (p < 0.001, hazard ratio [HR]: 5.836, 95% confidence interval [CI]: 2.474-13.769), presence of perineural invasion (p < 0.001, HR: 3.025, 95% CI: 1.640-5.577), World Health Organization (WHO) Grade 2 (p = 0.007, HR: 2.861, 95% CI: 1.325-6.176), and WHO Grade 3 (p < 0.001, HR: 11.537, 95% CI: 5.282-25.199) were independent predictors of disease-free survival (DFS). DFS did not differ significantly in patients with small NF-PNETs who did and did not undergo lymphadenectomy (p = 0.886). CONCLUSIONS Assessment of long-term oncologic outcomes suggests that surgical resection may cure small NF-PNETs. Minimally invasive surgery and organ-preserving surgery are acceptable treatment options for select patients with small NF-PNETs. The effect on survival outcomes of lymph node dissection for small NF-PNETs remains unclear.
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Affiliation(s)
- SuHyeon Ha
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Dakyum Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Jaewoo Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
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Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms. J Clin Med 2021; 10:jcm10122638. [PMID: 34203922 PMCID: PMC8232656 DOI: 10.3390/jcm10122638] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/28/2021] [Accepted: 06/07/2021] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.
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39
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Metastatic well-differentiated pancreatic neuroendocrine tumors to the liver: a narrative review of systemic and surgical management. JOURNAL OF PANCREATOLOGY 2021. [DOI: 10.1097/jp9.0000000000000068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
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40
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Calissendorff J, Bjellerup-Calissendorff F, Bränström R, Juhlin CC, Falhammar H. Characteristics, Treatment, Outcomes, and Survival in Neuroendocrine G1 and G2 Pancreatic Tumors: Experiences From a Single Tertiary Referral Center. Front Endocrinol (Lausanne) 2021; 12:657698. [PMID: 33927695 PMCID: PMC8076901 DOI: 10.3389/fendo.2021.657698] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 03/22/2021] [Indexed: 12/30/2022] Open
Abstract
Purpose Neuroendocrine tumors of the pancreas (Pan-NETs) are usually hormonally inactive with a capacity to metastasize. Since Pan-NETs are rare, more knowledge is needed. Methods We reviewed all patients' medical files with Pan-NET treated at a tertiary center (2006-2019). Grade 1 (G1) and grade 2 (G2) tumors were compared. The latter group was subdivided arbitrarily based on proliferation index into G2a (3-9.9%) and G2b (10-19.9%). Results We found 137 patients (76 females, 61 males; G1 n=66, G2 n=42), the median age at diagnosis 61 years (interquartile range (IQR) 50-71), and tumor size 2 cm (1.3-5 cm). The initial surgery was performed in 101 patients. The remaining (n=36) were followed conservatively. Metastatic disease was evident in 22 patients (16%) at diagnosis while new lesions developed in 13 out of 22 patients (59%). In patients without previous metastatic disease, progressive disease was discovered in 29% of G1 vs. 55% of G2 patients (P=0.009), 47% of G2a vs. 75% of G2b patients (NS). Survival was poorer in patients with metastasis at diagnosis vs. those with local disease (P<0.001). During follow-up of 74 months, Pan-NET related death was found in 10 patients. Survival was not different between G1 vs. G2 or G2a vs. G2b, or if tumors were functional. Size ≤2 cm was associated with a better outcome (P=0.004). During the follow-up of small tumors (≤2 cm, n=36) two were resected. Conclusion In small non-functional Pan-NETs, active surveillance is reasonable. Progressive disease was more common in G2, but survival was similar in G1, G2 and between G2 subgroups. Survival was poorer in patients with metastasis at diagnosis.
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Affiliation(s)
- Jan Calissendorff
- Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Freja Bjellerup-Calissendorff
- Department of Pathology, Västmanland County Hospital, Västerås, Sweden
- Center for Clinical Research, Uppsala University, Västmanland County Hospital, Västerås, Sweden
| | - Robert Bränström
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Breast, Endocrine and Sarcoma Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - C. Christofer Juhlin
- Department of Clinical Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
| | - Henrik Falhammar
- Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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41
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Bezzi C, Mapelli P, Presotto L, Neri I, Scifo P, Savi A, Bettinardi V, Partelli S, Gianolli L, Falconi M, Picchio M. Radiomics in pancreatic neuroendocrine tumors: methodological issues and clinical significance. Eur J Nucl Med Mol Imaging 2021; 48:4002-4015. [PMID: 33835220 DOI: 10.1007/s00259-021-05338-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 03/24/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. METHODS Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. RESULTS Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7-0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. CONCLUSIONS Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients.
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Affiliation(s)
- C Bezzi
- Vita-Salute San Raffaele University, Via Olgettina 58, Milan, 20132, Italy
| | - P Mapelli
- Vita-Salute San Raffaele University, Via Olgettina 58, Milan, 20132, Italy.,Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - L Presotto
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - I Neri
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - P Scifo
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - A Savi
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - V Bettinardi
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - S Partelli
- Vita-Salute San Raffaele University, Via Olgettina 58, Milan, 20132, Italy.,Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
| | - L Gianolli
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - M Falconi
- Vita-Salute San Raffaele University, Via Olgettina 58, Milan, 20132, Italy.,Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
| | - M Picchio
- Vita-Salute San Raffaele University, Via Olgettina 58, Milan, 20132, Italy. .,Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
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Chan H, Zhang L, Choti MA, Kulke M, Yao JC, Nakakura EK, Bloomston M, Benson AB, Shah MH, Strosberg JR, Bergsland EK, Van Loon K. Recurrence Patterns After Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: Analysis From the National Comprehensive Cancer Network Oncology Outcomes Database. Pancreas 2021; 50:506-512. [PMID: 33939661 PMCID: PMC8097723 DOI: 10.1097/mpa.0000000000001791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed. METHODS Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis. Descriptive statistics and Kaplan-Meier estimates were used to calculate recurrence rates and time-associated end points, respectively. RESULTS Of 294 patients with GEPNETs, 50% were male, 88% were White, and 99% had Eastern Cooperative Oncology Group performance status 0 to 1. The median age was 55 years (range, 20-90). The median follow-up time from R0 resection was 62.1 months. Recurrence rates were 18% in small bowel NETs (n = 110), 26% in pancreatic NETs (n = 141), and 10% in colon/rectum NETs (n = 50). The frequency of surveillance imaging was highly variable. CONCLUSIONS R0 resection was associated with variable risk of recurrence across subtypes. Further research to inform refinement of guidelines for the appropriate duration of surveillance after R0 resection is needed.
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Affiliation(s)
- Hilary Chan
- From the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
| | - Li Zhang
- From the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
| | - Michael A Choti
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
| | | | - James C Yao
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eric K Nakakura
- From the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
| | - Mark Bloomston
- The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Al B Benson
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
| | - Manisha H Shah
- The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, OH
| | | | - Emily K Bergsland
- From the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
| | - Katherine Van Loon
- From the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
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Ricci C, Partelli S, Landoni L, Rinzivillo M, Ingaldi C, Andreasi V, Nessi C, Muffatti F, Fontana M, Tamburrino D, Deiro G, Alberici L, Campana D, Panzuto F, Bassi C, Falconi M, Casadei R. Sporadic non-functioning pancreatic neuroendocrine tumours: multicentre analysis. Br J Surg 2021; 108:811-816. [PMID: 33724300 DOI: 10.1093/bjs/znaa141] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/05/2020] [Accepted: 11/24/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Outcomes after surgery for sporadic pancreatic neuroendocrine neoplasms (Pan-NENs) were evaluated. METHODS This multicentre study included patients who underwent radical pancreatic resection for sporadic non-functioning Pan-NENs. In survival analysis, the risk of mortality in this cohort was analysed in relation to that of the matched healthy Italian population. Relative survival (RS) was calculated as the rate between observed and expected survival. Factors related to RS were investigated using multivariable modelling. RESULTS Among 964 patients who had pancreatic resection for sporadic non-functioning Pan-NENs, the overall RS rate was 91.8 (95 per cent c.i. 81.5 to 96.5) per cent. 2019 WHO grade (hazard ratio (HR) 5.75 (s.e. 4.63); P = 0.030) and European Neuroendocrine Tumour Society (ENETS) TNM stage (6.73 (3.61); P < 0.001) were independent predictors of RS. The probability of a normal lifespan for patients with G1, G2, G3 Pan-NENS, and pancreatic neuroendocrine carcinomas (Pan-NECs) was 96.7, 54.8, 0, and 0 per cent respectively. The probability of a normal lifespan was 99.8, 99.3, 79.8, and 46.8 per cent for those with stage I, II, III, and IV disease respectively. The overall disease-free RS rate was 73.6 (65.2 to 79.5) per cent. 2019 WHO grade (HR 2.10 (0.19); P < 0.001) and ENETS TNM stage (HR 2.50 (0.24); P < 0.001) significantly influenced disease-free RS. The probability of disease-free survival was 93.2, 84.9, 45.2, and 6.8 per cent for patients with stage I, II, III, and IV disease, and 91.9, 45.2, 9.4, and 0.7 per cent for those with G1, G2, G3 Pan-NENS, and Pan-NECs, respectively. CONCLUSION A surgical approach seems without benefit for Pan-NECs, and unnecessary for small G1 sporadic Pan-NENs. Surgery alone may be insufficient for stage III-IV and G3 Pan-NENs.
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Affiliation(s)
- C Ricci
- Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Internal Medicine and Surgery; Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - S Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy.,'Vita-Salute' San Raffaele University, Milan, Italy
| | - L Landoni
- General and Pancreatic Surgery Department, Pancreas Institute-University of Verona Hospital Trust, Verona, Italy
| | - M Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - C Ingaldi
- Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Internal Medicine and Surgery; Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - V Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy.,'Vita-Salute' San Raffaele University, Milan, Italy
| | - C Nessi
- General and Pancreatic Surgery Department, Pancreas Institute-University of Verona Hospital Trust, Verona, Italy
| | - F Muffatti
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy.,'Vita-Salute' San Raffaele University, Milan, Italy
| | - M Fontana
- General and Pancreatic Surgery Department, Pancreas Institute-University of Verona Hospital Trust, Verona, Italy
| | - D Tamburrino
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy
| | - G Deiro
- General and Pancreatic Surgery Department, Pancreas Institute-University of Verona Hospital Trust, Verona, Italy
| | - L Alberici
- Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Internal Medicine and Surgery; Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - D Campana
- Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Division of Oncology, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - F Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - C Bassi
- General and Pancreatic Surgery Department, Pancreas Institute-University of Verona Hospital Trust, Verona, Italy
| | - M Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy.,'Vita-Salute' San Raffaele University, Milan, Italy
| | - R Casadei
- Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Internal Medicine and Surgery; Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Kumar S, Raobiakady R, Watkins D, Terlizzo M, Bhogal RH. Radical resection of large metastatic non-functioning pancreatic neuroendocrine carcinoma complicated by splenic vein thrombosis and sinistral portal hypertension. Int J Surg Case Rep 2021; 81:105724. [PMID: 33820735 PMCID: PMC8073194 DOI: 10.1016/j.ijscr.2021.105724] [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: 02/16/2021] [Revised: 03/02/2021] [Accepted: 03/03/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE There are limited reports in the literature of radical surgical resection for pancreatic neuroendocrine carcinoma (PNEC). In patients with non-functioning PNEC (NF-PNEC) within the tail of the pancreas tumours can cause splenic vein thrombosis (SVT) and subsequent sinitral portal hypertension (SPH). Radical surgical resection in such patients with concomitant liver metastasis has not previously been reported. CASE PRESENTATION We present a 67-year old female patient who presented with a large NF-PNEC within the tail of the pancreas with liver metastasis. We performed a distal pancreatectomy, splenectomy, partial gastrectomy and liver resection to achieve radical resecton. DISCUSSION All patients with NF-PNEC within the tail of the pancreatic should be considered for radical surgical resection. In the presence of multi-visceral involvement and complications such as SVT and/or SPH multi-speciality surgical expertise is likely to be required. CONCLUSION Radical multi-visceral resection for large NF-PNEC can be safely performed in the presence of SVT and SPH.
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Affiliation(s)
- S Kumar
- The Royal Marsden Hospital (NHS Foundation Trust), Department of Surgery, Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom; Division of Radiotherapy & Imaging, The Institute for Cancer Research, 123 Old Brompton Road, London, United Kingdom; Imperial College London, Department of Surgery & Cancer, Exhibition Road, South Kensington, London, SW7 2BU, United Kingdom
| | - R Raobiakady
- The Royal Marsden Hospital (NHS Foundation Trust), Department of Anaesthetics, Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom
| | - D Watkins
- The Royal Marsden Hospital (NHS Foundation Trust), Department of Oncology, Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom
| | - M Terlizzo
- The Royal Marsden Hospital (NHS Foundation Trust), Department of Histopathology, Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom
| | - R H Bhogal
- The Royal Marsden Hospital (NHS Foundation Trust), Department of Surgery, Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom; Division of Radiotherapy & Imaging, The Institute for Cancer Research, 123 Old Brompton Road, London, United Kingdom.
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Klimov S, Xue Y, Gertych A, Graham RP, Jiang Y, Bhattarai S, Pandol SJ, Rakha EA, Reid MD, Aneja R. Predicting Metastasis Risk in Pancreatic Neuroendocrine Tumors Using Deep Learning Image Analysis. Front Oncol 2021; 10:593211. [PMID: 33718106 PMCID: PMC7946991 DOI: 10.3389/fonc.2020.593211] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/18/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The prognosis of patients with pancreatic neuroendocrine tumors (PanNET), the second most common type of pancreatic cancer, varies significantly, and up to 15% of patients develop metastasis. Although certain morphological characteristics of PanNETs have been associated with patient outcome, there are no available morphology-based prognostic markers. Given that current clinical histopathology markers are unable to identify high-risk PanNET patients, the development of accurate prognostic biomarkers is needed. Here, we describe a novel machine learning, multiclassification pipeline to predict the risk of metastasis using morphological information from whole tissue slides. METHODS Digital images from surgically resected tissues from 89 PanNET patients were used. Pathologist-annotated regions were extracted to train a convolutional neural network (CNN) to identify tiles consisting of PanNET, stroma, normal pancreas parenchyma, and fat. Computationally annotated cancer or stroma tiles and patient metastasis status were used to train CNN to calculate a region based metastatic risk score. Aggregation of the metastatic probability scores across the slide was performed to predict the risk of metastasis. RESULTS The ability of CNN to discriminate different tissues was high (per-tile accuracy >95%; whole slide cancer regions Jaccard index = 79%). Cancer and stromal tiles with high evaluated probability provided F1 scores of 0.82 and 0.69, respectively, when we compared tissues from patients who developed metastasis and those who did not. The final model identified low-risk (n = 76) and high-risk (n = 13) patients, as well as predicted metastasis-free survival (hazard ratio: 4.71) after adjusting for common clinicopathological variables, especially in grade I/II patients. CONCLUSION Using slides from surgically resected PanNETs, our novel, multiclassification, deep learning pipeline was able to predict the risk of metastasis in PanNET patients. Our results suggest the presence of prognostic morphological patterns in PanNET tissues, and that these patterns may help guide clinical decision making.
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Affiliation(s)
- Sergey Klimov
- Department of Biology, Georgia State University, Atlanta, GA, United States
- Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, United States
| | - Yue Xue
- Department of Pathology, Northwestern University, Chicago, IL, United States
| | - Arkadiusz Gertych
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Faculty of Biomedical Engineering, Silesian University of Technology, Zabrze, Poland
| | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | - Yi Jiang
- Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, United States
| | - Shristi Bhattarai
- Department of Biology, Georgia State University, Atlanta, GA, United States
| | - Stephen J Pandol
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Emad A Rakha
- Department of Cellular Pathology, University of Nottingham, Nottingham, United Kingdom
| | - Michelle D Reid
- Department of Pathology, Emory University, Atlanta, GA, United States
| | - Ritu Aneja
- Department of Biology, Georgia State University, Atlanta, GA, United States
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Fusai GK, Tamburrino D, Partelli S, Lykoudis P, Pipan P, Di Salvo F, Beghdadi N, Dokmak S, Wiese D, Landoni L, Nessi C, Busch ORC, Napoli N, Jang JY, Kwon W, Del Chiaro M, Scandavini C, Abu-Awwad M, Armstrong T, Hilal MA, Allen PJ, Javed A, Kjellman M, Sauvanet A, Bartsch DK, Bassi C, van Dijkum EJMN, Besselink MG, Boggi U, Kim SW, He J, Wolfgang CL, Falconi M. Portal vein resection during pancreaticoduodenectomy for pancreatic neuroendocrine tumors. An international multicenter comparative study. Surgery 2021; 169:1093-1101. [PMID: 33357999 DOI: 10.1016/j.surg.2020.11.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/18/2020] [Accepted: 11/02/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. METHODS This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. RESULTS Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). CONCLUSION This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.
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Affiliation(s)
- Giuseppe K Fusai
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, London, United Kingdom
| | - Domenico Tamburrino
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital, Milan, Italy.
| | - Stefano Partelli
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital, Milan, Italy
| | - Panagis Lykoudis
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, London, United Kingdom
| | - Peter Pipan
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, London, United Kingdom
| | - Francesca Di Salvo
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital, Milan, Italy
| | - Nassiba Beghdadi
- Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif, Université de Paris-Paris Diderot, Beaujon Hospital, Clichy, France
| | - Safi Dokmak
- Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif, Université de Paris-Paris Diderot, Beaujon Hospital, Clichy, France
| | - Dominik Wiese
- Department of Visceral, Thoracic, and Vascular Surgery, Philipps University, Marburg, Germany
| | - Luca Landoni
- Unit of General and Pancreatic Surgery, University and Hospital Trust of Verona, Italy
| | - Chiara Nessi
- Unit of General and Pancreatic Surgery, University and Hospital Trust of Verona, Italy
| | - O R C Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Netherlands
| | - Niccolò Napoli
- Division of General and Transplant Surgery, University of Pisa, Italy
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, South Korea
| | - Wooil Kwon
- Department of Surgery, Seoul National University College of Medicine, South Korea
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO
| | - Chiara Scandavini
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Mahmoud Abu-Awwad
- Department of Surgery, University Hospital Southampton, United Kingdom
| | - Thomas Armstrong
- Department of Surgery, University Hospital Southampton, United Kingdom
| | - Mohamed Abu Hilal
- Department of Surgery, University Hospital Southampton, United Kingdom; Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy
| | - Peter J Allen
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Surgical Oncology, Duke University, Durham, NC
| | - Ammar Javed
- Division of Surgical Oncology, Surgical Oncology, Pathology and Oncology, Johns Hopkins Medical Institution, Baltimore, MD
| | - Magnus Kjellman
- Department of Molecular Medicine and Surgery, Division of Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Alain Sauvanet
- Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif, Université de Paris-Paris Diderot, Beaujon Hospital, Clichy, France
| | - Detlef K Bartsch
- Department of Visceral, Thoracic, and Vascular Surgery, Philipps University, Marburg, Germany
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, University and Hospital Trust of Verona, Italy
| | - E J M Nieveen van Dijkum
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Netherlands
| | - M G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Netherlands
| | - Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa, Italy
| | - Sun-Whe Kim
- Department of Surgery, Seoul National University College of Medicine, South Korea
| | - Jin He
- Division of Surgical Oncology, Surgical Oncology, Pathology and Oncology, Johns Hopkins Medical Institution, Baltimore, MD
| | - Christofer L Wolfgang
- Division of Surgical Oncology, Surgical Oncology, Pathology and Oncology, Johns Hopkins Medical Institution, Baltimore, MD
| | - Massimo Falconi
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital, Milan, Italy
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Muniraj T, Aslanian HR. Pancreatic Neuroendocrine Tumors. GERIATRIC GASTROENTEROLOGY 2021:1933-1951. [DOI: 10.1007/978-3-030-30192-7_81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Cuthbertson DJ, Barriuso J, Lamarca A, Manoharan P, Westwood T, Jaffa M, Fenwick SW, Nuttall C, Lalloo F, Prachalias A, Pizanias M, Wieshmann H, McNamara MG, Hubner R, Srirajaskanthan R, Vivian G, Ramage J, Weickert MO, Pritchard DM, Vinjamuri S, Valle J, Yip VS. The Impact of 68Gallium DOTA PET/CT in Managing Patients With Sporadic and Familial Pancreatic Neuroendocrine Tumours. Front Endocrinol (Lausanne) 2021; 12:654975. [PMID: 34163434 PMCID: PMC8215358 DOI: 10.3389/fendo.2021.654975] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 05/11/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of 68Gallium (68Ga)-DOTA PET/CT in managing patients with panNETs. DESIGN A retrospective study conducted across three tertiary UK NET referral centres. METHODS Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a 68Ga-DOTA PET/CT scan for a suspected panNET. RESULTS We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 vs. 9.3% (n=163 vs. 17) alive vs. dead (3 data missing), 141 sporadic vs. 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional vs. functional tumours comprised 73.2 vs. 21.3% (n=134 vs. 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224 68Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall, 68Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases. CONCLUSION 68Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease.
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Affiliation(s)
- Daniel J. Cuthbertson
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
- Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
- *Correspondence: Daniel J. Cuthbertson,
| | - Jorge Barriuso
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Angela Lamarca
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Prakash Manoharan
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust ENETS Centre of Excellence, Manchester, United Kingdom
| | - Thomas Westwood
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust ENETS Centre of Excellence, Manchester, United Kingdom
| | - Matthew Jaffa
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Stephen W. Fenwick
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Christina Nuttall
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Fiona Lalloo
- Department of Clinical Genetics, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary’s Hospital, Manchester, United Kingdom
| | - Andreas Prachalias
- Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Michail Pizanias
- Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Hulya Wieshmann
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Mairead G. McNamara
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Richard Hubner
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Raj Srirajaskanthan
- Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Gillian Vivian
- Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - John Ramage
- Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Martin O. Weickert
- The Arden Neuroendocrine Centre, ENETS Centre of Excellence, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
| | - D Mark Pritchard
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
- Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Sobhan Vinjamuri
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Juan Valle
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Vincent S. Yip
- Barts and the London HPB Centre, Royal London Hospital, London, United Kingdom
- Department of Pancreatobiliary Surgery, Royal Liverpool University Hospital, Liverpool, United Kingdom
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Sun Y, Wang Y, Li R, Kang G, Zhang M, Chen X, Jin M, Liu Y, He Y, Zhu X, Kang Q, Zhou F, Yu Q. Surgical resection of primary tumor is associated with prolonged survival in low-grade pancreatic neuroendocrine tumors. Clin Res Hepatol Gastroenterol 2021; 45:101432. [PMID: 32386797 DOI: 10.1016/j.clinre.2020.04.003] [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: 11/25/2019] [Revised: 04/02/2020] [Accepted: 04/09/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing over the past few decades. Surgery for low-grade and small PNETs of less than 2cm and N0M0 is still debated. The purpose of this study is to examine the association between surgical resection and survival in patients with low-grade nonfunctioning PNETs. MATERIALS AND METHODS Patients diagnosed with PNETs between 2004 and 2015 were extracted from SEER. Kaplan-Meier methods and Cox proportional hazard models were used to estimate independent predictors in PNETs patients. RESULTS A total of 2637 patients (2147 underwent surgical resection and 490 did not undergo surgery) with histologically confirmed low-grade PNETs in this cohort study. Overall survival (OS) and cancer-specific survival (CSS) of patients with surgery was better than those without surgery (log rank test POS<0.001, PCSS<0.001). Multivariate Cox regression analysis showed that surgical status was an independent prognostic factor associated with OS (HR 3.257, 95%CI: 2.635, 4.026) and CSS (HR 3.546, 95%CI: 2.798, 4.493). Subgroup analysis suggested the patients receiving surgery apparently had better OS and CSS regardless of tumor size (all log rank test POS<0.001, all log rank test PCSS<0.001) and SEER stage (all log rank test POS<0.001, all log rank test PCSS<0.001), compared to patients without removal of the primary tumor. CONCLUSIONS Surgical resection of primary tumor may have a significant benefit on survival for patients with low-grade nonfunctioning PNETs. To determine the optimal management, grade, stage and tumor size should be considered comprehensively.
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Affiliation(s)
- Yaoyao Sun
- Cancer System Biology Center, China-Japan Union Hospital, Jilin University, China; Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yueying Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Rixin Li
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Guojun Kang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Mingyuan Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Xin Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Mengdi Jin
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yang Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yang He
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Xiaojing Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Qi Kang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Fengfeng Zhou
- Cancer System Biology Center, China-Japan Union Hospital, Jilin University, China
| | - Qiong Yu
- Cancer System Biology Center, China-Japan Union Hospital, Jilin University, China; Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China.
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