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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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Alférez MD, Corda A, de Blas I, Gago L, Fernandes T, Rodríguez-Piza I, Balañá B, Corda F, Gómez Ochoa P. Percutaneous Ultrasound-Guided Radiofrequency Ablation as a Therapeutic Approach for the Management of Insulinomas and Associated Metastases in Dogs. Animals (Basel) 2024; 14:3301. [PMID: 39595353 PMCID: PMC11591051 DOI: 10.3390/ani14223301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/11/2024] [Accepted: 11/13/2024] [Indexed: 11/28/2024] Open
Abstract
Insulinomas are the most common neoplasms of the endocrine pancreas in dogs, leading to persistent hypoglycemia due to inappropriate insulin secretion. The standard treatment is surgical resection, but it carries significant risks, including pancreatitis and diabetes mellitus. This study investigates the efficacy and safety of percutaneous ultrasound-guided radiofrequency ablation (RFA) as an alternative to surgery. A total of 29 dogs diagnosed with insulinoma were treated with RFA, targeting both primary pancreatic tumors and metastases in regional lymph nodes or the liver. Blood glucose levels and tumor size were monitored before and after the procedure. RFA led to a significant increase in blood glucose levels and a reduction in tumor size in all patients, with minimal postoperative complications. The results suggest that RFA is a feasible and effective treatment option for insulinomas in dogs.
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Affiliation(s)
| | - Andrea Corda
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy;
| | - Ignacio de Blas
- Department of Animal Pathology, University of Zaragoza, 50013 Zaragoza, Spain;
| | - Lucas Gago
- Department of Mathematics and Computer Science, University of Barcelona, 08007 Barcelona, Spain;
| | - Telmo Fernandes
- Imaginologia Veterinaria do Porto, 4490-479 Porto, Portugal;
| | | | | | - Francesca Corda
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy;
| | - Pablo Gómez Ochoa
- VetCorner Unavets, 50012 Zaragoza, Spain; (M.D.A.); (P.G.O.)
- Department of Animal Pathology, University of Zaragoza, 50013 Zaragoza, Spain;
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Guerrero-Pérez F, Vilarrasa N, Huánuco LV, Busquets J, Secanella L, Vercher-Conejero JL, Vidal N, Näf Cortés S, Villabona C. Ectopic insulinoma: a systematic review. Rev Endocr Metab Disord 2023; 24:1135-1146. [PMID: 37434098 DOI: 10.1007/s11154-023-09824-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/07/2023] [Indexed: 07/13/2023]
Abstract
Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [68Ga]Ga-DOTA-exedin-4 PET/CT (100%), 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [68Ga]Ga-DOTA-exedin-4 PET/CT and 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.
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Affiliation(s)
- Fernando Guerrero-Pérez
- Department of Endocrinology, Bellvitge University Hospital, Barcelona, Spain.
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
| | - Nuria Vilarrasa
- Department of Endocrinology, Bellvitge University Hospital, Barcelona, Spain
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Lidia V Huánuco
- Department of Endocrinology, Bellvitge University Hospital, Barcelona, Spain
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Juli Busquets
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Hepatobiliary and Pancreatic Surgery, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Lluis Secanella
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Hepatobiliary and Pancreatic Surgery, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - José L Vercher-Conejero
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Nuclear Medicine-PET Unit, University Hospital Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Noemi Vidal
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Pathology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Silvia Näf Cortés
- Department of Endocrinology, Joan XXIII University Hospital, Tarragona, Spain
| | - Carles Villabona
- Department of Endocrinology, Bellvitge University Hospital, Barcelona, Spain
- Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
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Cui Y, Kozarek RA. Evolution of Pancreatic Endotherapy. Gastrointest Endosc Clin N Am 2023; 33:679-700. [PMID: 37709404 DOI: 10.1016/j.giec.2023.03.012] [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: 09/16/2023]
Abstract
In the last half century, endotherapy for pancreatic diseases has changed considerably. Although endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) were introduced initially as diagnostic tools, they quickly evolved into therapeutic tools for preventing and managing complications of pancreatitis. More recently, therapeutic endoscopy has shown potential in palliation and cure of pancreatic neoplasms. This article discusses the changing landscape of pancreatic endotherapy as therapeutic ERCP and EUS were introduced and because they have evolved to treat different diseases.
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Affiliation(s)
- YongYan Cui
- Department of Gastroenterology, Virginia Mason Medical Center
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Choi JH, Paik WH, Lee SH, Lee MW, Cho IR, Ryu JK, Kim YT. Efficacy and predictive factors of endoscopic ultrasound-guided ethanol ablation in benign solid pancreatic tumors. Surg Endosc 2023:10.1007/s00464-022-09833-3. [PMID: 37079095 PMCID: PMC10338579 DOI: 10.1007/s00464-022-09833-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 12/16/2022] [Indexed: 04/21/2023]
Abstract
BACKGROUNDS AND OBJECTIVES Endoscopic ultrasound-guided ethanol ablation (EUS-EA) has recently been introduced for the management of solid pancreatic tumors, including pancreatic neuroendocrine tumors (PNETs) and solid pseudopapillary tumors (SPTs). The study aims to evaluate the efficacy and predictive factors for response of EUS-EA in solid pancreatic tumors. METHODS Between October 2015 and July 2021, 72 patients who underwent EUS-EA for solid pancreatic tumors were included. The study outcomes were to evaluate the efficacy of EUS-EA with complete remission (CR) and objective response, and their predictive factors. RESULTS During follow-up, 47 patients were diagnosed with PNETs and 25 with SPTs. Eight cases reached CR and 48 reached objective response. When compared with SPTs, PNETs showed similar duration to reach CR (median not reached; p = 0.319), but shorter duration to reach objective response (PNETs: median 20.6 months, 95%CI 10.26-30.88; SPTs: median 47.7 months, 95%CI 18.14-77.20; p = 0.018). Ethanol dosage > 0.35 ml/cm3 shortened the duration to reach CR (median not reached; p = 0.026) and objective response (median 42.5 months, 95%CI 25.34-59.66 vs. 19.6 months, 95%CI 10.17-29.09; p = 0.006). CR had no significant predictive factors, but PNETs showed significant predictive factors for objective response (HR 3.34, 95%CI 1.07-10.43; p = 0.038). Twenty-seven patients experienced adverse events, and there were two severe cases. CONCLUSION EUS-EA for pancreatic solid lesions seems feasible as a local treatment for patients who refuse or are unfit for surgery. Additionally, PNETs seem to be the better candidate for EUS-EA.
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Affiliation(s)
- Jin Ho Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Woo Hyun Paik
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Min Woo Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - In Rae Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ji Kon Ryu
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong-Tae Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
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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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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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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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Zhang Y, Zheng DW, Li CX, Pan P, Zeng SM, Pan T, Zhang XZ. Temulence Therapy to Orthotopic Colorectal Tumor via Oral Administration of Fungi-Based Acetaldehyde Generator. SMALL METHODS 2022; 6:e2100951. [PMID: 35041291 DOI: 10.1002/smtd.202100951] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 11/05/2021] [Indexed: 06/14/2023]
Abstract
Taking inspiration from percutaneous ethanol injection (PEI) for tumor ablation, an acetaldehyde generator (SC@ZIF@ADH) is constructed for tumor treatment by modifying a metal-organic framework nanocarrier (ZIF), which is loaded with alcohol dehydrogenase (ADH), onto the surface of Saccharomyces cerevisiae (SC). Oral administration of SC@ZIF@ADH can target tumor via mannose-mediated targeting to tumor associated macrophages (TAMs) and generate ethanol at the hypoxic tumor areas. Ethanol is subsequently catalyzed to toxic acetaldehyde by ADH, inducing tumor cells apoptosis and polarizing TAMs toward the anti-tumor phenotype. In vivo animal results show that this acetaldehyde generator can cause a temulence-like reaction in the tumor, significantly inhibiting tumor progression, and might provide an intelligent and nonsurgical substitute for PEI therapy.
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Affiliation(s)
- Yu Zhang
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
| | - Di-Wei Zheng
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
| | - Chu-Xin Li
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
| | - Pei Pan
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
| | - Si-Min Zeng
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
| | - Ting Pan
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
| | - Xian-Zheng Zhang
- Key Laboratory of Biomedical Polymers of Ministry of Education, & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China
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10
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Altonbary A, Hakim H, Elkashef W. EUS-guided ethanol ablation of metastatic functional insulinoma. VideoGIE 2021; 6:443-445. [PMID: 34660943 PMCID: PMC8503933 DOI: 10.1016/j.vgie.2021.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Ahmed Altonbary
- Department of Gastroenterology and Hepatology, Mansoura Specialized Medical Hospital, Mansoura University, Mansoura, Egypt
| | - Hazem Hakim
- Department of Gastroenterology and Hepatology, Mansoura Specialized Medical Hospital, Mansoura University, Mansoura, Egypt
| | - Wagdi Elkashef
- Department of Pathology, Mansoura University, Mansoura, Egypt
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11
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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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12
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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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13
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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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14
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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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15
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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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16
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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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17
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Abstract
Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a “smart” multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: “Theranostic gastrointestinal endoscopy.” Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.
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18
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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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19
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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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20
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Hernández-Ludeña L, Consiglieri CF, Gornals JB. EUS-guided ethanol ablation therapy for gastric stromal tumors. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 110:69-70. [PMID: 29271220 DOI: 10.17235/reed.2017.5361/2017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
EUS-guided fine-needle ethanol injection (FNI) therapy of some types of cystic and solid tumors has been documented. However, reported cases to date of gastrointestinal-stromal tumors (GIST) treated with this technique are scarce. Ethanol ablation is an alternative treatment with a low rate of adverse events in selected cases.
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Affiliation(s)
- Lucía Hernández-Ludeña
- Endoscopy Unit, Instituto Oncológico Nacional "Dr. Juan Tanca Marengo", SOLCA, Guayaquil, Ecuador, Ecuador
| | - Claudia F Consiglieri
- Endoscopy Unit, Department of Digestive Disease, Hospital Universitari de Bellvitge-IDIBELL
| | - Joan B Gornals
- Endoscopia/Aparato Digestivo, Hospital Universitario de Bellvitge, España
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21
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Escartín R, Brun N, García Monforte MN, Ferreres JC, Corripio R. Insulinoma: A Rare Cause of Hypoglycemia in Childhood. AMERICAN JOURNAL OF CASE REPORTS 2018; 19:1121-1125. [PMID: 30237390 PMCID: PMC6161565 DOI: 10.12659/ajcr.910426] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patient: Male, 11 Final Diagnosis: Insulinoma Symptoms: Dizziness • psychological issues Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic
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Affiliation(s)
- Rocío Escartín
- Department of Pediatric Endocrinology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Nuria Brun
- Department of Surgery, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - M Nieves García Monforte
- Department of Surgery, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Joan Carles Ferreres
- Department of Pathology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Raquel Corripio
- Department of Pediatric Endocrinology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
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22
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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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23
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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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24
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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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25
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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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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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Recurrence of Metastatic Pro-insulinoma Nearly 50 Years After Subtotal Pancreatectomy. J Gastrointest Cancer 2017; 50:345-348. [DOI: 10.1007/s12029-017-0023-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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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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de Sousa Lages A, Paiva I, Oliveira P, Portela F, Carrilho F. Endoscopic ultrasound-guided ethanol ablation therapy for pancreatic insulinoma: an unusual strategy. Endocrinol Diabetes Metab Case Rep 2017; 2017:EDM160145. [PMID: 28458908 PMCID: PMC5404710 DOI: 10.1530/edm-16-0145] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 02/24/2017] [Indexed: 12/13/2022] Open
Abstract
Summary Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia. Although surgical enucleation is the standard treatment, a few other options are available to high-risk patients who are elderly or present with co-morbidities. We present a case report of an 89-year-old female patient who was admitted to the emergency department due to recurrent hypoglycaemia, especially during fasting. Laboratory work-up raised the suspicion of hyperinsulinaemic hypoglycaemia, and abdominal CT scan revealed a 12 mm nodular hypervascular lesion of the pancreatic body suggestive of neuroendocrine tumour. The patient was not considered a suitable candidate for surgery, and medical therapy with diazoxide was poorly tolerated. Endoscopic ultrasound-guided ethanol ablation therapy was performed and a total of 0.6 mL of 95% ethanol was injected into the lesion by a transgastric approach; no complications were reported after the procedure. At 5 months of follow-up, no episodes of hypoglycaemia were reported, no diazoxide therapy was necessary, and revaluation abdominal CT scan revealed a pancreatic nodular lesion with a size involution of about half of its original volume. The patient is regularly followed-up at the endocrinology clinic and shows a significant improvement in her wellbeing and quality of life. Learning points:
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Affiliation(s)
| | - Isabel Paiva
- Departments of Endocrinology, Diabetes and Metabolism
| | | | - Francisco Portela
- Departments of Gastroenterology, Coimbra Hospital and University Center, Coimbra, Portugal
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Han J, Chang KJ. Endoscopic Ultrasound-Guided Direct Intervention for Solid Pancreatic Tumors. Clin Endosc 2017; 50:126-137. [PMID: 28391669 PMCID: PMC5398363 DOI: 10.5946/ce.2017.034] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 03/23/2017] [Accepted: 03/23/2017] [Indexed: 12/13/2022] Open
Abstract
Development and use of linear-array echoendoscope and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) have made endoscopic ultrasound (EUS) more of an interventional procedure than a purely diagnostic procedure. This is a literature review of previously published clinical studies on EUS-guided direct intervention for solid pancreatic tumors, including EUS-guided fine needle injection (EUS-FNI) of antitumor agents, EUS-guided fiducial marker placement, EUS-guided brachytherapy and EUS-guided tumor ablation.
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Affiliation(s)
- Jimin Han
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Kenneth J. Chang
- Division of Gastroenterology and Hepatology, H.H. Chao Comprehensive Digestive Disease Center, University of California, Irvine, Orange, CA, USA
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Abstract
Initially, endoscopic ultrasound (EUS) was developed to inspect the pancreas and other organs adjacent to the gastrointestinal tract. After introduction of curvilinear-array echoendoscopes, EUS has been used for a variety of interventions in gastroenterology, including fine needle aspiration, pancreatobiliary drainage and tumor ablation. EUS-guided ablation of pancreatic cystic tumors with ethanol and with or without cytotoxic agents has been studied, showing its potential to become an alternative to surgery. However, only few attempts at using ethanol ablation to treat solid pancreatic tumors have been reported. Recently, EUS-guided radiofrequency ablation was introduced and has been cautiously applied for pancreatic cancer. This article focuses on the clinical application of EUS for the ablation of solid pancreatic tumors.
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Affiliation(s)
- Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Wan Seo
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Burghardt K, Kaemmerer D, Michael A, Aschenbach R, Müller UA, Kloos C, Wolf G. Successful endoscopic ultrasound-guided ethanol ablation of a symptomatic sporadic insulinoma in a patient with severe comorbidities not suitable for pancreatic surgery. DIABETES & METABOLISM 2017; 44:84-86. [PMID: 28161372 DOI: 10.1016/j.diabet.2016.12.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 12/15/2016] [Accepted: 12/26/2016] [Indexed: 11/24/2022]
Affiliation(s)
- K Burghardt
- Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine III, Jena University Hospital, Jena, Germany.
| | - D Kaemmerer
- Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany
| | - A Michael
- Gastroenterology, Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - R Aschenbach
- Institute of Diagnostical and Interventional Radiology, Jena University Hospital, Jena, Germany
| | - U A Müller
- Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine III, Jena University Hospital, Jena, Germany
| | - C Kloos
- Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine III, Jena University Hospital, Jena, Germany
| | - G Wolf
- Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine III, Jena University Hospital, Jena, Germany
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Abstract
Insulinomas are rare neuroendocrine tumors which occur predominantly in the pancreas. Although majority of the insulinomas are benign, over-secretion of insulin by the tumor leads to debilitating hypoglycemic symptoms. The diagnosis is based on clinical and biochemical findings. After the diagnosis is made, the principal challenge lies in locating the tumor because most tumors are solitary and small in size. Locating the tumor is of paramount importance as complete surgical excision is the only curative treatment, and incomplete resection leads to persistence of symptoms. Different preoperative and intraoperative imaging techniques have been used with varying success rates for the insulinoma imaging. Besides localizing the tumor, imaging also helps to guide biopsy, detect metastatic lesions, and perform image-guided therapeutic procedures. This review will discuss the role of different Cross sectional and nuclear medicine imaging modalities in insulinomas.
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35
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Braden B, Jenssen C, D'Onofrio M, Hocke M, Will U, Möller K, Ignee A, Dong Y, Cui XW, Sãftoiu A, Dietrich CF. B-mode and contrast-enhancement characteristics of small nonincidental neuroendocrine pancreatic tumors. Endosc Ultrasound 2017; 6:49-54. [PMID: 28218201 PMCID: PMC5331844 DOI: 10.4103/2303-9027.200213] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Imaging of the pancreas for detection of neuroendocrine tumors is indicated as surveillance in multiple endocrine neoplasia type 1 (MEN1) or if typical clinical symptoms combined with hormone production raise the suspicion of a neuroendocrine tumor. Endoscopic ultrasound (EUS) is considered the best imaging modality to detect small pancreatic tumors. However, little is known about how small pancreatic neuroendocrine tumors (pNETs) present on EUS. PATIENTS AND METHODS In this multicenter study, we retrospectively analyzed the endosonographic characteristics of small pNETs which had been detected due to typical biochemistry and clinical symptoms or during surveillance of MEN 1. Only small pancreatic tumors ≤15 mm with histological confirmation as pNET were included. B-mode and contrast-enhanced ultrasound- and EUS patterns were analyzed. RESULTS Among 32 patients with histologically proven small pNETs, 7 patients had known MEN1. Among the pNETs, 20 were insulinoma, 2 gastrinoma, 3 glucagonoma, 6 nonfunctional in MEN1, and one PPoma. 94% of the pNET appeared hypoechogenic, only 1 isoechogenic and 1 hyperechogenic. After contrast injection, 90% of the pNETS showed hyperenhancement compared to the surrounding pancreatic parenchyma. CONCLUSION The high spatial resolution of EUS allows detection and even cytological confirmation of pNET <7 mm diameter. Hypoechogenicity in B-mode and hyperenhancement after injection of contrast agents are endosonographic characteristics of small pNET and present in >90% of pNETs.
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Affiliation(s)
- Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | - Christian Jenssen
- Medical Department, Krankenhaus Maerkisch-Oderland, Strausberg, Germany
| | - Mirko D'Onofrio
- Department of Radiology, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - Michael Hocke
- Medical Department, Helios Klinikum Meiningen, Meiningen, Germany
| | - Uwe Will
- SRH Wald-Klinikum Gera, Gera, Germany
| | - Kathleen Möller
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Andre Ignee
- Medical Department, Caritas-Krankenhaus, Uhlandstr. 7 D-97980 Bad Mergentheim, Germany
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Adrian Sãftoiu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Christoph F Dietrich
- Medical Department, Caritas-Krankenhaus, Uhlandstr. 7 D-97980 Bad Mergentheim, Germany; Sino-German Research Center of Ultrasound in Medicine, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Ito T, Lee L, Jensen RT. Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies. Expert Opin Pharmacother 2016; 17:2191-2205. [PMID: 27635672 DOI: 10.1080/14656566.2016.1236916] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is aggressive and a proportion has a functional, hormone-excess-state(F-NET), each of which must be treated. Recently, there have been many advances, well-covered in reviews/consensus papers on imaging-NETs; new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state. These advances are usually reported in case-series, and case-reports with few large studies. In this paper these advances are reviewed. Areas covered: Advances in the last 5-years are concentrated on, but a review of literature from the last 10-years was performed. PubMed and other databases (Cochrane, etc.) were searched for F-NET-syndromes including carcinoid-syndrome, as well as meeting-abstracts on NETs. All advances that controlled hormone-excess-states or facilitated-control were covered. These include new medical-therapies [serotonin-synthesis inhibitors(telotristat), Pasireotide, new agents for treating ACTHomas], increased dosing with conventional therapies (octreotide-LAR, Lanreotide-Autogel), mTor inhibitors(everolimus), Tyrosine-kinase inhibitors(sunitinib),cytoreductive surgery, liver-directed therapies (embolization, chemoembolization, radioembolization, RFA), peptide radio-receptor-therapy(PRRT) and 131I-MIBG, ablation of primary F-NETs. Expert opinion: Although many of the newer therapies controlling the hormone-excess-states in F-NETs are reported in relatively few patients, all the approaches show promise. Their description also generates some controversies/unresolved areas,such as the order of these new treatments, their longterm-efficacy, and effectiveness of combinations which may require large,controlled studies.
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Affiliation(s)
- Tetsuhide Ito
- a Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences , Kyushu University , Fukuoka , Japan
| | - Lingaku Lee
- a Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences , Kyushu University , Fukuoka , Japan
| | - Robert T Jensen
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
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Trikudanathan G, Mallery SJ, Amateau SK. Successful Endoscopic Ultrasound-Guided Alcohol Ablation of Sporadic Insulinoma Using Three-Dimensional Targeting (with Video). Clin Endosc 2016; 49:399-401. [PMID: 27000426 PMCID: PMC4977744 DOI: 10.5946/ce.2015.144] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 01/27/2016] [Indexed: 12/15/2022] Open
Abstract
Surgical resection is considered the standard of care in the management of symptomatic insulinoma. In this video, we describe the successful management of a symptomatic insulinoma by using linear array endoscopic ultrasound (EUS)-guided ethanol ablation in a poor surgical candidate. EUS-guided ethanol ablation of insulinoma offers a safer, effective, and less invasive alternative to surgery.
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Affiliation(s)
- Guru Trikudanathan
- Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Shawn J Mallery
- Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Stuart K Amateau
- Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
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Shen YH, Liu AQ. Endoscopic ultrasonography in interventional diagnosis and treatment of digestive diseases. Shijie Huaren Xiaohua Zazhi 2016; 24:833-841. [DOI: 10.11569/wcjd.v24.i6.833] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Since 1980, when endoscopic ultrasonography (EUS) was invented, great progress has been made in the development of EUS devices and technology, and EUS-guided diagnosis and treatment of digestive diseases have been widely adopted. Because of its safety, effectiveness and minimal invasion, EUS-guided interventional diagnosis and treatment of digestive diseases have been widely applied in the clinical work, and more and more new technologies are being developed. In this paper, we review the recent progress of EUS for the interventional diagnosis and treatment of digestive diseases.
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Armellini E, Crinò SF, Ballarè M, Pallio S, Occhipinti P. Endoscopic ultrasound-guided ethanol ablation of pancreatic neuroendocrine tumours: A case study and literature review. World J Gastrointest Endosc 2016; 8:192-197. [PMID: 26862370 PMCID: PMC4734979 DOI: 10.4253/wjge.v8.i3.192] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 08/20/2015] [Accepted: 10/13/2015] [Indexed: 02/05/2023] Open
Abstract
Here we offer a review of the literature regarding endoscopic ultrasound-guided ethanol ablation for pancreatic neuroendocrine tumours and describe the case of a cystic tumour completely ablated after a multisession procedure. A total of 35 PubMed indexed cases of treated functioning and non-functioning pancreatic neuroendocrine tumours resulted from our search, 29 of which are well-documented and summarised. Endoscopic ultrasound-guided ethanol ablation appears as a local, minimally invasive treatment of pancreatic neuroendocrine tumours, suitable for selected patients. This technique appears feasible, relatively safe and efficient, especially when applied to symptom relief in functioning tumours, aiming at loss of endocrine secretion. For non-functioning tumours, where the goal is complete tissue ablation, eus guided ethanol ablation can provide good results for patients who are unfit for surgery or for those who refuse surgical resection. Its role in “fit for surgery” patients requires assessment through further studies.
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Holstein A, Morgenstern T, Dienst H, Hiller W. Insulinoma as rare cause of severe post-partum hypoglycemia. J Obstet Gynaecol Res 2015; 41:1848-50. [PMID: 26399682 DOI: 10.1111/jog.12785] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Revised: 05/11/2015] [Accepted: 05/18/2015] [Indexed: 12/27/2022]
Abstract
Post-partum hypoglycemia in non-diabetic women is a rare condition. We report the exceptional case of a 38-year-old obese woman who experienced recurrent neuroglycopenia 3 weeks after delivery. Corresponding to severe hypoglycemia with blood glucose levels of <30 mg/dL, there was no suppression of insulin or C-peptide. Through endoscopic ultrasound we detected a hypoechoic lesion of 8 × 9 mm localized in the head of the pancreas. Thus, the diagnosis of insulinoma was most probable. Complete surgical enucleation of the insulinoma resulted in immediate and permanent resolution of hypoglycemia. The postoperative course was complicated by recurrent episodes of pancreatitis requiring endoscopic ultrasound-guided punctures of pseudocysts and temporary stenting of the pancreatic duct. In conclusion, insulinoma is a very rare, nonetheless important, differential diagnosis of post-partum hypoglycemia.
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Affiliation(s)
| | | | - Henry Dienst
- Department of Surgery, Lippe-Detmold Hospital, Detmold, Germany
| | - Wolfgang Hiller
- Department of Surgery, Lippe-Detmold Hospital, Detmold, Germany
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