• Users Online:96
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2019  |  Volume : 8  |  Issue : 4  |  Page : 220-226

EUS-guided radiofrequency ablation as an alternative to surgery for pancreatic neuroendocrine neoplasms: Who should we treat?

1 Digestive Endoscopy Unit, Foundation University Policlinico Hospital A. Gemelli, IRCCS, Catholic University, Rome, Italy
2 Digestive Endoscopy Unit; Division of Gastroenterology, Foundation University Policlinico Hospital A. Gemelli, IRCCS, Catholic University, Rome, Italy
3 Digestive Endoscopy Unit, Foundation University Policlinico Hospital A. Gemelli, IRCCS, Catholic University, Rome, Italy; Department of Gastroenterology, Colentina Clinical Hospital, Carol Davila University of Medicine, Bucharest, Romania
4 Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University Hospital of Verona, Verona, Italy
5 Division of Gastroenterology, Foundation University Policlinico Hospital A. Gemelli, IRCCS, Catholic University, Rome, Italy
6 Digestive Endoscopy Unit, Foundation University Policlinico Hospital A. Gemelli, IRCCS, Catholic University, Rome, Italy; IHU-USIAS, University of Strasbourg, Strasbourg, France

Date of Submission25-Oct-2018
Date of Acceptance10-Apr-2019
Date of Web Publication20-Jun-2019

Correspondence Address:
Dr. Alberto Larghi
Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo A. Gemelli 8, 00168, Rome
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/eus.eus_28_19

Rights and Permissions

Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors, but their incidental diagnosis has significantly increased due to the widespread use of imaging studies. Therefore, most PanNENs are now diagnosed when completely asymptomatic and in early stages. PanNENs are classified according to their grade (Ki-67 index) and can be functional (F-) or nonfunctional (NF-) depending on the presence or absence of a clinical, hormonal hypersecretion syndrome. The mainstay treatment of PanNENs is a surgery that is mostly curative but also associated with significant short- and long-term adverse events. Therefore, less invasive alternative locoregional treatment modalities are warranted. Recently, few case reports and two case series have described EUS-guided radiofrequency ablation (EUS-RFA) for the treatment of patients with both F-PanNENs and NF-PanNENs. If for F-PanNENs EUS-RFA can very easily become the standard of care, for NF-PanNENEs it is still controversial how to select patients for EUS-RFA. A balance between overtreatment (i.e., RFA/surgery in patients who will not progress) and undertreatment (locoregional treatments in patients with undetected metastases) needs to be found based on solid data. The decision should also take into account patients' comorbidity and risk of postoperative death, life expectancy, tumor location, risk of postoperative fistula and postoperative morbidity, and risk of long-term exocrine and/or endocrine insufficiency. To answer the important question on which a patient should be treated with EUS-RFA, properly designed studies to evaluate the efficacy of this treatment in large cohorts of patients with NF-PanNENs and to establish prognostic factors associated with treatment response are urgently needed.

Keywords: EUS, individualized therapy, pancreatic neuroendocrine neoplasms, radiofrequency ablation

How to cite this article:
Larghi A, Rizzatti G, Rimbaş M, Crino SF, Gasbarrini A, Costamagna G. EUS-guided radiofrequency ablation as an alternative to surgery for pancreatic neuroendocrine neoplasms: Who should we treat?. Endosc Ultrasound 2019;8:220-6

How to cite this URL:
Larghi A, Rizzatti G, Rimbaş M, Crino SF, Gasbarrini A, Costamagna G. EUS-guided radiofrequency ablation as an alternative to surgery for pancreatic neuroendocrine neoplasms: Who should we treat?. Endosc Ultrasound [serial online] 2019 [cited 2020 Jul 6];8:220-6. Available from: http://www.eusjournal.com/text.asp?2019/8/4/220/260855

  Introduction Top

Pancreatic neuroendocrine neoplasms (PanNENs) are rare, but their incidence has significantly increased in the last decades due to the widespread use of imaging studies.[1],[2],[3] This has led to the incidental diagnosis of a higher number of PanNENs completely asymptomatic and in early stages.[4],[5] Although they represent ~1% of all pancreatic neoplasms, their prevalence is about 10%, mostly accounting for low-to-intermediate grade neuroendocrine tumors with a relatively “indolent” clinical course.[1],[6] The WHO 2017 classification of PanNENs distinguishes between well-differentiated neuroendocrine tumors (PanNETs) and poorly differentiated neuroendocrine carcinomas (PanNECs). PanNETs are then divided according to a grading scheme based on Ki-67 index in PanNETs-G1 (Ki-67 index ≤3%) and PanNETs-G2 (Ki-67 index between 4% and 20%). PanNECs are all G3, with a Ki-67 index >20%.[7] PanNENs are classified as functional (F-) or nonfunctional (NF-) depending on the presence or absence of a clinical, hormonal hypersecretion syndrome, and the clinical management of these lesions is challenging. The mainstay treatment of PanNENs is surgery, which is associated with a significant benefit in terms of survival.[8] The surgical treatment of localized PanNENs includes both typical and atypical resections. Atypical surgeries, mostly used for well-demarcated and small-sized PanNENs, have been developed to decrease rates of long-term endocrine and/or exocrine impairment observed after typical resection.[9],[10],[11] Despite curative, pancreatic surgery is associated with significant short- and long-term adverse events (AEs). A recent systematic review of the literature, including 62 studies, evaluating the most common postoperative complications in PanNENs, has reported that pancreatic fistula occurred in 45% of the cases after tumor enucleation, in 14% after both distal pancreatectomy and pancreatoduodenectomy, and in 58% after central pancreatectomy.[12] Delayed gastric emptying was observed in 5% of the patients after both enucleation and distal pancreatectomy, in 18% after pancreatoduodenectomy, and in 15% after central pancreatectomy.[12] Overall, postoperative hemorrhage occurred in 6% of the cases, in particular in 1% after distal pancreatectomy, in 7% after pancreatoduodenectomy, and in 4% after central pancreatectomy. The overall pooled in-hospital mortality was 4% in distal pancreatectomy, 6% in pancreatoduodenectomy, and 4% in central pancreatectomy.[12] Based on the above data, less invasive alternative therapeutic interventions to avoid short- and long-term AEs of surgery are warranted.

  Radiofrequency Ablation for Pannens and Conclusions Top

Recently, few case reports and two case series have described radiofrequency ablation under EUS guidance (EUS-RFA) for the treatment of patients with both F-PanNENs and NF-PanNENs.[13],[14],[15],[16],[17],[18],[19],[20]

Despite the limited number of published studies, interpretation of results is difficult due to the heterogeneity of these studies in terms of patients and outcome selection. Important variables to consider when evaluating patients for EUS-RFA are the type of PanNENs (functional or nonfunctional), number and dimension of the lesions, and grading and staging of the disease. [Table 1] reports the main characteristics of available studies on EUS-RFA for PanNENs.
Table 1: Characteristics of patients with nonfunctional pancreatic neuroendocrine neoplasms and outcome of their surveillance strategy

Click here to view

For F-PanNENs, the goal of treatment is to induce necrosis and death of the large majority of the neuroendocrine tumor cells to abate the hormonal hypersecretion with cessation of symptoms, without the need to obtain complete ablation of the tumor because of its very low malignant potential. Available studies, mostly case report and case series, report that all F-PanNENs were treated without any AEs and showed complete regression of the clinical syndrome.[17],[18],[19],[20] In these studies, F-PanNENs were all single insulinomas with a diameter inferior to 20 mm. If the data on F-PanNENs will be replicated on a large cohort prospectively enrolled, EUS-RFA can become the standard of care for these patients, independently on patients and tumor's variables.

For NF-PanNENs, the decision-making process to determine which patients can benefit the most from RFA treatment is more complex than for F-PanNENs. A balance between overtreatment (i.e., RFA/surgery in patients who will not progress) and undertreatment (locoregional treatment in patients with undetected metastases) needs to be found based on the available data. Some investigators, despite all the possible AEs of surgery, redundantly favor resecting all NF-PanNENs to avoid growth and progression.[28],[29],[30],[31],[32] On the other hand, several studies explored the safety and feasibility of a nonoperative management approach (“wait-and-see” strategy) for asymptomatic, incidentally discovered NF-PanNENs ≤2 cm[21],[22],[23],[24],[25],[26],[27] [Table 2].
Table 2: Characteristics of available studies on EUS-radiofrequency ablation for pancreatic neuroendocrine neoplasms

Click here to view

A conservative approach seemed to be safe as the majority of the observed tumors did not show any significant changes during the follow-up.[21],[22],[23],[24],[25],[26],[27] Tumor growth occurred in about one-fourth of the patients (84/358; 23.5%), while surgery was performed in only 49/358 (14.1%). Lymph node metastases were not detected in any patients, while distant liver metastases were detected in the study by Rosenberg et al.[25] in three of the 15 patients under surveillance. Based on all these data, the European Neuroendocrine Tumor Society (ENETS) developed guidelines recommending surveillance for the management of patients with lesions ≤2 cm.[34] However, with the exception of the study by Sadot et al.,[27] which is a well-designed matched case–control study, all the other studies are retrospective with a low level of evidence and with a short follow-up, which preclude drawing any definitive conclusions about tumor diameter cutoff to identify patients who could benefit from the “wait-and-see” approach versus upfront surgery.[35] Moreover, although the cutoff level of ≤2 cm has been widely adopted, other studies have found that larger NF-PanNENs size up to 3 cm did not correlate with behavior, and factors other than size are important.[36] Jiang et al.[37] found a correlation between radiologic diameter of 2.5 cm, high tumor grade, symptoms, and lymph nodes metastases. Salinen et al.[34] stratified NF-PanNENs into three groups: <2 cm, between 2 and 4 cm, and >4 cm and noted that size alone did not predict behavior. Finally, a study by Ricci et al.[38] retrospectively evaluating 102 surgically treated patients affected by NF-PanNENs found that some small tumors (≤2 cm) were T3–4 in 11% and G2–3 in 36.6% of cases. Moreover, lymph node and distant metastases were present in 31% and 8% of the cases, respectively.[38] Exclusion of lymph nodes, liver, and other distant metastases is of paramount importance to enroll a patient for RFA treatment. Regarding lymph nodes metastases, in a study on 181 patients who underwent surgical resection, 55 (30%) of them were found to have lymph nodes metastases.[39] At multivariate analysis, radiologically detected lymph nodes metastases and tumor grade (G2 vs. G1) were the independent risk factors associated with lymph nodes metastases. When tumor grade was excluded, radiologically detected lymph nodes metastases and tumor size larger than 4 cm were the independent risk factors associated with lymph nodes metastases.[39] Based on the ENETS guidelines, staging of patients with NF-PanNENs should be performed using a combination of multidetector computed tomography (CT), magnetic resonance imaging (MRI), and 68Ga-DOTATATE positron emission tomography (PET)-CT with overall good results.[40],[41],[42],[43] All these imaging modalities should also be used during follow-up to monitor for disease recurrence at distant sites. Finally, risk stratification also involves the determination of tumor grade. Data on tumor grading in patients who underwent surveillance are limited and reflect the low reliability of cytological determination of Ki-67 on samples acquired under EUS examination. This is due to the heterogeneity of the distribution of Ki-67 within the tumor, making possible a underestimation of the grading of pancreatic sampling.[44],[45] In the study by Jung et al.,[26] only four out of 77 patients (5.2%) had Ki-67 detection available, which was G1 in three patients and G3 in one patient. In another study by Rosenberg et al.,[25] four out of 15 patients (26.7%) had available Ki-67 determination that showed G2 tumors in all of them. Finally, in the study by Lee et al.,[21] 14 of the 77 patients under surveillance had biopsy done that showed a Ki-67 <5% in all cases. At present, very scanty data are available comparing the reproducibility of the grading on biopsy samples acquired with EUS-guided tissue acquisition as compared with that of surgical specimens. One study by Larghi et al.[46] using a 19G fine-needle aspiration needle has reported a diagnostic accuracy of 93.3% and a capability of measuring Ki-67 expression in 86.6% and 92.9% of cases. Preoperative and postoperative Ki-67 proliferation indexes were concordant in 83.3% of the patients, whereas two patients were upstaged from G1 to G2 or downstaged from G2 to G1, respectively. Interestingly, when a cutoff of >5% to define G2 tumors, which seems to be more useful than the 3% value to stratify prognosis of patients with NF-PanNENs within the same disease stage,[47],[48],[49] was applied, a concordance was found in all cases. Newly developed needles, specifically designed to acquire tissue core biopsy, have been recently become available, which may result in a better performance.[50] Although Ki-67 determination cannot be completely reliable, it can be used together with all the other collected information to reach the final decision on which patients to set for RFA. Among other prognostic factors, incidentally discovered asymptomatic tumors have a greater 5-year progression-free survival than symptomatic tumors.[23],[51] Moreover, the presence of calcifications and hypoenhancing tumors is both associated with a higher probability of lymph node and liver metastasis.[52],[53],[54]

Regarding EUS-RFA for NF-PanNENs, in a case series by Choi et al.,[20] seven patients with a median tumor diameter of 20 mm (range 8–28) were treated with 13 sessions of EUS-RFA. Complete response was achieved in five patients, while two had persistent PanNENs. Regarding AEs, one patient developed abdominal pain and one developed mild pancreatitis that resolved with conventional therapy. In a second series by Barthet et al.,[33] 12 patients with 13 NF-PanNEN lesions <2 cm (mean 13.1 mm, range 10–20) were treated with EUS-RFA. At 6 months, complete response was achieved in nine lesions (71%), a volume reduction of >50% diameter was observed in one case, while a decrease in diameter <50% in three and no changes in another one were noticed. At 1-year follow-up evaluation, 12 out of the 13 NF-PanNENs had complete disappearance or necrosis of the lesion (92.3%). AEs were observed in two patients, with one case of pancreatitis that was treated conservatively and one case of main pancreatic duct (MPD) stenosis 7 days after the procedure in a patient treated for a 12 mm NF-PNEN located in the pancreatic neck, 1 mm close to the MPD. Pancreatitis occurred at the first patient treated and made the authors to modify their protocol introducing prophylactic indomethacin 100 mg suppositories. No more cases of pancreatitis were observed thereafter.

Based on all the data presented above, it is still controversial how to select patients for EUS-RFA. This decision should also be balanced with patients comorbidity and risk of postoperative death, life expectancy, tumor location (pancreaticoduodenectomy carries a higher risk than distal resection), risk of postoperative fistula and postoperative morbidity, and risk of long-term exocrine and endocrine insufficiency. Moreover, it is important to remember that EUS-RFA treatment does not preclude subsequent surgery, which can be done in cases of failure. To answer the important question on which patient should be treated with EUS-RFA, properly designed studies to evaluate the efficacy of EUS-RFA treatment in large cohort of patients with NF-PanNENs and to establish prognostic factors associated with treatment response are urgently needed. These studies should be prospective, multicenter to reach a meaningful number of patients, with strict enrollment criteria decided upon a multidisciplinary discussion.

To fill in this gap, we have designed a large prospective study (registered at Clinical. Trials.gov NCT03834701) involving 11 centers (7 centers are ENETS Center of Excellence) with the following entry criteria:

  • Distance from the MPD <2 mm
  • Single lesion visualized at CT, and/or MRI, and/or EUS
  • EUS-FNB-proven NF-PanNENs
  • 68Ga-DOTATATE PET/CT positive for a pancreatic lesion and negative for lymph nodes, liver, and other distant metastases
  • Hyper- or iso-enhancing pattern at MRI and/or CT with negative lymph nodes, liver, and other distant metastases and absence of inner calcifications
  • G1 or G2 ≤5% on histological examination of EUS-guided biopsy samples utilizing FNB needles
  • Diameter between 15 and 25 mm
  • Absence of symptoms
  • For F-PanNENs, a definitive diagnosis of a clinical syndrome related to excessive insulin secretion fasting test, insulin blood levels, C-peptide blood levels and size <20 mm.

Each patient fulfilling the entry criteria will be further evaluated in a multidisciplinary meeting to establish the definitive enrollment into the study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063-72.  Back to cited text no. 1
Halfdanarson TR, Rubin J, Farnell MB, et al. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat Cancer 2008;15:409-27.  Back to cited text no. 2
Vagefi PA, Razo O, Deshpande V, et al. Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: The Massachusetts general hospital experience from 1977 to 2005. Arch Surg 2007;142:347-54.  Back to cited text no. 3
Yao JC, Eisner MP, Leary C, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol 2007;14:3492-500.  Back to cited text no. 4
Hallet J, Law CH, Cukier M, et al. Exploring the rising incidence of neuroendocrine tumors: A population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer 2015;121:589-97.  Back to cited text no. 5
Fitzgerald TL, Hickner ZJ, Schmitz M, et al. Changing incidence of pancreatic neoplasms: A 16-year review of statewide tumor registry. Pancreas 2008;37:134-8.  Back to cited text no. 6
Kloppel G, Couvelard A, Hruban RH, et al. Neoplasms of the neuroendocrine pancreas, Introduction. In: Lloyd RV, Osamura Y, Kloppel G, et al., editors. WHO Classification of Tumours of Endocrine Organs. Lyon: France: International Agency for Research on Cancer (IARC); 2017. p. 211-4.  Back to cited text no. 7
Hill JS, McPhee JT, McDade TP, et al. Pancreatic neuroendocrine tumors: The impact of surgical resection on survival. Cancer 2009;115:741-51.  Back to cited text no. 8
Falconi M, Zerbi A, Crippa S, et al. Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. Ann Surg Oncol 2010;17:1621-7.  Back to cited text no. 9
Falconi M, Mantovani W, Crippa S, et al. Pancreatic insufficiency after different resections for benign tumours. Br J Surg 2008;95:85-91.  Back to cited text no. 10
Aranha GV, Shoup M. Nonstandard pancreatic resections for unusual lesions. Am J Surg 2005;189:223-8.  Back to cited text no. 11
Jilesen AP, van Eijck CH, in't Hof KH, et al. Postoperative complications, in-hospital mortality and 5-year survival after surgical resection for patients with a pancreatic neuroendocrine tumor: A systematic review. World J Surg 2016;40:729-48.  Back to cited text no. 12
Limmer S, Huppert PE, Juette V, et al. Radiofrequency ablation of solitary pancreatic insulinoma in a patient with episodes of severe hypoglycemia. Eur J Gastroenterol Hepatol 2009;21:1097-101.  Back to cited text no. 13
Rossi S, Viera FT, Ghittoni G, et al. Radiofrequency ablation of pancreatic neuroendocrine tumors: A pilot study of feasibility, efficacy, and safety. Pancreas 2014;43:938-45.  Back to cited text no. 14
Pai M, Habib N, Senturk H, et al. Endoscopic ultrasound guided radiofrequency ablation, for pancreatic cystic neoplasms and neuroendocrine tumors. World J Gastrointest Surg 2015;7:52-9.  Back to cited text no. 15
Armellini E, Crinò SF, Ballarè M, et al. Endoscopic ultrasound-guided radiofrequency ablation of a pancreatic neuroendocrine tumor. Endoscopy 2015;47 Suppl 1:E600-1.  Back to cited text no. 16
Waung JA, Todd JF, Keane MG, et al. Successful management of a sporadic pancreatic insulinoma by endoscopic ultrasound-guided radiofrequency ablation. Endoscopy 2016;48 Suppl 1:E144-5.  Back to cited text no. 17
Lakhtakia S, Ramchandani M, Galasso D, et al. EUS-guided radiofrequency ablation for management of pancreatic insulinoma by using a novel needle electrode (with videos). Gastrointest Endosc 2016;83:234-9.  Back to cited text no. 18
Bas-Cutrina F, Bargalló D, Gornals JB. Small pancreatic insulinoma: Successful endoscopic ultrasound-guided radiofrequency ablation in a single session using a 22-G fine needle. Dig Endosc 2017;29:636-8.  Back to cited text no. 19
Choi JH, Seo DW, Song TJ, et al. Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors. Endoscopy 2018;50:1099-104.  Back to cited text no. 20
Lee LC, Grant CS, Salomao DR, et al. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): Role for nonoperative management. Surgery 2012;152:965-74.  Back to cited text no. 21
Gaujoux S, Partelli S, Maire F, et al. Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab 2013;98:4784-9.  Back to cited text no. 22
Crippa S, Partelli S, Zamboni G, et al. Incidental diagnosis as prognostic factor in different tumor stages of nonfunctioning pancreatic endocrine tumors. Surgery 2014;155:145-53.  Back to cited text no. 23
Kishi Y, Shimada K, Nara S, et al. Basing treatment strategy for non-functional pancreatic neuroendocrine tumors on tumor size. Ann Surg Oncol 2014;21:2882-8.  Back to cited text no. 24
Rosenberg AM, Friedmann P, Del Rivero J, et al. Resection versus expectant management of small incidentally discovered nonfunctional pancreatic neuroendocrine tumors. Surgery 2016;159:302-9.  Back to cited text no. 25
Jung JG, Lee KT, Woo YS, et al. Behavior of small, asymptomatic, nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Medicine (Baltimore) 2015;94:e983.  Back to cited text no. 26
Sadot E, Reidy-Lagunes DL, Tang LH, et al. Observation versus resection for small asymptomatic pancreatic neuroendocrine tumors: A matched case-control study. Ann Surg Oncol 2016;23:1361-70.  Back to cited text no. 27
Finkelstein P, Sharma R, Picado O, et al. Pancreatic neuroendocrine tumors (panNETs): Analysis of overall survival of nonsurgical management versus surgical resection. J Gastrointest Surg 2017;21:855-66.  Back to cited text no. 28
Haynes AB, Deshpande V, Ingkakul T, et al. Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: Short-term and long-term patient outcomes. Arch Surg 2011;146:534-8.  Back to cited text no. 29
Sharpe SM, In H, Winchester DJ, et al. Surgical resection provides an overall survival benefit for patients with small pancreatic neuroendocrine tumors. J Gastrointest Surg 2015;19:117-23.  Back to cited text no. 30
Öberg K, Knigge U, Kwekkeboom D, et al. Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23 Suppl 7:vii124-30.  Back to cited text no. 31
Gratian L, Pura J, Dinan M, et al. Impact of extent of surgery on survival in patients with small nonfunctional pancreatic neuroendocrine tumors in the United States. Ann Surg Oncol 2014;21:3515-21.  Back to cited text no. 32
Barthet M, Giovannini M, Lesavre N, et al. Endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors and pancreatic cystic neoplasms: A prospective multicenter study. Endoscopy 2019. [Epub ahead of print].  Back to cited text no. 33
Falconi M, Eriksson B, Kaltsas G, et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 2016;103:153-71.  Back to cited text no. 34
Sallinen V, Le Large TY, Galeev S, et al. Surveillance strategy for small asymptomatic non-functional pancreatic neuroendocrine tumors – A systematic review and meta-analysis. HPB (Oxford) 2017;19:310-20.  Back to cited text no. 35
Gorelik M, Ahmad M, Grossman D, et al. Nonfunctioning incidental pancreatic neuroendocrine tumors: Who, when, and how to treat? Surg Clin North Am 2018;98:157-67.  Back to cited text no. 36
Jiang Y, Jin JB, Zhan Q, et al. Impact and clinical predictors of lymph node metastases in nonfunctional pancreatic neuroendocrine tumors. Chin Med J (Engl) 2015;128:3335-44.  Back to cited text no. 37
Ricci C, Taffurelli G, Campana D, et al. Is surgery the best treatment for sporadic small (≤2 cm) non-functioning pancreatic neuroendocrine tumours? A single centre experience. Pancreatology 2017;17:471-7.  Back to cited text no. 38
Partelli S, Gaujoux S, Boninsegna L, et al. Pattern and clinical predictors of lymph node involvement in nonfunctioning pancreatic neuroendocrine tumors (NF-panNETs). JAMA Surg 2013;148:932-9.  Back to cited text no. 39
Schraml C, Schwenzer NF, Sperling O, et al. Staging of neuroendocrine tumours: Comparison of [68Ga] DOTATOC multiphase PET/CT and whole-body MRI. Cancer Imaging 2013;13:63-72.  Back to cited text no. 40
Albanus DR, Apitzsch J, Erdem Z, et al. Clinical value of 68Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). Eur J Radiol 2015;84:1866-72.  Back to cited text no. 41
Basu S, Ranade R, Ostwal V, et al. PET-based molecular imaging in designing personalized management strategy in gastroenteropancreatic neuroendocrine tumors. PET Clin 2016;11:233-41.  Back to cited text no. 42
Sundin A, Arnold R, Baudin E, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Radiological, nuclear medicine & hybrid imaging. Neuroendocrinology 2017;105:212-44.  Back to cited text no. 43
Pezzilli R, Partelli S, Cannizzaro R, et al. Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review. Adv Med Sci 2016;61:147-53.  Back to cited text no. 44
Laskiewicz L, Jamshed S, Gong Y, et al. The diagnostic value of FNA biopsy in grading pancreatic neuroendocrine tumors. Cancer Cytopathol 2018;126:170-8.  Back to cited text no. 45
Larghi A, Capurso G, Carnuccio A, et al. Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by EUS-guided fine-needle tissue acquisition: A prospective study. Gastrointest Endosc 2012;76:570-7.  Back to cited text no. 46
Scarpa A, Mantovani W, Capelli P, et al. Pancreatic endocrine tumors: Improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 2010;23:824-33.  Back to cited text no. 47
Panzuto F, Boninsegna L, Fazio N, et al. Metastatic and locally advanced pancreatic endocrine carcinomas: Analysis of factors associated with disease progression. J Clin Oncol 2011;29:2372-7.  Back to cited text no. 48
Rindi G, Falconi M, Klersy C, et al. TNM staging of neoplasms of the endocrine pancreas: Results from a large international cohort study. J Natl Cancer Inst 2012;104:764-77.  Back to cited text no. 49
Bang JY, Hebert-Magee S, Navaneethan U, et al. Randomized trial comparing the Franseen and fork-tip needles for EUS-guided fine-needle biopsy sampling of solid pancreatic mass lesions. Gastrointest Endosc 2018;87:1432-8.  Back to cited text no. 50
Birnbaum DJ, Gaujoux S, Cherif R, et al. Sporadic nonfunctioning pancreatic neuroendocrine tumors: Prognostic significance of incidental diagnosis. Surgery 2014;155:13-21.  Back to cited text no. 51
Poultsides GA, Huang LC, Chen Y, et al. Pancreatic neuroendocrine tumors: Radiographic calcifications correlate with grade and metastasis. Ann Surg Oncol 2012;19:2295-303.  Back to cited text no. 52
Worhunsky DJ, Krampitz GW, Poullos PD, et al. Pancreatic neuroendocrine tumours: Hypoenhancement on arterial phase computed tomography predicts biological aggressiveness. HPB (Oxford) 2014;16:304-11.  Back to cited text no. 53
Palazzo M, Napoléon B, Gincul R, et al. Contrast harmonic EUS for the prediction of pancreatic neuroendocrine tumor aggressiveness (with videos). Gastrointest Endosc 2018;87:1481-8.  Back to cited text no. 54


  [Table 1], [Table 2]

This article has been cited by
1 Spatially resolved thermometry during laser ablation in tissues: Distributed and quasi-distributed fiber optic-based sensing
Federica Morra,Martina De Landro,Sanzhar Korganbayev,Alexey Wolf,Alexander Dostovalov,Alfredo Cigada,Paola Saccomandi
Optical Fiber Technology. 2020; 58: 102295
[Pubmed] | [DOI]
2 Endosonography guided ethanol ablation for pancreatic cystic lesions: Current status
Elia Armellini
Hepatobiliary & Pancreatic Diseases International. 2019;
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
   Radiofrequency A...
   Article Tables

 Article Access Statistics
    PDF Downloaded374    
    Comments [Add]    
    Cited by others 2    

Recommend this journal