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1
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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] [Download PDF] [Figures] [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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2
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Черных ТМ, Малюгин ДА, Хачатуров МВ, Шефер АА, Золоедов ВИ. [Current views on the treatment of insulinoma]. PROBLEMY ENDOKRINOLOGII 2024; 70:46-55. [PMID: 38433541 PMCID: PMC10926244 DOI: 10.14341/probl13281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 07/06/2023] [Accepted: 07/20/2023] [Indexed: 03/05/2024]
Abstract
RELEVANCE Insulinoma is the most common hormonally active neuroendocrine tumor (NET) of the pancreas. In recent years, there has been a trend towards an increase in the incidence of NET especially insulinoma. AIM Summarizing and analyzing current data on various approaches to the treatment of insulinoma. Our review includes a comprehensive assessment of the advantages and disadvantages of currently available insulinoma treatment methods in comparison with past experience, as well as a review of promising methods that are not currently widely used. MATERIALS AND METHODS Analysis of literature from such databases as scientific electronic library elibrary.ru, Pubmed, Google Scholar, MedLine, Scopus and Web of Science. RESULTS The most common treatment for insulinoma is surgery. For patients with high operative risk, alternative methods such as alcohol ablation, radiofrequency ablation, and tumor embolization may be used. Medications include the use of somatostatin analogues, diazoxide. The literature describes the potential benefit of the use of beta-blockers, phenytoin, glucagon, however, in clinical trials, these drugs have not demonstrated a significant effect. For the treatment of malignant and metastatically advanced insulinoma, targeted therapy (primarily Everolimus), chemotherapy, as well as embolization (including chemoembolization, radioembolization), radiofrequency ablation (RFA), microwave ablation and cryoablation, ultrasound ablation (HIFU), laser ablation, brachytherapy, irreversible electroporation are used. CONCLUSION The study of new drugs is an important task for scientists, among medications the most promising are new generations of somatostatin analogues, targeted drugs and chemotherapy drugs. The rare frequency of insulinoma makes it difficult to conduct randomized controlled trials and prospective studies. That is why physicians and scientists need to maintain close contacts with each other and take into account the experience of treating each patient with such disease, which will help develop effective treatment algorithms in the future.
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Affiliation(s)
- Т. М. Черных
- Воронежский государственный медицинский университет им. Н.Н. Бурденко
| | - Д. А. Малюгин
- Воронежский государственный медицинский университет им. Н.Н. Бурденко
| | - М. В. Хачатуров
- Первый московский государственный медицинский университет им. И.М. Сеченова
| | - А. А. Шефер
- Воронежский государственный медицинский университет им. Н.Н. Бурденко
| | - В. И. Золоедов
- Воронежский государственный медицинский университет им. Н.Н. Бурденко
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3
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Elkelany OO, Karaisz FG, Davies B, Krishna SG. An Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their Management. Curr Oncol 2023; 30:7566-7580. [PMID: 37623030 PMCID: PMC10453483 DOI: 10.3390/curroncol30080549] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology. This review aims to highlight key aspects of these topics, with a specific focus on emerging EUS-guided procedures for the management of PanNETs.
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Affiliation(s)
- Osama O. Elkelany
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Fred G. Karaisz
- Division of Gastroenterology, Hepatology and Nutrition, 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 43201, 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
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Choi JH, Paik WH, Lee SH, Lee MW, Cho IR, Ryu JK, Kim YT. Efficacy and predictive factors of endoscopic ultrasound-guided ethanol ablation in benign solid pancreatic tumors. Surg Endosc 2023:10.1007/s00464-022-09833-3. [PMID: 37079095 PMCID: PMC10338579 DOI: 10.1007/s00464-022-09833-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 12/16/2022] [Indexed: 04/21/2023]
Abstract
BACKGROUNDS AND OBJECTIVES Endoscopic ultrasound-guided ethanol ablation (EUS-EA) has recently been introduced for the management of solid pancreatic tumors, including pancreatic neuroendocrine tumors (PNETs) and solid pseudopapillary tumors (SPTs). The study aims to evaluate the efficacy and predictive factors for response of EUS-EA in solid pancreatic tumors. METHODS Between October 2015 and July 2021, 72 patients who underwent EUS-EA for solid pancreatic tumors were included. The study outcomes were to evaluate the efficacy of EUS-EA with complete remission (CR) and objective response, and their predictive factors. RESULTS During follow-up, 47 patients were diagnosed with PNETs and 25 with SPTs. Eight cases reached CR and 48 reached objective response. When compared with SPTs, PNETs showed similar duration to reach CR (median not reached; p = 0.319), but shorter duration to reach objective response (PNETs: median 20.6 months, 95%CI 10.26-30.88; SPTs: median 47.7 months, 95%CI 18.14-77.20; p = 0.018). Ethanol dosage > 0.35 ml/cm3 shortened the duration to reach CR (median not reached; p = 0.026) and objective response (median 42.5 months, 95%CI 25.34-59.66 vs. 19.6 months, 95%CI 10.17-29.09; p = 0.006). CR had no significant predictive factors, but PNETs showed significant predictive factors for objective response (HR 3.34, 95%CI 1.07-10.43; p = 0.038). Twenty-seven patients experienced adverse events, and there were two severe cases. CONCLUSION EUS-EA for pancreatic solid lesions seems feasible as a local treatment for patients who refuse or are unfit for surgery. Additionally, PNETs seem to be the better candidate for EUS-EA.
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Affiliation(s)
- Jin Ho Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Woo Hyun Paik
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Min Woo Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - In Rae Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ji Kon Ryu
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong-Tae Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
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Nabi Z, Lakhtakia S, Reddy DN. Current status of the role of endoscopy in evaluation and management of gastrointestinal and pancreatic neuroendocrine tumors. Indian J Gastroenterol 2023; 42:158-172. [PMID: 37129761 DOI: 10.1007/s12664-023-01362-8] [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: 03/07/2022] [Accepted: 02/15/2023] [Indexed: 05/03/2023]
Abstract
The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased over the last several decades. In general, NETs are slow-growing neoplasms and the data on the natural history is still evolving. The availability and improved utilization of advanced imaging modalities have allowed the selection of cases suitable for endotherapy. In this regard, endoscopic ultrasound (EUS) has emerged as a central imaging modality to assess the depth of infiltration in gastroduodenal as well as rectal NETs. Enhanced EUS modalities, including contrast-enhanced EUS and EUS elastography, reliably differentiate pancreatic neuroendocrine tumors (PNETs) from adenocarcinomas and may enable prediction of aggressive PNETs. With recent developments in therapeutic endoscopy, a large proportion of GEP-NETs can be safely managed endoscopically. Endoscopic resection techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), allow the safe removal of gastroduodenal and rectal NETs. Recent data indicate that modified EMR techniques may be superior to conventional EMR with regard to histologically complete resection. Device-assisted endoscopic full thickness resection is emerging as a safe and effective technique for upper gastrointestinal as well as rectal NETs. In selected cases with PNETs, who are otherwise unfit for surgery, EUS-guided ablation is increasingly being recognized as a safe treatment option. This review focusses on evidence-based approaches to endoscopic evaluation and the management of GEP-NETs with special emphasis on recent advancements.
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, Hyderabad, 500 082, India.
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Yan Z, Zhu C, Wu X, Zhu H, Yuan T, Luo Y, Feng Y, Wang Q, Zhang S, Xue H, Zheng Z, Yang A. A single-center experience on endoscopic ultrasonography-guided ethanol ablation of insulinomas. Pancreatology 2023; 23:98-104. [PMID: 36577553 DOI: 10.1016/j.pan.2022.12.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 11/20/2022] [Accepted: 12/12/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND/OBJECTIVES As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence. METHODS A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed. RESULTS The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment. CONCLUSIONS For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.
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Affiliation(s)
- Zhiyu Yan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China; Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China
| | - Cheng Zhu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xi Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Huijuan Zhu
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Tao Yuan
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yaping Luo
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yunlu Feng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Qiang Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Shengyu Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Zehui Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Aiming Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
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Management of Small Nonfunctioning Pancreatic Neuroendocrine Neoplasms: Current Opinion and Controversies. J Clin Med 2022; 12:jcm12010251. [PMID: 36615051 PMCID: PMC9821009 DOI: 10.3390/jcm12010251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022] Open
Abstract
The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has increased due to the widespread use of high-resolution diagnostic imaging in screening programs. Most PNENs are slow-growing indolent neoplasms. However, a local invasion or metastasis can sometimes occur with PNENs, leading to a poor prognosis. The management of small, nonfunctioning PNENs remains under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgery remains a high-risk operation with a 28-30% morbidity and 1% mortality. Therefore, the decision on how to manage small PNENs is challenging. This review focuses on the management of small nonfunctioning PNENs. We also highlight the malignant potential of small PNENs according to tumor size, tumor grade, and tumor biomarker. Endoscopic-ultrasound-guided biopsy is recommended to evaluate the potential risk of malignancy. Furthermore, we discuss the current guidelines and future directions for the management of small PNENs.
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S B, Carpenter A, Yadav SK, Agarwal V, Somashekhar U, Sharma D. Role of Endoscopic Ultrasound Ablative Therapy in Management of Pancreatic Neuroendocrine Tumors: a Systematic Review. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03625-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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9
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Matsumoto K, Kato H. Endoscopic ablation therapy for the pancreatic neoplasms. Dig Endosc 2022; 35:430-442. [PMID: 36366955 DOI: 10.1111/den.14468] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022]
Abstract
Recently, endoscopic ultrasound (EUS)-guided ablation therapy has been reported as a less invasive therapy for patients with pancreatic neoplasms. Some ablation techniques, including injective ablation (using ethanol or other ablative agents), radiofrequency ablation (RFA), photodynamic therapy, and laser ablation, have been described in the literature. Among these, injective ablation and RFA are more frequently used for treating pancreatic neoplasms. Few studies have evaluated the effectiveness of EUS-guided ethanol ablation (EUS-EA) for potentially malignant solid neoplasms (neuroendocrine neoplasms or solid pseudopapillary neoplasms) and have reported a complete response (CR) rate of 60-80%. In addition, the CR rate after EUS-RFA for these lesions has been reported to be 55-100%, with no additional procedure-related adverse events (AEs). Regarding the amelioration of the symptoms of an insulinoma, the success rates of both the therapies were found to be excellent. Regarding complete tumor ablation, EUS-RFA appeared to be superior to EUS-EA. Although EUS-RFA has been reported as a safe treatment for pancreatic cancers, its effectiveness remains inadequate. Some studies have examined the effectiveness of EUS-guided injection ablation therapy for pancreatic cystic neoplasms (PCNs) and have reported CR rates that range from 35% to 79%. Alcohol-free chemotherapeutic agent ablation appears to be effective, with a low risk of AEs. However, studies on the effectiveness of EUS-RFA for PCNs are limited. In the future, EUS-guided ablation therapy could become a more widely used approach for potentially malignant and malignant pancreatic lesions.
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Affiliation(s)
- Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
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Kerdsirichairat T, Shin EJ. Endoscopic ultrasound guided interventions in the management of pancreatic cancer. World J Gastrointest Endosc 2022; 14:191-204. [PMID: 35634485 PMCID: PMC9048490 DOI: 10.4253/wjge.v14.i4.191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 08/09/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
There has been a growing interest in developing endoscopic ultrasound (EUS)-guided interventions for pancreatic cancer, some of which have become standard of care. There are two main factors that drive these advancements to facilitate treatment of patients with pancreatic cancer, ranging from direct locoregional therapy to palliation of symptoms related to inoperable pancreatic cancer. Firstly, an upper EUS has the capability to access the entire pancreas-lesions in the pancreatic head and uncinate process can be accessed from the duodenum, and lesions in the pancreatic body and tail can be accessed from the stomach. Secondly, there has been a robust development of devices that allow through-the-needle interventions, such as placement of fiducial markers, brachytherapy, intratumoral injection, gastroenterostomy creation, and ablation. While these techniques are rapidly emerging, data from a multicenter randomized controlled trial for some procedures are awaited prior to their adoption in clinical settings.
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Affiliation(s)
| | - Eun Ji Shin
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, United States
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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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El Sayed G, Frim L, Franklin J, McCrudden R, Gordon C, Al-Shamma S, Kiss S, Hegyi P, Erőss B, Hegyi PJ. Endoscopic ultrasound-guided ethanol and radiofrequency ablation of pancreatic insulinomas: a systematic literature review. Therap Adv Gastroenterol 2021; 14:17562848211042171. [PMID: 34819995 PMCID: PMC8606734 DOI: 10.1177/17562848211042171] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/15/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Insulinoma is the most common neuroendocrine neoplasm of the pancreas, characterised by hypoglycaemic symptoms. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and ethanol ablation (EUS-EA) are novel methods for treating insulinoma.We aimed to perform a systematic review to assess the efficacy and safety of EUS-guided ablation techniques for pancreatic insulinomas. METHODS We systematically searched for articles detailing EUS-guided ablations of insulinomas. We performed a qualitative analysis and summarised data on the efficacy and safety of EUS-RFA and EUS-EA techniques. RESULTS In total, we identified 35 case reports and case series describing 75 patients with insulinomas treatment with EUS-guided ablation. Twenty-seven patients were treated with EUS-RFA, 47 patients with EUS-EA, and 1 patient received EUS-EA and EUS-RFA in the same session. In total, 84 insulinomas were ablated (EUS-RFA: 31, EUS-EA: 53). Most insulinomas were in the head of the pancreas (40%). The clinical success rate for EUS-guided ablation techniques was 98.5%. The median glucose level was 1.95 (Q1-Q3: 1.69-2.13) mmol/L before ablation compared to 6.20 (Q1-Q3: 5.30-7.05) mmol/L after treatment. The median insulin and C-peptide levels before and after RFA/EA were 230 (Q1-Q2: 120-257) pmol/L and 41 (Q1-Q2 35-42) pmol/L; 2077 (Q1-Q2 1644-2459) pmol/L and 819 (Q1-Q2 696-1072) pmol/L, respectively. There were eleven adverse events: seven abdominal pain, two mild acute pancreatitis, one necrotising acute pancreatitis and one local hematoma. All patients recovered, and there were no periprocedural deaths. CONCLUSIONS EUS-guided ablation of insulinoma seems to be a safe and effective treatment and is an alternative to surgical resection in selected cases.
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Affiliation(s)
- Ghassan El Sayed
- The Royal Bournemouth Hospital, University Hospital Dorset, Bournemouth, UK
| | - Levente Frim
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Jamie Franklin
- The Royal Bournemouth Hospital, University Hospital Dorset, Institute of Medical Imaging and Visualisation, Bournemouth, UKLevente Frim
| | - Raymond McCrudden
- The Royal Bournemouth Hospital, University Hospital Dorset, Bournemouth, UK
| | - Charles Gordon
- The Royal Bournemouth Hospital, University Hospital Dorset, Bournemouth, UK
| | - Safa Al-Shamma
- The Royal Bournemouth Hospital, University Hospital Dorset, Bournemouth, UK
| | - Szabolcs Kiss
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary
- Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Jenő Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti Street 12, Pecs H-7624, Hungary
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13
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Abstract
Ablative therapies for locoregional treatment of pancreatic neoplastic lesions developed over the last decade to be applied during surgery are now becoming also available to be utilized under endoscopic ultrasound (EUS) guidance. The advantage of this approach is clear because of the close proximity of the EUS transducer to the target lesion, coupled with developments of specifically designed ablation devices, making the procedure minimally invasive, and potentially sparing patients from the morbidity of this method when performed surgically. EUS-guided ablative techniques that have been applied to pancreatic neoplastic cysts, pancreatic functional and non-functional neuroendocrine neoplasms and pancreatic ductal adenocarcinoma include ethanol injection, radiofrequency ablation (RFA), a combination of bipolar RFA and cryoablation, laser therapy (LT) and photodynamic therapy (PDT). Up to now, most of these procedures have been applied to patients at high surgical risk or who refused surgery. However, more studies evaluating some of these treatments also in selected patients not at surgical risk are becoming available. These studies will pave the road to apply this therapeutic approach to a more extensive number of patients, alone or in association with other therapies, such as immunomodulating drugs. The present manuscript will critically review the available evidence in the field of EUS-guided local ablative treatment of solid and cystic pancreatic neoplasms.
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Affiliation(s)
- Mihai Rimbaș
- Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania.,Department of Internal Medicine, Carol Davila University of Medicine, Bucharest, Romania
| | - Gianenrico Rizzatti
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy - .,CERTT, Center for Endoscopic Research Therapeutics and Training, Catholic University, Rome, Italy
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14
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Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV. Multiple Endocrine Neoplasia Type 1: Latest Insights. Endocr Rev 2021; 42:133-170. [PMID: 33249439 PMCID: PMC7958143 DOI: 10.1210/endrev/bnaa031] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Indexed: 02/06/2023]
Abstract
Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics, and molecular biology specialists. There have been 2 major clinical practice guidance papers published in the past 2 decades, with the most recent published 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature, and those data are discussed in this review. The genetic and molecular interactions of the MEN1-encoded protein menin with transcription factors and chromatin-modifying proteins in cell signaling pathways mediated by transforming growth factor β/bone morphogenetic protein, a few nuclear receptors, Wnt/β-catenin, and Hedgehog, and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1-related conditions in germline MEN1 mutation-negative patients. There is rapidly accumulating knowledge about clinical presentation in children, adolescents, and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuroendocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.
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Affiliation(s)
| | | | - Nancy D Perrier
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Gerlof D Valk
- University Medical Center Utrecht, CX Utrecht, the Netherlands
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15
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Yousaf MN, Ehsan H, Muneeb A, Wahab A, Sana MK, Neupane K, Chaudhary FS. Role of Radiofrequency Ablation in the Management of Unresectable Pancreatic Cancer. Front Med (Lausanne) 2021; 7:624997. [PMID: 33644089 PMCID: PMC7904870 DOI: 10.3389/fmed.2020.624997] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 12/11/2020] [Indexed: 12/15/2022] Open
Abstract
Pancreatic cancer is one of the most aggressive malignancies of the digestive tract and carries a poor prognosis. The majority of patients have advanced disease at the time of diagnosis. Surgical resection offers the only curative treatment, but only a small proportion of patients can undergo surgical resection. Radiofrequency ablation (RFA) is a well-known modality in the management of solid organ tumors, however, its utility in the management of pancreatic cancer is under investigation. Since the past decade, there is increasing use of RFA as it provides a feasible palliation treatment in the management of unresectable pancreatic cancer. RFA causes tumor cytoreduction through multiple mechanisms such as coagulative necrosis, protein denaturation, and activation of anticancer immunity. The safety profile of RFA is controversial because of the high risk for complications, however, small prospective and retrospective studies have shown promising results in its applicability for palliative management of unresectable pancreatic malignancies. In this review, we discuss different approaches of RFA, their indications, technical accessibility, safety, and major complications in the management of unresectable pancreatic cancer.
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Affiliation(s)
- Muhammad Nadeem Yousaf
- Department of Medicine, MedStar Union Memorial Hospital, Baltimore, MD, United States
- MedStar Franklin Square Medical Center, Baltimore, MD, United States
- MedStar Good Samaritan Hospital, Baltimore, MD, United States
- MedStar Harbor Hospital, Baltimore, MD, United States
| | - Hamid Ehsan
- Department of Medicine, MedStar Union Memorial Hospital, Baltimore, MD, United States
| | - Ahmad Muneeb
- Department of Medicine, Faisalabad Medical University, Faisalabad, Pakistan
| | - Ahsan Wahab
- Department of Medicine, Baptist Medical Center South, Montgomery, AL, United States
| | - Muhammad K. Sana
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Karun Neupane
- Department of Medicine, Manipal College of Medical Sciences, Pokhara, Nepal
| | - Fizah S. Chaudhary
- Department of Medicine, MedStar Union Memorial Hospital, Baltimore, MD, United States
- MedStar Franklin Square Medical Center, Baltimore, MD, United States
- MedStar Good Samaritan Hospital, Baltimore, MD, United States
- MedStar Harbor Hospital, Baltimore, MD, United States
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16
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Larghi A, Rimbaș M, Rizzatti G, Carbone C, Gasbarrini A, Costamagna G, Alfieri S, Tortora G. Endoscopic ultrasound-guided therapies for pancreatic solid tumors: An overview. Semin Oncol 2021; 48:95-105. [PMID: 33608132 DOI: 10.1053/j.seminoncol.2021.01.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 01/16/2021] [Indexed: 12/14/2022]
Abstract
The close proximity of the endoscopic ultrasound (EUS) probe to the pancreas, coupled with the ease with which a needle can be inserted into a pancreatic lesion, have contributed to the development of EUS-guided therapies for both adenocarcinoma and neuroendocrine pancreatic neoplasms. EUS-guided fine needle injection of different types of drugs, implantation of fiducial markers to facilitate stereotactic body radiation therapy or of radioactive seeds to perform brachytherapy, and the use of different thermal and nonthermal ablation devices and techniques have all been tested in preliminary human studies. This manuscript will present the available evidence accumulated thus far in the field of EUS-guided oncological treatment of pancreatic solid tumors, along with a look into possible future applications.
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Affiliation(s)
- Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
| | - Mihai Rimbaș
- Gastroenterology Department, Colentina Clinical Hospital, Carol Davila University of Medicine, Bucharest, Romania
| | - Gianenrico Rizzatti
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy; Gastroenterology Division, Fondazione Policlinico Universitario A. Gemelli, Catholic University, IRCCS, Rome, Italy
| | - Carmine Carbone
- Oncological Division, Fondazione Policlinico Universitario A. Gemelli, Catholic University, IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Gastroenterology Division, Fondazione Policlinico Universitario A. Gemelli, Catholic University, IRCCS, Rome, Italy
| | - Guido Costamagna
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University, Rome, Italy; IHU-USIAS, University of Strasbourg, Strasbourg, France
| | - Sergio Alfieri
- Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University, Rome, Italy
| | - Giampaolo Tortora
- Oncological Division, Fondazione Policlinico Universitario A. Gemelli, Catholic University, IRCCS, Rome, Italy
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17
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Di Matteo FM, Stigliano S. Endoscopic Ultrasound-Guided Therapies for Solid Pancreatic Tumors. ENDOSCOPIC ULTRASOUND MANAGEMENT OF PANCREATIC LESIONS 2021:179-189. [DOI: 10.1007/978-3-030-71937-1_14] [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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18
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Safety and efficacy of EUS-guided ablation of pancreatic lesions with ethanol versus ethanol with paclitaxel: A systematic review and meta-analysis. Endosc Ultrasound 2021. [PMID: 36255024 DOI: 10.4103/eus-d-20-00185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/17/2025] Open
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19
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Mosquera-Klinger G, Carvajal JJ. Endoscopic ultrasound-guided ethanol ablation for the management of a symptomatic pancreatic insulinoma. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 113:48-51. [PMID: 33226258 DOI: 10.17235/reed.2020.7109/2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION pancreatic insulinoma is a sporadic, usually benign, frequently solitary tumor that is smaller than 20 mm. When it is functioning, patients present with symptoms of hypoglycemia secondary to insulin hypersecretion. The diagnosis is clinical, with biochemical and radiological confirmation. Surgery is the management of choice, although endoscopic ultrasound-guided ablation is currently being developed. MATERIAL AND METHODS we present a prospective case series of pancreatic insulinoma patients with symptoms of severe hypoglycemia, who were treated with endoscopic ultrasound-guided ethanol ablation as an alternative to surgical management. RESULTS technical and clinical success was achieved in all cases and there were no complications associated with the procedure. CONCLUSION the treatment of symptomatic insulinoma by endoscopic ultrasound-guided ethanol ablation could be a safe and effective alternative to surgical management in non-surgical patients or those who refuse surgery.
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Affiliation(s)
| | - Jhon Jaime Carvajal
- Gastroenterología y Endoscopia Digestiva, Hospital Pablo Tobón Uribe, Colombia
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20
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Rimbaş M, Horumbă M, Rizzatti G, Crinò SF, Gasbarrini A, Costamagna G, Larghi A. Interventional endoscopic ultrasound for pancreatic neuroendocrine neoplasms. Dig Endosc 2020; 32:1031-1041. [PMID: 31995848 DOI: 10.1111/den.13635] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Revised: 12/25/2019] [Accepted: 01/22/2020] [Indexed: 02/06/2023]
Abstract
The proximity of the endoscopic ultrasound (EUS) transducer to the pancreas and the possibility to place needles or other accessories into a target located adjacent to the wall of the GI tract have encouraged researchers to develop various EUS-guided local treatments directed towards pancreatic neuroendocrine neoplasms (PanNENs). The use of pre-operative EUS-guided tattooing or fiducial marker placement to facilitate intraoperative tumor localization has proven effective in reducing operative time of laparoscopic surgeries. To reduce the mortality and morbidity rates of surgical resection, which is presently the mainstay treatment of PanNENs. EUS-guided loco-regional treatments, such as injection of alcohol and radiofrequency ablation have been proposed and results are hitherto promising. The present paper summarizes currently available data in the field of EUS-guided interventions to pancreatic neuroendocrine tumors, as well as possible future applications.
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Affiliation(s)
- Mihai Rimbaş
- Digestive Endoscopy Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.,Gastroenterology and Internal Medicine Departments, Colentina Clinical Hospital, Carol Davila University of Medicine, Bucharest, Romania
| | - Mihaela Horumbă
- Gastroenterology and Internal Medicine Departments, Colentina Clinical Hospital, Carol Davila University of Medicine, Bucharest, Romania
| | - Gianenrico Rizzatti
- Digestive Endoscopy Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University Hospital of Verona, Verona, Italy
| | - Antonio Gasbarrini
- Gastroenterology Division, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University, Rome, Italy
| | - Guido Costamagna
- and, Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University, Rome, Italy.,IHU-USIAS, University of Strasbourg, Strasbourg, France
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.,CERTT, Center for Endoscopic Research Therapeutics and Training, Catholic University, Rome, Italy
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21
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Kodama R, Koh Y, Midorikawa H, Yokota Y, Saegusa H, Ushimaru H. A case of recurrence of a solid pseudopapillary neoplasm of the pancreas effectively treated with proton beam radiotherapy. Clin J Gastroenterol 2020; 14:375-381. [PMID: 33052580 DOI: 10.1007/s12328-020-01262-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 10/05/2020] [Indexed: 02/08/2023]
Abstract
We report a case of a male in his 50 s who underwent pancreaticoduodenectomy for solid pseudopapillary neoplasm (SPN) of the pancreas at 30 years. He developed a liver abscess 15 years after the surgery, and CT scan revealed a swollen retroperitoneum lymph node and a tumor in the liver. Symptoms, including abdominal distension, appetite loss, and epigastric pain, appeared due to lymph node metastasis. Endoscopic ultrasonography-guided fine-needle aspiration against the lymph node revealed SPN recurrence. The tumor had invaded the common hepatic artery, and surgery was not indicated. Chemotherapy of Gemcitabine/nab-Paclitaxel biweekly was performed 8 times; however, no reduction in tumor size was observed, and the patient's symptoms worsened. Proton beam therapy (67.5 GyE in 25 fractions) was subsequently performed for lymph node metastasis, and led to a gradual reduction in lymph node metastasis, and an improvement in symptoms. No re-expansion of lymph node metastasis has been observed 3 years after proton beam therapy. Since SPN is low malignancy and most cases can be expected to be cured by surgery, there is currently no standard treatment of unresectable SPN. This case is the first report of proton beam therapy for SPN, and was considered to be effective.
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Affiliation(s)
- Ryo Kodama
- Department of Gastroenterology, JA Nagano Koseiren Minaminagano Medical Center, Shinonoi General Hospital, Nagano, Japan.
| | - Youshin Koh
- Department of Gastroenterology, JA Nagano Koseiren Minaminagano Medical Center, Shinonoi General Hospital, Nagano, Japan
| | - Hajime Midorikawa
- Department of Gastroenterology, JA Nagano Koseiren Minaminagano Medical Center, Shinonoi General Hospital, Nagano, Japan
| | - Yukiko Yokota
- Department of Gastroenterology, JA Nagano Koseiren Minaminagano Medical Center, Shinonoi General Hospital, Nagano, Japan
| | - Hisanobu Saegusa
- Department of Gastroenterology, JA Nagano Koseiren Minaminagano Medical Center, Shinonoi General Hospital, Nagano, Japan
| | - Hiroyasu Ushimaru
- Department of Gastroenterology, JA Nagano Koseiren Minaminagano Medical Center, Shinonoi General Hospital, Nagano, Japan
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22
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Zhang L, Tan S, Huang S, Zhong C, Lü M, Peng Y, Tang X. The safety and efficacy of endoscopic ultrasound-guided ablation therapy for solid pancreatic tumors: a systematic review. Scand J Gastroenterol 2020; 55:1121-1131. [PMID: 32730715 DOI: 10.1080/00365521.2020.1797870] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/26/2020] [Accepted: 07/14/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Recently, endoscopic ultrasound (EUS)-guided ablation therapy, as a minimally invasive technique, has shown its potential to substitute surgery in treating solid pancreatic tumors, such as small potential malignant pancreatic tumors, small insulinomas and locally advanced pancreatic ductal adenocarcinoma (LAPDAC). Therefore, we conducted this systematic review to assess the safety and efficacy of EUS-guided ablation therapy for solid pancreatic tumors. METHODS We conducted a comprehensive search of PubMed, Embase, Cochrane library and Web of Science databases from inception to February 2020. The endpoints were clinical success and complications rates. The pooled event rate was calculated using Comprehensive Meta Analysis software. RESULTS Fourteen studies with a total of 158 patients were included in our final analysis. The major types of solid pancreatic tumors were nonfunction pancreatic neuroendocrine tumors (n = 78, 49.4%), LAPDAC (n = 48, 30.4%) and insulinomas (n = 26, 16.5%). Overall, the pooled clinical success rate was 85.9% (95% confidence interval (CI): 75.4-92.4%, I 2 = 25.18%), pooled complications rate was 29.1% (95% CI: 18.6-42.3%, I 2 = 50.40%). Subgroup analysis was performed based on ablation methods, which showed clinical success rate for radiofrequency ablation (RFA) was 83.5% (95% CI: 67.9-92.4%), and 87.9% (95% CI: 66.2-96.4%) for ethanol ablation (EA). In terms of complications rate, it was 32.2% (95% CI: 19.4-48.4%) for RFA, and 21.2% (95% CI: 6.8-49.9%) for EA. CONCLUSIONS EUS-guided ablation therapy is a promising alternative treatment for solid pancreatic tumors, especially for p-NETs and insulinomas < 2 cm, with rarely severe complications. Further prospective studies with long-term follow-up are warranted in future.
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Affiliation(s)
- Lu Zhang
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Shali Tan
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Shu Huang
- Department of Gastroenterology, The People's Hospital of Lianshui, Huaian, China
| | - Chunyu Zhong
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Muhan Lü
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yan Peng
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiaowei Tang
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China
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23
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Liao H, Zeng Y, Liao S, Chu Y, Zhou Y, Wang Y. Three Birds with One Stone: Injectable CaC 2 Nanobombs with Triple Effects for Minimally Invasive Tumor Chemical Ablation. ACS APPLIED BIO MATERIALS 2020; 3:3809-3816. [PMID: 35025251 DOI: 10.1021/acsabm.0c00383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Percutaneous chemical ablation (PCA) is the oldest and most established technique for treating small solid tumors in organs. It has been widely used in clinics even on an outpatient basis. However, compared with the emerging microwave or magnetic hyperthermal ablation, PCA is faced with relatively poor necrosis results and needs to repeat multiple sessions. Inspired by the three effects in the bomb's explosive process, we herein expect to combine calcium carbide (CaC2) nanoparticles into the PCA technique to generate local explosion within tumor tissues, leading to three killing effects against tumors to further improve the ablation efficacy of PCA. Through an efficient wet milling procedure with poly(ethylene glycol), three kinds of nanobombs including CaC2, calcium oxide (CaO), and calcium hydroxide (Ca(OH)2) were fabricated, and they all exhibited desirable suspension stability. Among these nanobombs, in particular CaC2 nanobombs showed a synergistic effect that the generation of ethyne gas bubbles could facilitate the most rapid diffusion of hyperthermia. Also, CaC2 nanobombs offered the powerful ability to cause the sudden rise of local high temperature and pH value. According to the in vivo mice tumor excision trial, the tumors of 75% of cases that received CaC2 treatment were destroyed and eradicated, exhibiting the excellent ablation ability of CaC2 nanobombs against small solid tumors planted in mice.
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Affiliation(s)
- Hongguang Liao
- Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Yuting Zeng
- Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Shenglong Liao
- Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Yanji Chu
- Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - You Zhou
- Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Yapei Wang
- Department of Chemistry, Renmin University of China, Beijing 100872, China
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24
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Yao C, Wang X, Zhang Y, Kong J, Gao J, Ke S, Ding X, Xin Z, Xu W, Wang S, Sun W. Treatment of Insulinomas by Laparoscopic Radiofrequency Ablation: Case Reports and Literature Review. Open Med (Wars) 2020; 15:84-91. [PMID: 32104725 PMCID: PMC7029651 DOI: 10.1515/med-2020-0013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 11/20/2019] [Indexed: 12/12/2022] Open
Abstract
Despite its rarity, insulinoma is the most common type of pancreatic endocrine neoplasm, with an occurrence of 1 to 5 per million per year in the population. Surgical resection or enucleation is the first line of curative treatment choice for insulinoma. Eight patients with symptomatic insulinomas treated by radiofrequency ablation have been described since 2009. In the past two years, we treated two patients with symptomatic insulinomas (one in the pancreatic tail and the other in the pancreatic neck) successfully using laparoscopic radiofrequency ablation. Both patients achieved complete elimination without any significant complications. Our study suggests laparoscopic radiofrequency ablation could be developed as a safe and effective alternative treatment to surgery for the patients with insulinomas who refuse or are not eligible for surgery.
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Affiliation(s)
- Changyu Yao
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Xiangtao Wang
- Department of General Surgery, Zhanhua People's Hospital, Shandong Province, China
| | - Yongli Zhang
- Department of General Surgery, Zhanhua People's Hospital, Shandong Province, China
| | - Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Jun Gao
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Shan Ke
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Xuemei Ding
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Zonghai Xin
- Department of General Surgery, Zhanhua People's Hospital, Shandong Province, China
| | - Wenlei Xu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Shaohong Wang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, No. 5, Jingyuan Street, Beijing 100043, China
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25
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Lin H, Chang C, Chen M. Endoscopic ultrasonography‐guided ethanol ablation of pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 disease following complicated total pancreatectomy. ADVANCES IN DIGESTIVE MEDICINE 2019. [DOI: 10.1002/aid2.13161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Hsiang‐Hung Lin
- Division of Gastroenterology and Hepatology, Department of Internal MedicineMacKay Memorial Hospital Taipei Taiwan
- Department of NursingMacKay Junior College of Medicine Nursing and Management Taipei Taiwan
- Department of MedicineMacKay Medical College New Taipei City Taiwan
| | - Chen‐Wang Chang
- Division of Gastroenterology and Hepatology, Department of Internal MedicineMacKay Memorial Hospital Taipei Taiwan
- Department of NursingMacKay Junior College of Medicine Nursing and Management Taipei Taiwan
- Department of MedicineMacKay Medical College New Taipei City Taiwan
| | - Ming‐Jen Chen
- Division of Gastroenterology and Hepatology, Department of Internal MedicineMacKay Memorial Hospital Taipei Taiwan
- Department of NursingMacKay Junior College of Medicine Nursing and Management Taipei Taiwan
- Department of MedicineMacKay Medical College New Taipei City Taiwan
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26
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Egorov AV, Vasilyev IA, Musayev GH, Mironova AV. The role of microwave ablation in management of functioning pancreatic neuroendocrine tumors. Gland Surg 2019; 8:766-772. [PMID: 32042685 DOI: 10.21037/gs.2019.12.07] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Surgical resection is considered to be the only potentially curative option for patients with pancreatic neuroendocrine tumors (pNETs). High risk rates of perioperative complications make minimally invasive ablative techniques a novel perspective and alternative treatment option for pancreatic neuroendocrine tumors. This study aims to present the first experience of using a microwave ablation in management of pNETs. Methods Sechenov University has an experience of treating more than 400 patients with hormone-producing tumors of the pancreas, 7 of which were treated by microwave ablation (MWA). Results In all patients that underwent MWA, a regression of hormonal symptomatic was achieved. Two patients required readmission a month later for draining of pseudocyst and abscess. Conclusions The exact role of microwave ablation in the treatment of non-metastatic pancreatic neuroendocrine tumors has not been defined yet. There is a lack of large prospective randomized studies and the reason for this is that local tumor destruction is indicated in selected cases only, thus making it difficult to analyze a large group of patients and assess long-term results of the treatment. However, microwave ablation allows to take a better control of symptoms in patients with hormone overproduction and in those with high risk of postoperative complications.
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Affiliation(s)
- Alexey Victorovich Egorov
- Abdominal Surgery Department, University Clinical Hospital Nº1 of Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Ivan Alekseevich Vasilyev
- Abdominal Surgery Department, University Clinical Hospital Nº1 of Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Gaziyav Hadisovich Musayev
- General Surgery, University Clinical Hospital Nº1 of Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Anna Victorovna Mironova
- Faculty Surgery, University Clinical Hospital Nº1 of Sechenov First Moscow State Medical University, Moscow, Russian Federation
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27
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Grading by the Ki-67 Labeling Index of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Specimens of Pancreatic Neuroendocrine Tumors Can Be Underestimated. Pancreas 2018; 47:1296-1303. [PMID: 30211805 DOI: 10.1097/mpa.0000000000001157] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES There is an increasing need for grading with small endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) specimens for the proper diagnosis and therapy selection of patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, our understanding of EUS-FNAB specimen grading is limited compared with surgically resected specimens. METHODS We retrospectively determined Ki-67 labeling index (LI) of 33 matched EUS-FNAB and surgically resected PanNETs with digital image analyzer. Pairwise grades between the matched biopsy and surgically resected PanNET specimens were compared. RESULTS The mean Ki-67 LI was higher in surgically resected PanNET specimens (5.5%) than in biopsy specimens (3.2%; P = 0.022). There was moderate agreement between the Ki-67 LI grades when individually evaluated matched biopsy and resected specimen pairs were compared (κ value = 0.62; P < 0.0001). However, discordance was noted in 6 cases (18%), and all of them were either grade 2 or 3 in resected PanNETs. CONCLUSIONS Although Ki-67 LI grading of EUS-FNAB specimens may be concordant with that of matched surgically resected specimens in a large proportion of the PanNET cases, Ki-67 LI grading of EUS-FNAB specimens should be carefully applied in clinical practice because of the possibility of grading underestimation with grade 2 to 3 PanNET cases.
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Escartín R, Brun N, García Monforte MN, Ferreres JC, Corripio R. Insulinoma: A Rare Cause of Hypoglycemia in Childhood. AMERICAN JOURNAL OF CASE REPORTS 2018; 19:1121-1125. [PMID: 30237390 PMCID: PMC6161565 DOI: 10.12659/ajcr.910426] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patient: Male, 11 Final Diagnosis: Insulinoma Symptoms: Dizziness • psychological issues Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic
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Affiliation(s)
- Rocío Escartín
- Department of Pediatric Endocrinology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Nuria Brun
- Department of Surgery, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - M Nieves García Monforte
- Department of Surgery, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Joan Carles Ferreres
- Department of Pathology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Raquel Corripio
- Department of Pediatric Endocrinology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
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Choi JH, Park DH, Kim MH, Hwang HS, Hong SM, Song TJ, Lee SS, Seo DW, Lee SK. Outcomes after endoscopic ultrasound-guided ethanol-lipiodol ablation of small pancreatic neuroendocrine tumors. Dig Endosc 2018; 30:652-658. [PMID: 29575213 DOI: 10.1111/den.13058] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 03/13/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Little is known about the standard care of small (<2 cm in diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study was to determine the clinical outcomes of small PNET after endoscopic ultrasound (EUS)-guided ethanol-lipiodol ablation (EUS-ELA). METHODS In this prospective cohort study, consecutive patients who underwent EUS-ELA for PNET were enrolled and were followed for ≥3 years. Treatment efficacy was the primary outcome measure. RESULTS In total, 33 patients who had 40 pathologically confirmed PNET (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS-ELA sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6 sessions per tumor), which included 40 initial sessions and 23 repeated sessions owing to incomplete ablation. Median actual volume of ethanol-lipiodol mixture injected per session was 1.1 mL (IQR 0.8-1.9 mL). Complete ablation was achieved in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%) sessions of EUS-ELA. Lipiodol retention within tumor had better treatment outcomes (P = 0.004). Rate of procedure-related adverse events was 3.2%. No malignancy or lymph node metastasis was discovered during a median follow up of 42 months (IQR 39-46 months). CONCLUSIONS We found that EUS-ELA was a safe and effective alternative option in the management of PNET <2.0 cm in diameter; 60% of patients achieved complete ablation. Lipiodol retention within tumor may be a useful early predictor of treatment effectiveness. Trial registered at ClinicalTrials.gov (NCT 01902238).
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Affiliation(s)
- Jun-Ho Choi
- Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital, Cheonan, Korea
| | - Do Hyun Park
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Myung-Hwan Kim
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hee Sang Hwang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Tae Jun Song
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sang Soo Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong-Wan Seo
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung Koo Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Paik WH, Lee SH, Jang S. Future Perspectives on Endoscopic Ultrasonography-Guided Therapy for Pancreatic Neoplasm. Clin Endosc 2018; 51:229-234. [PMID: 29774696 PMCID: PMC5997079 DOI: 10.5946/ce.2018.063] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 04/26/2018] [Accepted: 04/27/2018] [Indexed: 02/07/2023] Open
Abstract
Endoscopic ultrasonography (EUS)-guided therapy with ethanol injection or catheter-based radiofrequency ablation for pancreatic neoplasm has been conducted as a potential alternate treatment modality for patients who are not eligible for surgery. On the basis of the limited number of studies available, EUS-guided ablation therapy with the aforementioned methods for small pancreatic neoplasms has demonstrated promising technical feasibility and safety profiles. To be considered as a legitimate alternative option to surgery, however, EUS-guided ablation therapy must provide a long-term efficacy profile along with the consensus among experts regarding its treatment parameter. This review focuses on the clinical issues and future perspectives of EUS-guided therapy for pancreatic neoplasm.
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Affiliation(s)
- Woo Hyun Paik
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sunguk Jang
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
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Brown E, Watkin D, Evans J, Yip V, Cuthbertson DJ. Multidisciplinary management of refractory insulinomas. Clin Endocrinol (Oxf) 2018; 88:615-624. [PMID: 29205458 DOI: 10.1111/cen.13528] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 11/12/2017] [Accepted: 11/29/2017] [Indexed: 12/20/2022]
Abstract
Insulinomas are predominantly benign (~90%), pancreatic neuroendocrine tumours characterized by hyperinsulinaemic hypoglycaemia. They usually present as a small (<2 cm), well-demarcated, solitary nodule that can arise in any part of the organ. Treatment for sporadic insulinomas is generally aimed at curative surgical resection with special consideration in genetic syndromes. Patients with significant hypoglycaemia can pose a difficult management challenge. In isolated cases where the patient is not medically fit for surgery or with metastatic spread, other treatment options are employed. Medical therapy with diazoxide or somatostatin analogues is commonly used first line for symptom control, albeit with variable efficacy. Other medical options are emerging, including newer targeted biological therapies, including everolimus (an mTOR inhibitor), sunitinib (a tyrosine kinase inhibitor) and pasireotide, a multisomatostatin receptor ligand. Pasireotide and everolimus both cause hyperglycaemia by physiological mechanisms synergistic with its antitumour/antiproliferative effects. Minimally invasive treatment modalities such as ethanol ablation are available in selected cases (particularly in patients unfit for surgery), peptide receptor radionuclide therapy (PRRT) can effectively control tumour growth or provide symptomatic benefit in metastatic disease, while cytotoxic chemotherapy can be used in patients with higher-grade tumours. This review considers the developments in the medical and other nonsurgical management options for cases refractory to standard medical management. Early referral to a dedicated neuroendocrine multidisciplinary team is critical considering the array of medical, oncological, interventional radiological and nuclear medical options. We discuss the evolving armamentarium for insulinomas when standard medical therapy fails.
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Affiliation(s)
- Emily Brown
- Obesity and Endocrinology Research Group, University Hospital Aintree, University of Liverpool, Liverpool, UK
| | - Daniel Watkin
- Obesity and Endocrinology Research Group, University Hospital Aintree, University of Liverpool, Liverpool, UK
| | - Jonathan Evans
- Department of Radiology, The Royal Liverpool and Broadgreen University Hospital NHS Trust, University of Liverpool, Liverpool, UK
| | - Vincent Yip
- Pancreatic Biomedical Research Unit, The Royal Liverpool and Broadgreen University Hospital NHS Trust, University of Liverpool, Liverpool, UK
| | - Daniel J Cuthbertson
- Obesity and Endocrinology Research Group, University Hospital Aintree, University of Liverpool, Liverpool, UK
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Qin S, Liu Y, Ning H, Tao L, Luo W, Lu D, Luo Z, Qin Y, Zhou J, Chen J, Jiang H. EUS-guided lauromacrogol ablation of insulinomas: a novel treatment. Scand J Gastroenterol 2018; 53:616-620. [PMID: 29141488 DOI: 10.1080/00365521.2017.1402206] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 11/03/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS EUS-guided ablation with ethanol has been used to treat insulinoma since 2006 as a minimally invasive alternative for those who are unwilling or unsuitable for surgeries. However, pancreatic fistula, pancreatitis and other adverse effects were found after the procedure in these patients. Herein, we aimed to find a novel feasible injection. METHODS Seven patients with different chief complaints were diagnosed with insulinoma by symptoms, lab results and pathology results from EUS fine needle aspiration. All the patients refused to have surgeries and were treated by EUS-guided ablation with lauromacrogol. The injection volume was calculated by tumor size. All the patients were followed up by at least 1 month to see if there is any adverse effect. Blood glucose (BG), insulin and C-peptide levels were monitored before and after the procedure. RESULTS Insulinoma size ranged from 0.76 cm ×0.84 cm to 3.39 cm ×1.84 cm. With a mean injection volume of 1.9 ml (range from 0.9 to 3.9 ml), all the patients showed relief in symptoms after the procedure. During the follow up, their BG, insulin and C-peptide levels went back to normal. None of the patients had any adverse effect. CONCLUSIONS EUS-guided ablation with lauromacrogol showed good treatment results and received no adverse effect after the procedure. Hence, we consider it as an effective and safe method to treat insulinoma.
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Affiliation(s)
- Shanyu Qin
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Yongru Liu
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Hongjian Ning
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Lin Tao
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Wei Luo
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Donghong Lu
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Zuojie Luo
- b Endocrinology Department , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Yingfen Qin
- b Endocrinology Department , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Jia Zhou
- b Endocrinology Department , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Junqiang Chen
- c Department of Gastrointestinal Surgery , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
| | - Haixing Jiang
- a Department of Gastroenterology , First Affiliated Hospital of Guangxi Medical University , Nanning , P.R. China
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Dugarova RS, Berelavichus SV, Kaldarov AR, Gorin DS. [Physical minimally invasive treatment of pancreatic insulinoma]. Khirurgiia (Mosk) 2018:94-97. [PMID: 29697692 DOI: 10.17116/hirurgia2018494-97] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- R S Dugarova
- Vishnevsky Institute of Surgery of Healthcare Ministry of the Russian Federation, Moscow, Russia
| | - S V Berelavichus
- Vishnevsky Institute of Surgery of Healthcare Ministry of the Russian Federation, Moscow, Russia
| | - A R Kaldarov
- Vishnevsky Institute of Surgery of Healthcare Ministry of the Russian Federation, Moscow, Russia
| | - D S Gorin
- Vishnevsky Institute of Surgery of Healthcare Ministry of the Russian Federation, Moscow, Russia
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Mele C, Brunani A, Damascelli B, Tichà V, Castello L, Aimaretti G, Scacchi M, Marzullo P. Non-surgical ablative therapies for inoperable benign insulinoma. J Endocrinol Invest 2018; 41:153-162. [PMID: 28755102 DOI: 10.1007/s40618-017-0738-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Accepted: 07/22/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE Benign insulinoma is the most common functioning neuroendocrine tumor of the pancreas. The gold-standard therapeutic approach for insulinoma is surgery, which allows for tumor removal, histology and immunochemical analyses. If surgery is not feasible, minimally invasive ablative procedures performed by interventional radiology can lead to partial or complete remission of hormone hypersecretion and tumor control in insulinoma patients. METHODS We performed a review of existing literature on non-chemotherapeutic/radioactive ablative techniques employed for the treatment of benign, otherwise inoperable, pancreatic insulinoma. For this purpose, feasibility, effectiveness and safety of ablative treatments for pancreatic insulinoma were reviewed from literature data published from 1982 to date. RESULTS A total of 44 insulinoma cases treated with non-surgical ablative techniques were desumed, and divided as follows: 7 cases of tumor embolization, 26 ethanol ablations, 7 radiofrequency ablations, 2 high intensity focused ultrasound ablation, 1 irreversible electroporation and 1 percutaneous microwave ablation. Most cases involved single insulinoma, predominantly located in the pancreas head and body. In the majority of patients, ablation was chosen instead of surgery due to severe comorbidities. After an average follow-up of 16 months, the overall success rate of non-surgical ablative treatments of insulinoma was 84%, the recurrence/persistence rate was 16%, and transient adverse events were noted in 23% of cases. Adverse events were usually self-limiting and medically manageable. CONCLUSIONS Non-surgical ablation is a feasible, safe and repeatable procedure in patients with pancreatic insulinoma, who are not candidate to surgery or refuse it. Partial or complete control of symptoms and tumor growth is experienced by the majority of patients.
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Affiliation(s)
- C Mele
- Division of General Medicine, IRCCS Istituto Auxologico Italiano, Ospedale S. Giuseppe, Via Cadorna 90, 28824, Piancavallo, VB, Italy
- Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy
| | - A Brunani
- Division of Rehabilitation Medicine, Istituto Auxologico Italiano, Ospedale S. Giuseppe, Via Cadorna 90, 28824, Piancavallo, VB, Italy
| | - B Damascelli
- Department of Interventional Radiology, EMO GVM Centro Cuore Columbus, Via Buonarroti 48, 20145, Milan, Italy
| | - V Tichà
- Radiology and Interventional Radiology Unit, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, Via Pio II 3, 20153, Milan, Italy
| | - L Castello
- Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy
| | - G Aimaretti
- Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy
| | - M Scacchi
- Division of General Medicine, IRCCS Istituto Auxologico Italiano, Ospedale S. Giuseppe, Via Cadorna 90, 28824, Piancavallo, VB, Italy
| | - P Marzullo
- Division of General Medicine, IRCCS Istituto Auxologico Italiano, Ospedale S. Giuseppe, Via Cadorna 90, 28824, Piancavallo, VB, Italy.
- Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy.
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Koklu S, Basar O, Brugge WR. Endoscopic ultrasound guided tumor directed therapy and cyst ablation. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2017. [DOI: 10.1016/j.tgie.2017.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Mukewar S, Muthusamy VR. Recent Advances in Therapeutic Endosonography for Cancer Treatment. Gastrointest Endosc Clin N Am 2017; 27:657-680. [PMID: 28918804 DOI: 10.1016/j.giec.2017.06.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Therapeutic endosonography (EUS) may play an important role in the management of cancers. EUS-guided fiducial placement has a high success rate and can aid in stereotactic radiotherapy. EUS-guided tumor ablation therapies can help in palliation of locally advanced tumors. EUS-guided antitumor injection seems to be feasible and safe in animals; initial human studies suffer from small sample size and lack of controls. Randomized, controlled trials have not shown benefit over conventional therapy. EUS celiac plexus neurolysis has gained popularity and is performed by interventional endosonographers. Large trials are needed to determine the most appropriate indications and overall usefulness of these therapies.
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Affiliation(s)
- Saurabh Mukewar
- The Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA
| | - Venkataraman Raman Muthusamy
- The Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA.
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37
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Bruno MJ. Interventional endoscopic ultrasonography: Where are we headed? Dig Endosc 2017; 29:503-511. [PMID: 28181708 DOI: 10.1111/den.12842] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 02/06/2017] [Indexed: 02/08/2023]
Abstract
Endoscopic ultrasonography (EUS) is an essential endoscopic tool within the diagnostic and therapeutic armamentarium of gastrointestinal and hepatic diseases. EUS-guided tissue acquisition will develop towards facilitating personalized treatment by obtaining large representative tissue specimens for elaborate immunohistochemical and biomolecular typing of the tumor. Intratumoral or intravascular delivery of drugs potentially offers many advantages over systemic injection. Intratumoral application of radiofrequency ablation and photodynamic therapy show promise but need to be explored further. Appositioning and connecting luminal structures within the gastrointestinal tract using fully covered expandable lumen-apposing stents will expand its indication far beyond the drainage of (infected) fluid collections and EUS-guided gastrojejunostomy is a particularly exciting development that could have significant impact on the management of gastric outlet obstruction.
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Affiliation(s)
- Marco J Bruno
- Department of Gastroenterology & Hepatology, Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Li MM, Cao J, Yang JC, Shen YJ, Cai XL, Chen YW, Qu CY, Zhang Y, Shen F, Xu LM. Effects of arginine-glycine-aspartic acid peptide-conjugated quantum dots-induced photodynamic therapy on pancreatic carcinoma in vivo. Int J Nanomedicine 2017; 12:2769-2779. [PMID: 28435257 PMCID: PMC5388266 DOI: 10.2147/ijn.s130799] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Quantum dots (QDs) conjugated with integrin antagonist arginine-glycine-aspartic acid (RGD) peptides (QDs-RGD) are novel nanomaterials with a unique optical property: a high molar extinction coefficient. Previously, we have shown that QDs-RGD demonstrate a photodynamic therapy (PDT) effect as new photosensitizers for the pancreatic cancer cell line SW1990 in vitro. Here, we investigate the application of QDs-RGD in mice bearing pancreatic tumors using PDT. To ensure that more photosensitizers accumulated in tumors, QDs-RGD were injected intratumorally. After selection of an adequate dosage for injection from analyses of biodistribution images captured by an IVIS system, PDT was initiated. Three groups were created according to different PDT procedures. In group 1, mice were injected with QDs-RGD intratumorally, and an optical fiber connected to a laser light was inserted directly into the tumor. Irradiation was sustained for 20 min with a laser light (630 nm) at 100 mW/cm2. In group 2, the laser optical fiber was placed around, and not inserted into, tumors. In group 3, PDT was conducted as in group 1 but without injection of QDs-RGD. After 28 days of observation, tumors on the back of mice in group 1 grew slowly (V/V0 =3.24±0.70) compared with the control groups, whose tumors grew quickly, and the mean V/V0 reached 6.08±0.50 (group 2) and 7.25±0.82 (group 3). Histology of tumor tissues showed more necrotic tissues, more inflammatory cells, and less vascular tissue in the PDT group than those in the control groups. These results suggest that QDs-RGD-mediated PDT, with illumination using an optical fiber inserted directly into the tumor, can inhibit the growth of SW1990 tumors with high efficiency in nude mice.
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Affiliation(s)
- Ming-Ming Li
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Jia Cao
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Jia-Chun Yang
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Yu-Jie Shen
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Xiao-Lei Cai
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Yuan-Wen Chen
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Chun-Ying Qu
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Yi Zhang
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Feng Shen
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Lei-Ming Xu
- Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China
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Abstract
Initially, endoscopic ultrasound (EUS) was developed to inspect the pancreas and other organs adjacent to the gastrointestinal tract. After introduction of curvilinear-array echoendoscopes, EUS has been used for a variety of interventions in gastroenterology, including fine needle aspiration, pancreatobiliary drainage and tumor ablation. EUS-guided ablation of pancreatic cystic tumors with ethanol and with or without cytotoxic agents has been studied, showing its potential to become an alternative to surgery. However, only few attempts at using ethanol ablation to treat solid pancreatic tumors have been reported. Recently, EUS-guided radiofrequency ablation was introduced and has been cautiously applied for pancreatic cancer. This article focuses on the clinical application of EUS for the ablation of solid pancreatic tumors.
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Affiliation(s)
- Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Wan Seo
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Signoretti M, Valente R, Repici A, Delle Fave G, Capurso G, Carrara S. Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook. World J Gastrointest Endosc 2017; 9:41-54. [PMID: 28250896 PMCID: PMC5311472 DOI: 10.4253/wjge.v9.i2.41] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 10/12/2016] [Accepted: 12/09/2016] [Indexed: 02/05/2023] Open
Abstract
Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer (LAPC), pancreatic neuroendocrine tumours (PNETs), and pancreatic cystic lesions (PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as well as hybrid cryotherm probe combining radiofrequency with cryotechnology. To date, many reports and case series have confirmed the safety and feasibility of that kind of ablation technique in the pancreatic setting. Moreover, EUS-guided fine-needle injection is emerging as a method to deliver ablative and anti-tumoral agents inside the tumuor. Ethanol injection has been proposed mostly for the treatment of PCLs and for symptomatic functioning PNETs, and the use of gemcitabine and paclitaxel is also interesting in this setting. EUS-guided injection of chemical or biological agents including mixed lymphocyte culture, oncolytic viruses, and immature dendritic cells has been investigated for the treatment of LAPC. Data on the long-term efficacy of these approaches, and large prospective randomized studies are needed to confirm the real clinical benefits of these techniques for the management of pancreatic lesions.
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Braden B, Jenssen C, D’Onofrio M, Hocke M, Will U, Möller K, Ignee A, Dong Y, Cui XW, Săftoiu A, Dietrich CF. B-mode and contrast-enhancement characteristics of small nonincidental neuroendocrine pancreatic tumors. Endosc Ultrasound 2017; 6:49-54. [PMID: 28218201 PMCID: PMC5331844 DOI: 10.4103/2303-9027.200213] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 11/02/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Imaging of the pancreas for detection of neuroendocrine tumors is indicated as surveillance in multiple endocrine neoplasia type 1 (MEN1) or if typical clinical symptoms combined with hormone production raise the suspicion of a neuroendocrine tumor. Endoscopic ultrasound (EUS) is considered the best imaging modality to detect small pancreatic tumors. However, little is known about how small pancreatic neuroendocrine tumors (pNETs) present on EUS. PATIENTS AND METHODS In this multicenter study, we retrospectively analyzed the endosonographic characteristics of small pNETs which had been detected due to typical biochemistry and clinical symptoms or during surveillance of MEN 1. Only small pancreatic tumors ≤15 mm with histological confirmation as pNET were included. B-mode and contrast-enhanced ultrasound- and EUS patterns were analyzed. RESULTS Among 32 patients with histologically proven small pNETs, 7 patients had known MEN1. Among the pNETs, 20 were insulinoma, 2 gastrinoma, 3 glucagonoma, 6 nonfunctional in MEN1, and one PPoma. 94% of the pNET appeared hypoechogenic, only 1 isoechogenic and 1 hyperechogenic. After contrast injection, 90% of the pNETS showed hyperenhancement compared to the surrounding pancreatic parenchyma. CONCLUSION The high spatial resolution of EUS allows detection and even cytological confirmation of pNET <7 mm diameter. Hypoechogenicity in B-mode and hyperenhancement after injection of contrast agents are endosonographic characteristics of small pNET and present in >90% of pNETs.
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Affiliation(s)
- Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | - Christian Jenssen
- Medical Department, Krankenhaus Maerkisch-Oderland, Strausberg, Germany
| | - Mirko D’Onofrio
- Department of Radiology, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - Michael Hocke
- Medical Department, Helios Klinikum Meiningen, Meiningen, Germany
| | - Uwe Will
- SRH Wald-Klinikum Gera, Gera, Germany
| | - Kathleen Möller
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Andre Ignee
- Medical Department, Caritas-Krankenhaus, Uhlandstr. 7 D-97980 Bad Mergentheim, Germany
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Adrian Săftoiu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Christoph F. Dietrich
- Medical Department, Caritas-Krankenhaus, Uhlandstr. 7 D-97980 Bad Mergentheim, Germany
- Sino-German Research Center of Ultrasound in Medicine, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Matsumoto K, Kato H, Tsutsumi K, Fushimi S, Iwamuro M, Oda S, Mizukawa S, Akimoto Y, Uchida D, Tomoda T, Yamamoto N, Horiguchi S, Okada H. Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model. Ecancermedicalscience 2016; 10:663. [PMID: 27594908 PMCID: PMC4990054 DOI: 10.3332/ecancer.2016.663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. METHODS Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. RESULTS Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. CONCLUSIONS Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.
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Affiliation(s)
- Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Koichiro Tsutsumi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Soichiro Fushimi
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Shinsuke Oda
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Sho Mizukawa
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Yutaka Akimoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Daisuke Uchida
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Takeshi Tomoda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Naoki Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Shigeru Horiguchi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
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