Endoscopic ultrasound guided radiofrequency ablation for pancreatic tumors: A critical review focusing on safety, efficacy and controversies

Table 1 Studies reporting endoscopic ultrasound-radiofrequency ablation for pancreatic neuroendocrine neoplasms

Ref.	Type of study (pNEN type)	Patients/lesions/RFA sessions, n	Location, n	Mean size (range) in mm	Histological grade (KI67%)	Technical success, n (%)	Adverse events, n (%)	Complete radiological/ clinical1 resolution, n (%)	Mean follow-up in mo
Rossi et al[10]	Case report (nonfunctional)	1/1/1	Head (1)	10	NR	1 (100)	0	1 (100)	34
Armellini et al[11]	Case report (nonfunctional)	1/1/1	Tail (1)	20	G2 (> 5)	1 (100)	0	1 (100)	1
Lakhtakia et al[12]	Case series (insulinoma)	3/3/3	Body (2), diffuse (1)	17.7 (14-22)	NR	3 (100)	0	3 (100)/3 (100)	4.2
Waung et al[21]	Case report (insulinoma)	1/1/3	Uncinate (1)	18	NR	1 (100)	0	1 (100)/1 (100)	10
Bas-Cutrina et al[22]	Case report (insulinoma)	1/1/1	Body (1)	10	NR	1 (100)	0	1 (100)/1 (100)	10
Pai et al[23]	Prospective (nonfunctional)	2/2/3	Head (1)	27.5 (15-40)	NR	2 (100)	0	2 (100)	6
Barthet et al[13]	Prospective (nonfunctional)	12/14/12	Head (3), body (6), tail (5)	13.1 (10-20)	G1	12 (100)	2 (16.7)2	9 (75)	12
Choi et al[25]	Prospective (nonfunctional-7), (insulinoma-1)	8/8/14	Head (3), body (5)	19.25 (8-28)	Reported in 2 patients (G1 and G2)	8 (100)	2 (14.3)3	6 (75)/1 (100)	13
de Nucci et al[26]	Prospective (nonfunctional)	10/11/10	Head (3), body (8), tail (2)	14.5 (9-20)	G1 (< 4)	10 (100)	2 (20)4	10 (100)	12
Oleinikov et al[14]	Retrospective (nonfunctional-11), (insulinoma-7)	18/27/18	Head (10), body (8), tail (2), uncinate (5), metastasis (2)	14.8 (12-19)	G1 (< 5) in 15 patents, G3 (34-40) in 2 patients	18 (100)	2 (11.1)5	17 (94.4)/7 (100)	8.7
Rossi et al[30]	Case series (insulinoma)	3/3/4	NR	11.5 (9-14)	NR	3 (100)	1 (25)6	3 (100)/3 (100)	8.5
Chang et al[27]	Case report (insulinoma)	1/1/1	Head (1)	12	NR	1 (100)	0	1 (100)/1 (100)	18
Kluz et al[28]	Case report (insulinoma)	1/1/1	Head (1)	9	NR	1 (100)	1 (100)7	NR/1 (100)	NR
Furnica et al[29]	Case series (insulinoma)	4/4/4	Head (2), neck (1), tail (1)	12.9 (6.5-22.0)	G1 in 3 patients and G2 in 1 patient	4 (100)	2 (50)8	4 (100)/4 (100)	22
Marx et al[15]	Retrospective (insulinoma)	7/7/7	Head (1), body (1), neck (3), body-tail junction (2)	13.3 (8-20)	G1 (< 3) in 4 patient, G2 (4) in 1 patient	7 (100)	4 (57.1)9	6 (85.7)/7 (100)	20.3
Marx et al[31]	Retrospective (non-functional)	27/27/31	Head (6), body (3), tail (11), uncinate (2), body-tail junction (5)	14 (7-25)	G1 (< 3) in 25 patients, NR in 2 patients	27 (100)	9 (29)10	25 (92.6)	15.7
Pooled data	Case reports: 9. Prospective: 4. Retrospective: 3	100/112/114	Head and neck (33), body (34), tail (22), uncinate (8), metastasis and diffuse (3), junction (7)	14.8	Unable to pool due to data lacking	96 (100)	25 (21.9)	90 (90)/21 (100)	13

¹Insulinoma.

²Infected pancreatic necrosis (1 patient, moderate), pancreatic duct stenosis (1 patient, moderate).

³Pancreatitis (1 patient, moderate), transient abdominal pain (1 patient, mild).

⁴Transient abdominal pain (2 patients, mild).

⁵Pancreatitis (2 patients, mild).

⁶Intraprocedural bleeding treated endoscopically (1 patient, moderate).

⁷Acute necrotizing pancreatitis (1 patient, moderate).

⁸Pancreatitis (2 patients, mild).

⁹Transient abdominal pain (1 patient, mild), pancreatitis (1 patient, moderate), coagulation necrosis (1 patient, moderate), retrogastric collection (1 patient, refused drainage, died 2 wk later, severe).

¹⁰Transient abdominal pain (3 patients, mild), pancreatitis (1 patient, moderate), periprocedural bleeding (2 patients, moderate), pancreatitis complicated by retrogastric or perisplenic collection managed by endoscopic drainage and antibiotic treatment (2 patients, moderate), pancreatitis with pancreatic fistula and paragastric collection drained by endoscopic cystgastrostomy (1 patient, moderate).

pNEN: Pancreatic neuroendocrine neoplasms; NR: Not reported; RFA: Radiofrequency ablation.

Table 2 Studies reporting endoscopic ultrasound-radiofrequency ablation for pancreatic adenocarcinoma

Ref.	Study type	Patients/RFA session, n	Tumor location (n)	Cancer stage (n)	Mean size (range) in mm	Any decrease in tumor size, n (%)	Technical success, n (%)	Adverse events, n (%)	Mean follow-up in mo	Survival after RFA in mo
Arcidiacono et al[16]	Prospective	22/22	Head (16), uncinate (2), body (4)	Locally advanced (22)	35.7 (23-54)	6 (37.5)	16 (72.7)	8 (36.4)1	3	5.6 (1-12)
Song et al[32]	Prospective	6/8	Head (4), body (2)	Locally advanced (4), metastasis (2)	48 (30-90)	NR	6 (100)	2 (25)2	4.2	NR
Scopelliti et al[17]	Prospective	10/10	Head (4), body (6)	Locally advanced (10)	49.2 (25-75)	10 (100)	10 (100)	4 (40)3	1	NR
Crinò et al[18]	Retrospective	7/7	Head (2), body (3), uncinate (2)	Locally advanced (7)	36 (22-67)	7 (100)	7 (100)	3 (42.8)4	6.1	NR
Paiella et al[19]	Retrospective	30/30	Head (23), body and tail (7)	Locally advanced (30)	35 (20-60)	NR	30 (100)	1 (3.3)5	15	15
Bang et al[20]	Prospective	12/12	Head and uncinate (8), body and tail (4)	Locally advanced (5), metastasis (7)	29.6 (22.5-35.0)	NR	12 (100)	5 (41.6)6	1	NR
Wang et al[33]	Retrospective	11/26	Head (4), neck (3), body (3), tail (1)	Locally advanced (7), metastasis (4)	28 (17.2-38)	2 (18.2)	11 (100)	2 (7.7)7	5.2	5.2
Oh et al[34]	Prospective	22/107	Head (14), body (4), tail (3), metastasis (1)	Locally advanced (14), metastatic (8)	38 (32.8-45.0)	NR	22 (100)	4 (3.7)8	21.2	24
Pooled data	Prospective: 5. Retrospective: 3	120/222	Head and uncinate (79). Body and tail (37), neck (3)	Locally advanced (100), metastasis (21)	37.4	Unable to pool due to data lacking	114 (95)	29 (13)	7.1	Unable to pool due to data lacking

¹Transient abdominal pain (3 patients, mild), minor duodenal bleeding endoscopically treated (1 patient, moderate), transient amylase elevation (3 patients, mild), transient cystic fluid collection between pancreas and left hepatic lobe (1 patient, mild).

²Transient abdominal pain (2 patients, mild).

³Mild pancreatitis (4 patients, mild).

⁴Transient abdominal pain (3 patients, mild).

⁵Duodenal bleeding (1 patient, moderate).

⁶Nausea and vomiting (4 patients, mild), transient abdominal pain (1 patient, mild).

⁷Transient abdominal pain (2 patients, mild).

⁸Transient abdominal pain (3 patients, mild), peritonitis (1 patient, moderate).

NR: Not reported; RFA: Radiofrequency ablation.

Table 3 Studies reporting endoscopic ultrasound-radiofrequency ablation for pancreatic cystic tumors

Ref.	Type of study	Patients/RFA sessions, n	Type of cyst	Mean size (range) in mm	Worrisome features	Technical success, n (%)	Adverse events, n (%)	Complete/partial resolution, n (%)	Mean follow-up in mo
Pai et al[23]	Prospective	6/6	MCN (4), IPMN (1), MCA (1)	41 (24-70), 35, 20	NR	6 (100)	2 (33.3)1	2 (33.3)/4 (66.7)	6
Choi et al[25]	Prospective	2/2	SPT (2)	21.5 (20-23)	NR	2 (100)	0	1 (50)/1 (50)	13
Barthet et al[13]	Prospective	17/17	MCN (1), IPMN (16)	28 (9-60)	16 (94.1)	17 (100)	1 (5.9)2	11 (64.7)/1 (5.9)	12
Oh et al[36]	Retrospective	13/19	SCN (13)	50 (34-52.5)	NR	13 (100)	1 (5.3)3	0/8 (61.5)	9.2
Pooled data	Prospective: 3. Retrospective: 1	38/44	MCN (5), IPMN (17), MCA (1), SPT (2), SCN (13)	32.1	Unable to pool due to data lacking	38 (100)	4 (9.1)	14 (36.8)/14 (36.8)	10.2

¹Transient abdominal pain (2 patients, mild).

²Fever and pneumoperitoneum with fluid collection and jejunal loop perforation needed surgery (1 patient, severe).

³Transient abdominal pain (1 patient, mild).

IPMN: Intraductal papillary mucinous neoplasm; MCA: Microcystic adenoma; MCN: Mucinous cystic neoplasm; NR: Not reported; RFA: Radiofrequency ablation; SPT: Solid pseudopapillary tumor; SCN: Serous cystic neoplasm.

Table 4 Pooled analysis of the adverse events

EUS-guided RFA for	Procedure-related adverse events according to ASGE[9]1
	Mild, n (%)	Moderate, n (%)	Severe, n (%)	Mortality, n (%)
Neuroendocrine neoplasms EUS-RFA sessions = 114	11 (9.6)	13 (11.4)	1 (0.9)	1 (0.9)
Adenocarcinoma EUS-RFA sessions = 223	26 (11.6)	3 (1.3)	0	0
Cystic tumors EUS-RFA sessions = 44	3 (6.8)	0	1 (2.3)	0
Pooled data	40 (10.5)	16 (4.2)	2 (0.5)	1 (0.26)

¹Overall, 380 EUS-RFA sessions performed for all pancreatic tumors.

ASGE: American Society of Gastrointestinal Endoscopy; EUS-RFA: Endoscopic ultrasound-radiofrequency ablation.

Table 5 Summary of efficacy and safety of endoscopic ultrasound-guided radiofrequency ablation for pancreatic tumors

Procedure	EUS-guided RFA for pancreatic
	Neuroendocrine tumors	Adenocarcinoma	Cystic tumors
Technical success	High	High	High
Safety, complications	Mild-moderate1	Mild	Mild
Efficacy
Clinical improvement	Significant for insulinomas	None	-
Radiological partial/complete resolution	High	Modest	Encouraging
Palliation	-	Encouraging	-
Mortality	None	None	None

¹When taking prophylactic measures (antibioprophylaxis, fluid component suction before radiofrequency ablation).

EUS-RFA: Endoscopic ultrasound-radiofrequency ablation.

Table 6 Technical considerations and imaging studies used in follow-up among patients with pancreatic neuroendocrine neoplasms

Ref.	Number of patients/sessions	Power setting in Watts	RFA application number in all sessions	Imaging study used in radiological follow-up
Rossi et al[10]	1/1	10-15	1	CECT or MRI
Armellini et al[11]	1/1	NR	2	CT and CE-EUS
Lakhtakia et al[12]	3/3	50	9	CECT (1 patient), CECT and EUS (2 patients)
Waung et al[21]	1/3	10	25	CT and gallium dotatate positron emission tomography
Bas-Cutrina et al[22]	1/1	10	3	NR
Pai et al[23]	2/3	20	10	Cross sectional imaging not stated which
Barthet et al[13]	12/12	50	NR	CT and EUS
Choi et al[25]	8/14	50	65	CECT and CE-EUS
de Nucci et al[26]	10/10	20	23	CT
Oleinikov et al[14]	18/18	50	3-10 in each EUS-RFA session	CECT (9 patients), NA (5 patients), CECT and somatostatin receptor imaging (3 patients)
Rossi et al[30]	3/4	30	14	EUS (1 patient), MRI (1 patient), refused follow-up (1 patient)
Chang et al[27]	1/1	50	2	CECT
Kluz et al[28]	1/1	50	3	NR
Furnica et al[29]	4/4	50	1-3 per each EUS-RFA	CT
Marx et al[15]	7/7	50	1-5 for each EUS-RFA session	CE-EUS or MRI
Marx et al[31]	27/31	50	1-5 for each EUS-RFA session	CT or MRI

CE-EUS: Contrast enhanced endoscopic ultrasound; CECT: Contrast enhanced computed tomography; CT: Computed tomography; EUS-RFA: Endoscopic ultrasound-radiofrequency ablation; MRI: Magnetic resonance imaging; NA: Not available; NR: Nor reported.

Table 7 Clinical and radiological follow-up in pancreatic insulinomas studies

Ref.	Patients with insulinoma, n	Mean time (range) of clinical follow-up in mo	Mean time (range) of radiological follow-up in mo
Lakhtakia et al[12]	3	11.7 (11-12)	4.2 (1.5-8)
Waung et al[21]	1	10	3 d
Bas-Cutrina et al[22]	1	10	10
Choi et al[25]	1	NR	NR
Oleinikov et al[14]	7	9.7 (3-21)	8.7 (2-21)
Rossi et al[30]	3	22 (14-27)	5.7 (3-14)
Chang et al[27]	1	18	18
Kluz et al[28]	1	NR	NR
Furnica et al[29]	4	22 (13-28)	8 (3-14)
Marx et al[15]	7	21 (3-38)	20.3 (3-38)

NR: Not reported.