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Matsumoto K, Kato H, Itoi T, Kitano M, Hara K, Kuwatani M, Takenaka M, Ashida R, Mukai S, Okuno N, Kawakubo K, Yamazaki T, Sakurai J, Nakatsuka Y, Yoshida M, Otsuka M. Efficacy and safety of endoscopic ultrasonography-guided ethanol injections of small pancreatic neuroendocrine neoplasms: a prospective multicenter study. Endoscopy 2025; 57:321-329. [PMID: 39454635 DOI: 10.1055/a-2452-4607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2024]
Abstract
Endoscopic ultrasonography (EUS)-guided ethanol injection (EI) has recently been introduced as one of the management strategies for pancreatic neuroendocrine neoplasms (PNENs); however, its role as a surgical alternative is unclear. We evaluated the efficacy and safety of EUS-EI in treating small PNENs through a prospective multicenter study.Patients with grade 1 tumors of ≤15 mm confirmed by pathology were included. The primary end point assessed efficacy and safety, measuring complete ablation using computed tomography at 1 and 6 months, prevention of adverse events (AEs) within 1 month, severe pancreatic fistula at 1 month, and incidence/worsening of diabetes mellitus (DM) at 6 months. The composite end point of EUS-EI was compared with that of historical results of a study based on surgical treatment.25 patients with PNENs, with a median tumor size of 10.1 mm, were treated using EUS-EI. The composite primary end point was achieved by 76.0% of patients (19/25; 95%CI 54.9%-90.6%), a proportion significantly higher than that of surgical treatment (P = 0.008). Regarding efficacy, 88.0% (22/25) of patients achieved complete ablation at 1 and 6 months (95%CI 68.8%-97.5%). Regarding safety, 96.0% (24/25) of patients had no severe AEs within 1 month (95%CI 79.7%-99.9%). No patients had severe pancreatic fistulas at 1 month, and 84.0% (21/25) had no incidence or exacerbation, or both, of DM at 6 months (95%CI 63.9%-95.5%).EUS-EI is safe and could be a potent treatment option for patients with small PNENs.
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Affiliation(s)
- Kazuyuki Matsumoto
- Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Hironari Kato
- Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Takao Itoi
- Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Kazuo Hara
- Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Masaki Kuwatani
- Gastroenterology and Hepatology, Hokkaido University Hospital, Hokkaido, Japan
| | - Mamoru Takenaka
- Gastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical Sciences, Osakasayama, Japan
| | - Reiko Ashida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Shuntaro Mukai
- Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Nozomi Okuno
- Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kazumichi Kawakubo
- Gastroenterology and Hepatology, Hokkaido University Hospital, Hokkaido, Japan
| | - Tatsuhiro Yamazaki
- Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Jun Sakurai
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Yuki Nakatsuka
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Michihiro Yoshida
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Motoyuki Otsuka
- Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
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Song YJ, Lim JK, Choi JH. Role of endoscopic ultrasound in the diagnosis and local ablative therapy of pancreatic neuroendocrine tumors. Korean J Intern Med 2025; 40:170-180. [PMID: 39995262 PMCID: PMC11938681 DOI: 10.3904/kjim.2024.293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 02/26/2025] Open
Abstract
Advancements in diagnostic technology have led to the improved detection of pancreatic neuroendocrine tumors (PNETs) and thus to an increase in the number of reported cases. Endoscopic ultrasound (EUS) technology, including in combination with contrast-enhanced harmonic imaging, aids in distinguishing PNETs from other tumors, while EUS-guided fine-needle aspiration or biopsy has improved the histological diagnosis and grading of tumors. The recent introduction of EUS-guided ablation using ethanol injection or radiofrequency ablation has offered an alternative to surgery in the management of PNETs. Comparisons with surgery have shown similar outcomes but fewer adverse effects. Although standardized protocols and prospective studies with long-term follow-up are still needed, EUS-based methods are promising approaches that can contribute to a better quality of life for PNET patients.
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Affiliation(s)
- Yun Je Song
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
| | - Jun Kyeong Lim
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
| | - Jun-Ho Choi
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
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Masciangelo G, Campana D, Ricci C, Andrini E, Rakichevikj E, Fusaroli P, Lisotti A. Endoscopic Ultrasound-Guided Locoregional Treatments for Pancreatic Neuroendocrine Neoplasms. Curr Oncol 2025; 32:113. [PMID: 39996913 PMCID: PMC11854204 DOI: 10.3390/curroncol32020113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 02/09/2025] [Accepted: 02/13/2025] [Indexed: 02/26/2025] Open
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) represent approximately 2% of all solid pancreatic tumors. The incidence of pNENs has been increasing in the last decade. The clinical manifestations of pNENs range from hormone secretion syndromes in functioning neoplasms (F-pNENs) to local infiltration or distant metastases in late-stage diagnoses or incidental findings in small non-functioning neoplasms (NF-pNENs). While surgery is the gold-standard treatment for larger and more aggressive tumors, small and low-grade tumors (G1) may be followed-up due to the indolent course of disease. Recently, endoscopic ultrasound (EUS)-guided ablative techniques, such as ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA), have emerged as promising options for loco-regional ablations in selected cases. Despite promising safety profile and efficacy, high-quality evidence is needed to support their widespread adoption. This article reviews the current state of EUS-guided locoregional therapies, patient selection criteria, procedural details, and associated risks.
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Affiliation(s)
- Graziella Masciangelo
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40026 Bologna, Italy; (G.M.); (E.R.); (P.F.)
| | - Davide Campana
- Department of Medical and Surgical Sciences (DIMEC), Medical Oncology Unit, Alma Mater Studiorum-University of Bologna, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.C.); (E.A.)
| | - Claudio Ricci
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy;
| | - Elisa Andrini
- Department of Medical and Surgical Sciences (DIMEC), Medical Oncology Unit, Alma Mater Studiorum-University of Bologna, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.C.); (E.A.)
| | - Emilija Rakichevikj
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40026 Bologna, Italy; (G.M.); (E.R.); (P.F.)
| | - Pietro Fusaroli
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40026 Bologna, Italy; (G.M.); (E.R.); (P.F.)
| | - Andrea Lisotti
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40026 Bologna, Italy; (G.M.); (E.R.); (P.F.)
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Jürgensen C, Eckart M, Haberbosch L, Tacke F, Sandforth A, Birkenfeld AL, Overkamp D, Daniels M, Mogl M, Goretzki P, Strasburger C, Mai K, Spranger J, Jumpertz von Schwartzenberg R. Endoscopic ultrasound-guided ethanol ablation versus surgical resection of insulinomas. ULTRASCHALL IN DER MEDIZIN (STUTTGART, GERMANY : 1980) 2024; 45:519-527. [PMID: 37931914 DOI: 10.1055/a-2204-5814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2023]
Abstract
PURPOSE Insulinoma is a rare tumor of the pancreas that can lead to hypoglycemia. To date, the standard therapy is surgical resection. After the first case report of successful endoscopic ultrasound-guided (EUS) ethanol injection 16 years ago, the need for establishing an alternative treatment method remains unchanged given the high morbidity rates of surgery and its unsuitability in some patients. MATERIALS AND METHODS Here, we provide retrospective data from 33 insulinoma patients that were treated at our center between 2010 and 2021. Of these, 9 patients were treated with EUS-guided ethanol injection and 24 underwent pancreatic surgery. RESULTS The ethanol group was older (ethanol: mean ± SE 67.8±11.2 years vs. surgery: 52.3±15.7, p=0.014) with a higher Charlson Comorbidity Index (3.0 (1.0;4.0) vs. 1.0 (0.0;2.0), p=0.008). The lowest glucose values were similar between groups before (ethanol: 2.09±0.17 mmol/l vs. surgery: 1.81±0.08, p=0.158) and after (4.95±0.74 vs. 5.41±0.28, p=0.581) the respective treatments. Complications occurred more frequently in the surgery group (11 % vs. 54 %, p=0.026). One patient after prior partial pancreatectomy died postoperatively. The hospitalization time was significantly shorter in the ethanol group (4.78±0.78 days vs. 19.88±4.07, p<0.001). CONCLUSION EUS-guided ethanol injection can be similarly effective for the treatment of hyperinsulinemic hypoglycemia compared with pancreatic surgery but seems to be associated with less severe complications. This implies the need for prospective randomized trials in insulinoma patients with a low risk for malignancy.
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Affiliation(s)
- Christian Jürgensen
- Department of Hepatology and Gastroenterology, Charité University Medicine, Berlin, Germany
| | - Marius Eckart
- Department of Hepatology and Gastroenterology, Charité University Medicine, Berlin, Germany
| | - Linus Haberbosch
- Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Charité University Medicine, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité University Medicine, Berlin, Germany
| | - Arvid Sandforth
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, Neuherberg, Germany
| | - Andreas L Birkenfeld
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, Neuherberg, Germany
| | - Dietrich Overkamp
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Martin Daniels
- Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Charité University Medicine, Berlin, Germany
| | - Martina Mogl
- Department of Surgery, Charité University Medicine, Berlin, Germany
| | - Peter Goretzki
- Department of Surgery, Charité University Medicine, Berlin, Germany
| | - Christian Strasburger
- Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Charité University Medicine, Berlin, Germany
| | - Knut Mai
- Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Charité University Medicine, Berlin, Germany
| | - Joachim Spranger
- Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Charité University Medicine, Berlin, Germany
- Berlin Institute of Health at Charite, Berlin, Germany
| | - Reiner Jumpertz von Schwartzenberg
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, Neuherberg, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
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Ribeiro T, Castanheira-Rodrigues S, Bastos P, Cristino H, Fernandes A, Rodrigues-Pinto E, Bispo M, Rio-Tinto R, Vilas-Boas F. Portuguese Pancreatic Club Perspectives on Endoscopic Ultrasound-Guided and Surgical Treatment of Pancreatic Neuroendocrine Tumors. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:225-235. [PMID: 39022303 PMCID: PMC11250664 DOI: 10.1159/000534032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 08/11/2023] [Indexed: 07/20/2024]
Abstract
Pancreatic neuroendocrine tumors (panNETs) are a group of neoplasms with heterogenous biological and clinical phenotypes. Although historically regarded as rare, the incidence of these tumors has been increasing, mostly owing to improvements in the detection of small, asymptomatic tumors with imaging. The heterogeneity of these lesions creates significant challenges regarding diagnosis, staging, and treatment. Endoscopic ultrasound (EUS) has improved the characterization of pancreatic lesions. Furthermore, EUS nowadays has evolved from a purely diagnostic modality to allow the performance of minimally invasive locoregional therapy for pancreatic focal lesions. The choice of treatment as well as the treatment goals depend on several factors, including tumor secretory status, grading, staging, and patient performance status. Surgery has been the mainstay for the management of these patients, particularly for localized, low-grade, large panNETs >2 cm. Over the last decade, a significant body of evidence has been accumulated evaluating the role of EUS for the ablative therapy of panNETs, namely by the use of chemoablative agents and radiofrequency. Although endoscopic techniques are not routinely recommended by international guidelines, they may be considered for the treatment of smaller lesions in patients who are unwilling or unfit for pancreatic surgery. In this review, we summarize the existing evidence on the interventional techniques for the treatment of patients with panNETs, focusing on the EUS-guided and surgical approaches.
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Affiliation(s)
- Tiago Ribeiro
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | | | - Pedro Bastos
- Department of Gastroenterology, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Humberto Cristino
- Department of General Surgery, Centro Hospitalar Universitário de São João, Porto, Portugal
| | | | - Eduardo Rodrigues-Pinto
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Miguel Bispo
- Digestive Oncology Unit, Gastroenterology Department, Champalimaud Foundation, Lisbon, Portugal
| | - Ricardo Rio-Tinto
- Digestive Oncology Unit, Gastroenterology Department, Champalimaud Foundation, Lisbon, Portugal
| | - Filipe Vilas-Boas
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
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Chon HK, Kozarek RA. History of the Interventional Pancreaticobiliary Endoscopy. Gastrointest Endosc Clin N Am 2024; 34:383-403. [PMID: 38796288 DOI: 10.1016/j.giec.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2024]
Abstract
With the introduction of endoscopic retrograde cholangiopancreatography and linear endoscopic ultrasound, interventional pancreaticobiliary (PB) endoscopy has had an enormous impact in the management of pancreatic and biliary diseases. Continuous efforts to improve various devices and techniques have revolutionized these treatment modalities as viable alternatives to surgery. In recent years, trends toward combining endoscopic techniques with other modalities, such as laparoscopic and radiological interventions, for complex PB diseases have emerged using a multidisciplinary approach. Ongoing research and clinical experience will lead to refinements in interventional PB endoscopic techniques and subsequently improve outcomes and reduce complication rates.
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Affiliation(s)
- Hyung Ku Chon
- Division of Biliopancreas, Department of Internal Medicine, Wonkwang University Medical School, and Hospital, Iksan, Republic of Korea; Institution of Wonkwang Medical Science, Iksan, Republic of Korea
| | - Richard A Kozarek
- Division of Gastroenterology and Hepatology, Center for Digestive Health, Virginia Mason Franciscan Health, 1100 Ninth Avenue, Seattle, WA 98101, USA; Center for Interventional Immunology, Benaroya Research Institute, Virginia Mason Franciscan Health, 1201 Ninth Avenue, Seattle, WA 98101, USA.
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Matsumoto K, Komatsubara M, Inagaki K, Kato H, Otuka M. Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS-guided ethanol injection. Endosc Ultrasound 2024; 13:193-195. [PMID: 39318649 PMCID: PMC11419466 DOI: 10.1097/eus.0000000000000058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 03/14/2024] [Indexed: 09/26/2024] Open
Affiliation(s)
- Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | | | - Kenichi Inagaki
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Motoyuki Otuka
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
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Xiao D, Zhu L, Xiong S, Yan X, Jiang Q, Wang A, Jia Y. Outcomes of endoscopic ultrasound-guided ablation and minimally invasive surgery in the treatment of pancreatic insulinoma: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1367068. [PMID: 38645424 PMCID: PMC11026617 DOI: 10.3389/fendo.2024.1367068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 03/25/2024] [Indexed: 04/23/2024] Open
Abstract
Background and aims Most pancreatic insulinomas can be treated by minimally invasive modalities. The aim of this meta-analysis was to assess the clinical outcomes of endoscopic ultrasound (EUS)-guided ablation and minimally invasive surgery (MIS) in the treatment of pancreatic insulinoma. Materials and methods Online databases were searched for relevant studies. The primary aim was to compare the rates of adverse events (AEs) and the secondary aims were to compare the clinical and technical success rates, length of hospital stays, and symptom recurrence rates between EUS and MIS approaches. Results Eight studies with 150 patients were identified that reported EUS-guided ablation outcomes, forming the EUS group, and 9 studies with 236 patients reported MIS outcomes, forming the MIS group. The pooled median age of the included patients in the EUS group was greater than that of the MIS group (64.06 vs. 44.98 years old, p < 0.001). Also, the technical success rate was significantly higher in the EUS group (100% vs. 96.6%, p = 0.025), while the clinical success was significantly higher (6%) in the MIS group (94% vs. 98.7%, p = 0.021). The AE rates (18.7% vs. 31.1%, p = 0.012) and severe AE rates (1.3% vs. 7.9%, p = 0.011) were significantly lower in the EUS group. The median length of hospital stay in the EUS group (2.68 days, 95% CI: 1.88-3.48, I2 = 60.3%) was significantly shorter than in the MIS group (7.40 days, 95% CI: 6.22-8.58, I2 = 42.2%, p < 0.001). The recurrence rate was significantly higher in the EUS group (15.3% vs. 1.3%, p < 0.001). Conclusions EUS-guided ablation is associated with a lower AE rate and a shorter length of hospital stay, but a higher recurrence rate for the treatment of insulinoma compared with MIS. The EUS approach may be an alternative, even first-line, treatment for poor surgery candidates.
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Affiliation(s)
- Dan Xiao
- Department of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China
| | - Li Zhu
- Gastrointestinal Surgery, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China
| | - Si Xiong
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China
| | - Xu Yan
- Internal Medicine Department, University Hospital, Wuhan Institute of Technology, Wuhan, Hubei, China
| | - Qin Jiang
- Department of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China
| | - Ao Wang
- Department of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China
| | - Yegui Jia
- Department of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China
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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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Xu R, Zhang K, Ge N, Sun S. EUS-guided interventional therapies for pancreatic diseases. Front Med (Lausanne) 2024; 10:1329676. [PMID: 38259846 PMCID: PMC10801084 DOI: 10.3389/fmed.2023.1329676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 12/26/2023] [Indexed: 01/24/2024] Open
Abstract
Endoscopic ultrasound (EUS) is an integrated diagnostic technique merging endoscope and ultrasound to examine the digestive system. EUS has emerged as a primary diagnostic method for pancreatic diseases due to its distinctive benefits. Over the past four decades, EUS has undergone a transformation, shifting its role from primarily diagnostic to increasingly therapeutic. Additionally, in recent years, EUS has emerged as an increasingly prominent adjunctive or alternative approach to conventional surgical interventions. This review provides a comprehensive analysis of current technological approaches in the treatment of pancreatic diseases. The dynamic interplay with diverse therapeutic approaches has reinvigorated EUS and shaped its trajectory in the management of pancreatic diseases.
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Affiliation(s)
| | | | | | - Siyu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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Nakai Y. Endoscopic Ultrasound-Guided Antitumor Therapy. Gastrointest Endosc Clin N Am 2024; 34:79-89. [PMID: 37973232 DOI: 10.1016/j.giec.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
Endoscopic ultrasound (EUS) has been used for various interventions to manage intra-abdominal lesions. EUS-guided antitumor therapy via delivery of chemotherapeutic agents, energy, and radioactive seeds has advantages of less invasiveness than surgical approaches, and the anatomic proximity allows easy and accurate access to the pancreas. The feasibility of EUS-guided antitumor therapy has been reported both in pancreatic solid and cystic neoplasms, with promising preliminary results. Randomized controlled trials are mandatory to further confirm its role.
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Affiliation(s)
- Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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Silva MA, Ruge A, Vicente N, Fernandes A, Pereira E, Vasconcelos H. Pancreatic Insulinoma: When Surgery Is Not an Option. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2023; 30:451-454. [PMID: 38476152 PMCID: PMC10928855 DOI: 10.1159/000527034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/22/2022] [Indexed: 03/14/2024]
Affiliation(s)
- Maria Azevedo Silva
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - André Ruge
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Nuno Vicente
- Department of Endocrinology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Alexandra Fernandes
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Eduardo Pereira
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
- Department of Gastroenterology, Hospital Amato Lusitano, Castelo Branco, Portugal
| | - Helena Vasconcelos
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
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13
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Prete AM, Gonda TA. Endoscopic Ultrasound-Guided Local Ablative Therapies for the Treatment of Pancreatic Neuroendocrine Tumors and Cystic Lesions: A Review of the Current Literature. J Clin Med 2023; 12:jcm12093325. [PMID: 37176764 PMCID: PMC10179349 DOI: 10.3390/jcm12093325] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/02/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023] Open
Abstract
Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.
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Affiliation(s)
- Alexander M Prete
- Department of Medicine, New York University (NYU) Grossman School of Medicine, New York, NY 10016, USA
| | - Tamas A Gonda
- Division of Gastroenterology and Hepatology, New York University (NYU) Langone Health, New York, NY 10016, USA
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14
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Rimbaş M, Rizzatti G, Tosoni A, Impagnatiello M, Panzuto F, Larghi A. Small nonfunctional pancreatic neuroendocrine neoplasms: Time for a step-up treatment approach? Endosc Ultrasound 2023; 12:1-7. [PMID: 36510866 PMCID: PMC10134916 DOI: 10.4103/eus-d-22-00028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Surgery has been regarded as the only curative treatment for patients with small nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) less than 2 cm. Due to the significant adverse event rates of surgery, the European Neuroendocrine Tumor Society issued guidelines favoring surveillance for those patients lacking criteria suggestive of an aggressive disease. Despite the above recommendations, a significant proportion of small NF-PNEN patients still undergo surgery. Recently, several studies have reported the safety and effectiveness of EUS-guided radiofrequency ablation (RFA) for the treatment of small NF-PNENs. The experience with EUS-RFA is, however, limited, but published results indicate a potential role as a minimally invasive alternative treatment for these patients, in particular in those in whom further progression is more probable, before they reach the absolute need for surgery. A step-up approach with EUS-RFA followed by surgery for the failure cases can become a valid option to be validated in clinical studies.
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Affiliation(s)
- Mihai Rimbaş
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Gastroenterology, Colentina Clinical Hospital; Department of Internal Medicine, Carol Davila University of Medicine, Bucharest, Romania
| | - Gianenerico Rizzatti
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alberto Tosoni
- Department of Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Michele Impagnatiello
- Department of Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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15
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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: 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: 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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16
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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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17
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Iabichino G, Di Leo M, Arena M, Rubis Passoni GG, Morandi E, Turpini F, Viaggi P, Luigiano C, De Luca L. Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:4943-4958. [PMID: 36160644 PMCID: PMC9494936 DOI: 10.3748/wjg.v28.i34.4943] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/29/2022] [Accepted: 08/22/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
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Affiliation(s)
| | - Milena Di Leo
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Monica Arena
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | | | | | - Francesca Turpini
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Paolo Viaggi
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Carmelo Luigiano
- Gastroenterology Section, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria 89124, Italy
| | - Luca De Luca
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
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18
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Ehlken H, Younis F, Wolter S, Schrader J. Spannungsfeld endoskopische Resektionsverfahren bei GEP-NET // Endoscopic resection for GEP-NET. Zentralbl Chir 2022; 147:256-263. [PMID: 35705087 DOI: 10.1055/a-1829-7370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ZusammenfassungNeuroendokrine Tumoren des Verdauungstraktes (GEP-NET) sind eine seltene Tumorentität, die häufig als Zufallsbefund diagnostiziert werden. Ein großer Teil dieser Zufallsdiagnosen wird im
Rahmen einer endoskopischen Untersuchung gestellt. Während die vollständige Entfernung des Tumors im Sinne einer kurativen chirurgischen Resektion nach onkologischen Kriterien das
Standardvorgehen für lokalisierte Tumorerkrankungen ist, kann bei kleinen Tumoren ohne Hinweis und Risiko für eine lymphogene Metastasierung eine endoskopische Abtragung in gleicher
Intention erfolgen. Während dies für Magen-, Duodenum- und Rektum-NET der Standard ist, sollten NET des Jejunums und Ileums aufgrund der hohen Metastasierungsrate trotz geringer Tumorgröße
regelhaft nicht endoskopisch angegangen werden. Die Grenze für eine endoskopische Resektion ergibt sich sowohl durch die technische Machbarkeit im Sinne des Erreichens einer R0-Resektion,
der erwarteten Komplikationen im Sinne von Blutung und Perforationen als auch durch das vermutete Risiko für eine lymphogene Metastasierung. Generell wird eine endoskopische Resektion bei
Befunden < 1 cm regelhaft empfohlen, da sowohl die gute technische Machbarkeit als auch das geringe Metastasierungsrisiko für eine endoskopische Resektion sprechen. Bei allen Befunden
über 2 cm Größe sind sowohl die technischen Erfolgsaussichten so niedrig als auch das Metastasierungsrisiko so hoch, dass in dieser Situation regelhaft ein chirurgisches Vorgehen erfolgen
sollte. Es bleibt somit ein Graubereich bei der Tumorgröße zwischen 1 und 2 cm, wo sowohl endoskopische, aber auch chirurgische Resektionsverfahren sinnvoll eingesetzt werden können.
Zunehmend kommen auch gemeinsame Eingriffe im Sinne eines endoskopisch-laparoskopischen Rendezvous-Verfahrens zum Einsatz – insbesondere im Duodenum bieten sich diese Eingriffe an, um eine
minimale Resektion mit größtmöglicher R0-Erfolgsrate und niedriger Perforationsrate zu erreichen.
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Affiliation(s)
- Hanno Ehlken
- Klinik und Poliklinik für interdisziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Fadi Younis
- Klinik und Poliklinik für interdisziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Stefan Wolter
- Klinik für Allgemein-, Viszeral und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Jörg Schrader
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
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19
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Ong AS, Wang L, Aw J. Lesson of the month: Recurrent falls and hypoglycaemia in an older woman. Clin Med (Lond) 2022; 22:90-91. [PMID: 38589109 DOI: 10.7861/clinmed.2021-0671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
We present a case of a non-diabetic 84-year-old woman who presented with recurrent falls and hypoglycaemic episodes and was subsequently diagnosed to have a solitary insulinoma. Her multiple fall episodes may have been precipitated by her low blood glucose levels. We discuss the clinical and radiological findings of insulinoma.
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Affiliation(s)
| | - Lin Wang
- Outram Community Hospital, Singapore
| | - Junjie Aw
- Outram Community Hospital, Singapore; clinical instructor, DUKE-NUS Medical School, Singapore and clinical physician faculty member, SingHealth, Singapore
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20
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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] [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
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21
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Mueller JL, Morhard R, DeSoto M, Chelales E, Yang J, Nief C, Crouch B, Everitt J, Previs R, Katz D, Ramanujam N. Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia. Sci Rep 2021; 11:16869. [PMID: 34413378 PMCID: PMC8376953 DOI: 10.1038/s41598-021-96223-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 08/05/2021] [Indexed: 11/08/2022] Open
Abstract
In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue. Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.
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Affiliation(s)
- Jenna L Mueller
- Department of Bioengineering, University of Maryland, 3102 A. James Clark Hall, 8278 Paint Branch Drive, College Park, MD, 20742, USA.
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
| | - Robert Morhard
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Michael DeSoto
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Erika Chelales
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Jeffrey Yang
- Department of Bioengineering, University of Maryland, 3102 A. James Clark Hall, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Corrine Nief
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Brian Crouch
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Jeffrey Everitt
- Department of Pathology, Duke University School of Medicine, Durham, NC, USA
| | - Rebecca Previs
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA
| | - David Katz
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA
| | - Nimmi Ramanujam
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
- Duke Global Health Institute, Duke University, Durham, NC, USA
- Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
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22
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Matsumoto K, Kato H, Kitano M, Hara K, Kuwatani M, Ashida R, Takenaka M, Yamazaki T, Sakurai J, Yoshida M, Okada H. Study protocol for endoscopic ultrasonography-guided ethanol injection therapy for patients with pancreatic neuroendocrine neoplasm: a multicentre prospective study. BMJ Open 2021; 11:e046505. [PMID: 34253667 PMCID: PMC8276291 DOI: 10.1136/bmjopen-2020-046505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION The management of small pancreatic neuroendocrine neoplasms (PNENs) remains controversial. The standard treatment for PNENs is surgical resection; however, invasiveness of surgical procedure remains higher and the incidence of postoperative adverse events is still high. Recently, the efficacy and safety of endoscopic ultrasonography (EUS)-guided ethanol injection for small PNENs has been preliminarily demonstrated. Thus, a multicentre prospective study is being conducted to evaluate the efficacy and safety of EUS-guided ethanol injection therapy for small PNENs. METHODS AND ANALYSIS The major eligibility criteria are the presence of pathologically diagnosed grade (G) 1 tumour, a tumour size of ≤15 mm and non-functional PNEN or insulinoma. For treatment, we will use a 25-gauge needle and pure ethanol. Contrast-enhanced CT (CE-CT) will be performed on postoperative day 3-5, and if enhanced areas of the tumour are still apparent, an additional session is scheduled during the same hospitalisation period. We set the total amount of ethanol per session to 2 mL. To evaluate the efficacy and safety, CE-CT will be performed at 1 and 6 months after treatment. The primary endpoint is the percentage of subjects who achieved all of the following evaluated points. Efficacy will be evaluated based on the achievement of complete ablation (defined as no enhanced area within the tumour on CE-CT) at 1 and 6 months. Safety will be evaluated based on the avoidance of severe adverse events within 1 month after treatment, continuing severe pancreatic fistula at 1 month after treatment and the incidence and/or exacerbation of diabetes mellitus at 6 months after treatment. ETHICS AND DISSEMINATION This protocol has been approved by Okayama University Certified Review Board (approval number. CRB19-007). The results will be submitted to peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER jRCTs061200016.
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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
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Kazuo Hara
- Gastroenterology, Aichi Cancer Center, Nagoya, Japan
| | - Masaki Kuwatani
- Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Reiko Ashida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Kindai University, Osaka-Sayama, Japan
| | - Tatsuhiro Yamazaki
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Jun Sakurai
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Michihiro Yoshida
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
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23
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Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms. J Clin Med 2021; 10:jcm10122638. [PMID: 34203922 PMCID: PMC8232656 DOI: 10.3390/jcm10122638] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/28/2021] [Accepted: 06/07/2021] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.
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24
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Keutgen XM, Ornell KJ, Vogle A, Lakiza O, Williams J, Miller P, Mistretta KS, Setia N, Weichselbaum RR, Coburn JM. Sunitinib-Loaded Chondroitin Sulfate Hydrogels as a Novel Drug-Delivery Mechanism for the Treatment of Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2021; 28:8532-8543. [PMID: 34091777 DOI: 10.1245/s10434-021-10245-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 05/20/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PanNETs) are increasingly common. Experts debate whether small tumors should be resected. Tumor destruction via injection of cytotoxic agents could offer a minimal invasive approach to this controversy. We hypothesize that a new drug delivery system comprising chondroitin sulfate (CS) hydrogels loaded with sunitinib (SUN) suppresses tumor growth in PanNET cells. METHODS Injectable hydrogels composed of CS modified with methacrylate groups (MA) were fabricated and loaded with SUN. Loading target was either 200 µg (SUN200-G) or 500 µg (SUN500-G) as well as sham hydrogel with no drug loading (SUN0-G). SUN release from hydrogels was monitored in vitro over time and cytotoxicity induced by the released SUN was evaluated using QGP-1 and BON1 PanNET cell lines. QGP-1 xenografts were developed in 35 mice and directly injected with 25 µL of either SUN200-G, SUN500-G, SUN0-G, 100 µL of Sunitinib Malate (SUN-inj), or given 40 mg/kg/day oral sunitinib (SUN-oral). RESULTS SUN-loaded CSMA hydrogel retained complete in vitro cytotoxicity toward the QGP-1 PanNET and BON-1 PanNET cell lines for 21 days. Mouse xenograft models with QGP-1 PanNETs showed a significant delay in tumor growth in the SUN200/500-G, SUN-inj and SUN-oral groups compared with SUN0-G (p = 0.0014). SUN500-G hydrogels induced significantly more tumor necrosis than SUN0-G (p = 0.04). There was no difference in tumor growth delay between SUN200/500G, SUN-inj, and SUN-oral. CONCLUSIONS This study demonstrates that CSMA hydrogels loaded with SUN suppress PanNETs growth. This drug delivery could approach represents a novel way to treat PanNETs and other neoplasms via intratumoral injection.
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Affiliation(s)
- Xavier M Keutgen
- Endocrine Surgery Research Program, Division of General Surgery and Surgical Oncology, Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA.
| | - Kimberly J Ornell
- Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Alyx Vogle
- Endocrine Surgery Research Program, Division of General Surgery and Surgical Oncology, Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA
| | - Olga Lakiza
- Endocrine Surgery Research Program, Division of General Surgery and Surgical Oncology, Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA
| | - Jelani Williams
- Endocrine Surgery Research Program, Division of General Surgery and Surgical Oncology, Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA
| | - Paul Miller
- Endocrine Surgery Research Program, Division of General Surgery and Surgical Oncology, Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA
| | | | - Namrata Setia
- Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
| | - Ralph R Weichselbaum
- Department of Radiation Oncology and Cellular Biology, The University of Chicago Medicine, Chicago, IL, USA
| | - Jeannine M Coburn
- Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
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25
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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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26
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Insulinoma: A Recurrent Pancreatic Tumor Amendable to Computed Tomography-Guided Ethanol-Lipiodol Injection. ACG Case Rep J 2021; 8:e00539. [PMID: 33654702 PMCID: PMC7909311 DOI: 10.14309/crj.0000000000000539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 09/04/2020] [Indexed: 11/28/2022] Open
Abstract
Insulinomas are rare, with an annual incidence of 1–4 people per mission. Insulinomas are the most common functioning endocrine neoplams of the pancreas. Endoscopic ultrasound has both diagnostic and therapeutic yield in undifferentiated pancreatic tumors. We present a case of a recurrent insulinoma, refractory to surgical and medical management diagnosed with endoscopic ultrasound. Our case uniquely conveys a successful, alternative approach to addressing symptomatic insulinomas refractory to surgical or medical management through computed tomography–guided percutaneous ethanol-lipiodol injection.
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27
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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: 10] [Impact Index Per Article: 2.5] [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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28
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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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29
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Wang M, Vasey Q, Varikatt W, Mclean M. Ectopic insulin secretion by a large-cell neuroendocrine carcinoma of the cervix. Clin Case Rep 2021; 9:482-486. [PMID: 33505694 PMCID: PMC7813122 DOI: 10.1002/ccr3.3562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 10/31/2020] [Accepted: 11/02/2020] [Indexed: 11/08/2022] Open
Abstract
In patients presenting with hyperinsulinemic hypoglycemia with a nonpancreatic neuroendocrine tumor, the diagnosis of an ectopic insulin-secreting tumor should be considered, and investigated further with confirmatory insulin staining.
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Affiliation(s)
- Mawson Wang
- Department of EndocrinologyBlacktown HospitalSydneyNSWAustralia
- Blacktown Clinical SchoolSchool of MedicineWestern Sydney UniversitySydneyNSWAustralia
| | - Quinlan Vasey
- Department of EndocrinologyBlacktown HospitalSydneyNSWAustralia
| | - Winny Varikatt
- ICPMR (Institute of Clinical Pathology and Medical Research)Westmead HospitalSydneyNSWAustralia
- Westmead Clinical SchoolUniversity of Sydney Medical SchoolSydneyNSWAustralia
| | - Mark Mclean
- Department of EndocrinologyBlacktown HospitalSydneyNSWAustralia
- Blacktown Clinical SchoolSchool of MedicineWestern Sydney UniversitySydneyNSWAustralia
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30
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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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31
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So H, Oh D, Seo DW. Recent developments in endoscopic ultrasound-guided ablation treatment. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2020. [DOI: 10.18528/ijgii200036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Hoonsub So
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Dongwook Oh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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32
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Khanna L, Prasad SR, Sunnapwar A, Kondapaneni S, Dasyam A, Tammisetti VS, Salman U, Nazarullah A, Katabathina VS. Pancreatic Neuroendocrine Neoplasms: 2020 Update on Pathologic and Imaging Findings and Classification. Radiographics 2020; 40:1240-1262. [PMID: 32795239 DOI: 10.1148/rg.2020200025] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show characteristic clinical, histomorphologic, and prognostic features; genetic alterations; and biologic behavior. Up to 10% of panNENs develop in patients with syndromes that predispose them to cancer, such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, tuberous sclerosis complex, neurofibromatosis type 1, and glucagon cell adenomatosis. PanNENs are classified as either functioning tumors, which manifest early because of clinical symptoms related to increased hormone production, or nonfunctioning tumors, which often manifest late because of mass effect. PanNENs are histopathologically classified as well-differentiated pancreatic neuroendocrine tumors (panNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (panNECs) according to the 2010 World Health Organization (WHO) classification system. Recent advances in cytogenetics and molecular biology have shown substantial heterogeneity in panNECs, and a new tumor subtype, well-differentiated, high-grade panNET, has been introduced. High-grade panNETs and panNECs are two distinct entities with different pathogenesis, clinical features, imaging findings, treatment options, and prognoses. The 2017 WHO classification system and the eighth edition of the American Joint Committee on Cancer staging system include substantial changes. Multidetector CT, MRI, and endoscopic US help in anatomic localization of the primary tumor, local-regional spread, and metastases. Somatostatin receptor scintigraphy and fluorine 18-fluorodeoxyglucose PET/CT are helpful for functional and metabolic assessment. Knowledge of recent updates in the pathogenesis, classification, and staging of panNENs and familiarity with their imaging findings allow optimal patient treatment. ©RSNA, 2020.
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Affiliation(s)
- Lokesh Khanna
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Srinivasa R Prasad
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Abhijit Sunnapwar
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Sainath Kondapaneni
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Anil Dasyam
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Varaha S Tammisetti
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Umber Salman
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Alia Nazarullah
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Venkata S Katabathina
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
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33
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Morhard R, Mueller JL, Tang Q, Nief C, Chelales E, Lam CT, Alvarez DA, Rubinstein M, Katz DF, Ramanujam N. Understanding Factors Governing Distribution Volume of Ethyl Cellulose-Ethanol to Optimize Ablative Therapy in the Liver. IEEE Trans Biomed Eng 2020; 67:2337-2348. [PMID: 31841399 PMCID: PMC7295656 DOI: 10.1109/tbme.2019.2960049] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Ethanol ablation, the injection of ethanol to induce necrosis, was originally used to treat hepatocellular carcinoma, with survival rates comparable to surgery. However, efficacy is limited due to leakage into surrounding tissue. To reduce leakage, we previously reported incorporating ethyl cellulose (EC) with ethanol as this mixture forms a gel when injected into tissue. To further develop EC-ethanol injection as an ablative therapy, the present study evaluates the extent to which salient injection parameters govern the injected fluid distribution. METHODS Utilizing ex vivo swine liver, injection parameters (infusion rate, EC%, infusion volume) were examined with fluorescein added to each solution. After injection, tissue samples were frozen, sectioned, and imaged. RESULTS While leakage was higher for ethanol and 3%EC-ethanol at a rate of 10 mL/hr compared to 1 mL/hr, leakage remained low for 6%EC-ethanol regardless of infusion rate. The impact of infusion volume and pressure were also investigated first in tissue-mimicking surrogates and then in tissue. Results indicated that there is a critical infusion pressure beyond which crack formation occurs leading to fluid leakage. At a rate of 10 mL/hr, a volume of 50 μL remained below the critical pressure. CONCLUSIONS Although increasing the infusion rate increases stress on the tissue and the risk of crack formation, injections of 6%EC-ethanol were localized regardless of infusion rate. To further limit leakage, multiple low-volume infusions may be employed. SIGNIFICANCE These results, and the experimental framework developed to obtain them, can inform optimizing EC-ethanol to treat a range of medical conditions.
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34
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Affiliation(s)
- Reiko Ashida
- Departments of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
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35
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Matsumoto K, Kato H, Kawano S, Fujiwara H, Nishida K, Harada R, Fujii M, Yoshida R, Umeda Y, Hinotsu S, Yagi T, Okada H. Efficacy and safety of scheduled early endoscopic ultrasonography-guided ethanol reinjection for patients with pancreatic neuroendocrine tumors: Prospective pilot study. Dig Endosc 2020; 32:425-430. [PMID: 31580507 DOI: 10.1111/den.13552] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 09/29/2019] [Indexed: 12/13/2022]
Abstract
Endoscopic ultrasonography (EUS)-guided ethanol injection was recently proposed for treatment of patients with small pancreatic neuroendocrine tumors (p-NET); however, tips on how to carry out safe and effective procedures are unclear. We launched a pilot study for scheduled early EUS-guided ethanol reinjection for small p-NET. Major eligibility criteria were presence of pathologically diagnosed grade (G) 1 or G2, tumor size ≤2 cm and being a poor or rejected candidate for surgery. For the treatment, we used a 25-gauge needle and pure ethanol. Contrast-enhanced computed tomography (CE-CT) was carried out on postoperative day 3, and if enhanced areas of the tumor were still apparent, an additional session was scheduled during the same hospitalization period. Primary endpoint was complete ablation rate at 1 month after treatment, and secondary endpoint was procedure-related adverse events. A total of five patients were treated. Median size of the tumor was 10 (range: 7-14) mm. Of the five patients, three underwent an additional session. Median volume of ethanol injection per session was 0.8 (range: 0.3-1.0) mL, and the total was 1.0 (0.9-1.8) mL. Complete ablation was achieved in four of the five tumors (80%) with no adverse events. During 1 year of follow up, none of the patients reported any procedure-related adverse events, and no recurrence of tumor. Scheduled early EUS-guided ethanol reinjection appears to be safe and effective for treating small p-NET (UMIN number: 000018834).
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Affiliation(s)
- Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyasu Fujiwara
- Department of Radiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Kenji Nishida
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Ryo Harada
- Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Masakuni Fujii
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Ryuichi Yoshida
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yuzo Umeda
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Shiro Hinotsu
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Takahito Yagi
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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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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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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Gao L, Natov NS, Daly KP, Masud F, Chaudhry S, Sterling MJ, Saif MW. An update on the management of pancreatic neuroendocrine tumors. Anticancer Drugs 2019; 29:597-612. [PMID: 29782352 DOI: 10.1097/cad.0000000000000633] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are a rare and heterogeneous group of neoplasia and differ in their clinical presentation, behavior, and prognosis based on both histological features and cancer stage at the time of diagnosis. Although small-sized tumors can be surgically resected, locally advanced and metastatic tumors confer a poor prognosis. In addition, only limited treatment options are available to the latter group of patients with PNETs, such as hormonal analogs, cytotoxic agents, and targeted therapy. In selected patients, liver-directed therapies are also used. As expected, clinicians taking care of these patients are challenged to develop an effective and comprehensive treatment strategy for their patients amid a wide variety of treatment modalities. Targeted therapy for PNETs is limited to sunitinib and everolimus. Presently, a number of clinical studies are ongoing to assess the efficacy of newer targeted agents alone and in combination with previous agents for the treatment of advanced PNETs. The authors reviewed the current treatment and also discussed the emerging agents and emphasized the need to identify biomarkers.
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Affiliation(s)
- Limin Gao
- Division of Hematology and Oncology, GI Oncology Program and Experimental Therapeutics
| | - Nikola S Natov
- Division of Gastroenterology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | | | | | - Sadia Chaudhry
- Foundation University Medical College, Rawalpindi, Pakistan
| | - Mark J Sterling
- Division of Gastroenterology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Muhammad W Saif
- Division of Hematology and Oncology, GI Oncology Program and Experimental Therapeutics
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Refractory Metastatic Insulinoma Treated with Everolimus, Complicated by Cryptogenic Organizing Pneumonia. AMERICAN JOURNAL OF MEDICAL CASE REPORTS 2019; 7:125-132. [PMID: 31414042 PMCID: PMC6693857 DOI: 10.12691/ajmcr-7-7-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Insulinoma is a rare neuroendocrine pancreatic islet cell tumor of which the majority are benign and solitary. Its estimated incidence is 2 to 4 cases per 1 million person-years. We report the case of an 82-year-old female who presented with metastatic insulinoma to the liver and retroperitoneal lymph nodes. It was diagnosed based on positive Whipple's triad, elevated insulin, elevated C-peptide, and negative insulin auto-antibody. Her disease was initially managed with diazoxide 100 mg orally every 8 hours, octreotide LAR 30 mg intramuscularly every month, and sunitinib 12.5 mg orally three times a day. However, patient had recurrent symptoms and imaging consistent with worsened metastatic insulinoma; and thus, treatment was changed to everolimus 10 mg PO daily. Over the subsequent 10 months, the patient developed progressive shortness of breath and hypoxemia with and oxygen saturation (SpO2) of 89% on room air. Computerized tomography (CT) and lung biopsy were consistent with cryptogenic organizing pneumonia (COP) temporally associated with the initiation of everolimus. She was started on prednisone 1 mg/kg/day and within 48 hours, her symptoms and hypoxemia improved to SpO2 of 98-99% at room air and her repeat CT chest showed marked disease improvement. Given her good response with everolimus, it was continued in conjunction with the prednisone and to this day, patient has had a significant therapeutic response with normoglycemia and stable, well-controlled symptoms. This case is unique because to our knowledge, it is the first reported case of a patient with metastatic insulinoma complicated by the development of cryptogenic organizing pneumonia. It reaffirms the causal association between everolimus and cryptogenic organizing pneumonia that has been reported numerous times in literature. However, there has been no reported cases showing that the COP can be managed with prednisone concurrently with everolimus for the metastatic insulinoma without diminished clinical benefit. While pulmonary complications have been cited as reasons for discontinuation of everolimus therapy, our case report highlights the use of steroids as a viable therapeutic strategy that allows successful therapy with everolimus to be continued. In addition to presenting this case, we will also do a thorough review of the literature surrounding the available therapeutic options of metastatic insulinoma. This will include surgery, somatostatin analogs, antimicrobials, potassium channel activators, VEGF-A inhibitors, alkylating agents and mTOR inhibitors to provide a more in-depth picture of how we treat metastatic insulinoma.
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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: 30] [Impact Index Per Article: 4.3] [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] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [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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Antitumor Activity of Intratumoral Ethanol Injection in an Orthotopic Pancreatic Cancer Cell Mouse Xenograft Model. Gastroenterol Res Pract 2018; 2018:7149565. [PMID: 29675041 PMCID: PMC5841100 DOI: 10.1155/2018/7149565] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 01/16/2018] [Accepted: 01/22/2018] [Indexed: 01/01/2023] Open
Abstract
Purpose Pancreatic cancer is a lethal disease and usually is diagnosed at advanced stages of disease. This study assessed the effects of intratumoral ethanol injection using an endoscopic ultrasound (EUS) probe on the control of pancreatic cancer in a mouse orthotopic xenograft model. Materials and Methods The subcutaneous and orthotopic human pancreatic cancer cell mouse xenograft models were established. Different concentrations of ethanol (0–95%) were injected into subcutaneous xenograft tumors. In the orthotopic tumor model, ethanol was injected into the tumor lesions under the guidance of a high-frequency EUS probe. Tumor volume, relative tumor volume (RTV), and histopathology were evaluated. The serum amylase level was analyzed at baseline and 24 h after treatment in the orthotopic tumor model. Results Injection of 40–95% ethanol induced tumor necrosis in the subcutaneous tumor model, while there was no statistical difference between the RTVs of the two groups (P = 0.81). In the orthotopic tumor model, the RTV of the 80% ethanol treatment group was less than that of the saline injection group (P < 0.01); and histologically, there was a large area of necrosis observed in the 80% ethanol group. The serum amylase level was slightly elevated at 24 h after injection and returned to the baseline level at 7 days. Conclusion Injection of 80% ethanol into xenograft tumor lesions of orthotopic pancreatic cancer resulted in tumor necrosis, and the procedure was safe and effective. Future studies will further confirm its antitumor activity as well as assess its safety and feasibility.
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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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Zilli A, Arcidiacono PG, Conte D, Massironi S. Clinical impact of endoscopic ultrasonography on the management of neuroendocrine tumors: lights and shadows. Dig Liver Dis 2018; 50:6-14. [PMID: 29102525 DOI: 10.1016/j.dld.2017.10.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 10/04/2017] [Accepted: 10/09/2017] [Indexed: 02/07/2023]
Abstract
The incidence of gastroenteropancreatic neuroendocrine neoplasms has increased in the recent decades. An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published mostly between year 1997 and June 2017, using both medical subject heading (MeSH) terms and free-language keywords about the accuracy and diagnostic and therapeutic role of endoscopic ultrasound in the context of gastro-entero-pancreatic neuroendocrine neoplasms. Endoscopic ultrasound is the modality of choice for diagnosing pancreatic neuroendocrine neoplasms and for the locoregional staging of gastric, duodenal, pancreatic and rectal neuroendocrine neoplasms; in particular, in the setting of pancreatic neuroendocrine neoplasms it has demonstrated higher accuracy in tumor detection than other imaging modalities. Furthermore, the possibility of tattooing pancreatic lesions by endoscopic ultrasound fine needle aspiration may help surgeons to locate the tumor and avoid any demolition surgery. Finally, endoscopic ultrasound-guided therapies have been proposed and used in several studies for patients unsuitable for surgery, with good results on the control of symptoms and the reduction of tumor burden.
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Affiliation(s)
- Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translatiinal and Clinical Research Center, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
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Hocke M, Braden B, Jenssen C, Dietrich CF. Present status and perspectives of endosonography 2017 in gastroenterology. Korean J Intern Med 2018; 33:36-63. [PMID: 29161800 PMCID: PMC5768548 DOI: 10.3904/kjim.2017.212] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 06/16/2017] [Indexed: 12/13/2022] Open
Abstract
Endoscopic ultrasound has become an essential tool in modern gastroenterology and abdominal surgery. Compared with all other endoscopic methods, it has the most potential for innovation and its future looks bright. Thus, we compiled this summary of established and novel applications of endoscopic ultrasound methods to inform the reader about what is already possible and where future developments will lead in improving patient care further. This review is structured in four parts. The first section reports on developments in diagnostic endoscopic ultrasound, the second looks at semi-invasive endoscopic ultrasound, and the third discusses advances in therapeutic endoscopic ultrasound. An overview on the future prospects of endoscopic ultrasound methods concludes this article.
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Affiliation(s)
- Michael Hocke
- Internal Medicine II, Helios Hospital Meiningen, Germany
| | - Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | | | - Christoph F. Dietrich
- Medical Department 2, Caritas Hospital Bad Mergentheim, Bad Mergentheim, Germany
- Correspondence to Christoph F. Dietrich, M.D. Medical Department 2, Caritas Hospital Bad Mergentheim, Uhlandstraße 7, Bad Mergentheim 97980, Germany Tel: +49-7931-582201 Fax: +49-7931-582290 E-mail:
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Lakhtakia S. Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including Ethanol and Radiofrequency Ablation. Clin Endosc 2017; 50:546-551. [PMID: 29207860 PMCID: PMC5719904 DOI: 10.5946/ce.2017.167] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Revised: 11/15/2017] [Accepted: 11/16/2017] [Indexed: 12/17/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are increasingly being detected, though usually as incidental findings. Majority of the PNETs are non-functional and surgical resection is the standard of care for most of them. However, in patients with small PNETs localized within the pancreas, who are unfit or unwilling for surgery, alternate methods of treatment are needed. Direct methods of ablation of PNETs, using either ethanol injection or radiofrequency ablation (RFA), are emerging as effective methods. The limited literature available as case reports or case series on endoscopic ultrasound (EUS)-guided local ablation using either ethanol or RFA has demonstrated safety and efficacy along with short- to medium-term sustained relief. Long-term benefits with these local ablative therapies are awaited. Comparative studies are needed to show which of these two competing technologies is superior. Finally, comparative trials of EUS-guided ablation with surgical resection in terms of efficacy and safety will ensure their place in the management algorithm.
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Affiliation(s)
- Sundeep Lakhtakia
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
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48
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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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Development of enhanced ethanol ablation as an alternative to surgery in treatment of superficial solid tumors. Sci Rep 2017; 7:8750. [PMID: 28821832 PMCID: PMC5562881 DOI: 10.1038/s41598-017-09371-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 07/27/2017] [Indexed: 12/11/2022] Open
Abstract
While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability. To address these limitations, we investigated an enhanced ethanol ablation strategy to retain ethanol within the tumor through the addition of ethyl cellulose. This increases the viscosity of injected ethanol and forms an ethanol-based gel-phase upon exposure to the aqueous tumor environment. This technique was first optimized to maximize distribution volume, using tissue-simulating phantoms. Then, chemically-induced epithelial tumors in the hamster cheek pouch were treated. As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively. In contrast, ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors. These results contribute to proof-of-concept for enhanced ethanol ablation as a novel and effective alternative to surgery for tumor treatment, with relevance to resource-limited settings.
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