Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook

Table 1 Characteristics and findings of studies of endoscopy-guided ablation for locally advanced pancreatic adenocarcinoma

Ref.	Year	No.	Endoscopy technique	Type of ablation	Stage of PDACn (%)	Median survival (mo)	Complications n (%)	Response rate n (%)
Chang et al[3]	2000	8	EUS-FNI	EUS-FNI Cytoimplant	4 (50) II 3 (37) III 1 (12.5) IV	13.2	8 (86) fever, 3 (37.5) GI toxicities, 3 (37.5) hyperbilirubinemia	3 (37) PR
Irisawa et al[85]	2007	7	EUS-FNI	EUS-FNI DCs	7 (100) IV	9.9	None	1 (14) CR 3 (43) PR
Hirooka et al[86]	2009	5	EUS-FNI	EUS-FNI DCs plus systemic GEM	5 (100) III	15.9	None	1 (20) PR
Hecht et al[4]	2003	21	EUS-FNI	ONYX-015 plus systemic GEM	3 (48) III 2 (52) IV	7.5	2 (10) sepsis, 2 (10) duodenal perforation, 2 (10) cystic fluid collection, 1 (5) fever	2 (10) PR
Hecht et al[87]	2012	50	EUS-FNI or percutaneous	TNFerade plus radiation and 5-FU	(100) III	13.2	6 (12) GI bleeding, 6 (12) deep vein thrombosis, 2 (4) pulmonary embolism, 9 (18) abdominal pain, 2 (4) pancreatitis, 1 (2) cholangitis	1 (2) CR 3 (6) PR
Herman et al[88]	2013	304	EUS-FNI or percutaneous	TNFerade plus radiation (180 pts) and 5-FU vs radiation and 5-FU (90 pts)	NR (Unresectable PDAC)	10 (the same in two groups) NR (7 pts alive at 6 mo and 2 at 12 mo)	34 (20) vs 10 (11) GI toxicities grade 3-4, 60 (33) vs 32 (35) hematologic toxicities grade 3-4, 22 (12) vs 7 (10), non-GI/nonhematologic toxicities (e.g., fever, fatigue) grade 3-4	8 (8.2) vs 6 (12) PR 3 PR
Hanna et al[89]	2012	9	EUS-FNI or percutaneous (TC-guided)	BC-819	8 (88.9) III 1 (10.1) IV		4 (44) gastrointestinal disorders, 2 (22) abdominal pain, 1 (11) influenza like illness, 1 (11) fatigue, 2 (22) back pain, 2 (22) hypertension 2 (22) metabolic disorders, 1 (11) syncope
Facciorusso et al[81]	2016	123	EUS-FNI	CPN plus ethanol (65 pts) vs CPN alone (58 pts)	25 (20.4) IV 98 (79.6) III	8.3 vs 6.5	16 (25) vs 14 (24) diarrhoea 31 (48) vs 11 (19) fever	NR
Waung et al[51]	2016	3	EUS-guided	RFA	3 (100) III	NR	30 (46) vs 20 (34) abdominal pain None	NR (14% mean reduction in size)
Song et al[48]	2016	6	EUS-guided	RFA	4 (67) III 2 (33) IV	NR	2 (33) abdominal pain	NR
Figueroa-Barojas et al[44]	2013	22	ERCP-guided	RFA	7 III plus 16 CHR 1 HGD IPMN	NR	5 (23) (1 pancreatitis post ERCP with cholecystitis, 5 abdominal pain)	NR
Kallis et al[45]	2015	69	ERCP-guided	RFA plus SEMS stenting (23 pts) vs SEMS stenting alone (46 pts)	100% III	7.5 vs 4.1	1 (1.4) cholangitis, 1 (1.4) asymptomatic hyperamylasaemia	NR

PDAC: Pancreatic ductal adenocarcinoma; EUS: Endoscopic ultrasound; ERCP: Endoscopic retrograde cholagiopancreatography; EUS-FNI: Endoscopic ultrasound fine-needle injection; RFA: Radiofrequency ablation; CHR: Cholangiocarcinoma; DCs: Dendritics cells; GEM: Gemcitabine; IPMN: Intraductal papillary mucinous neoplasia; SEMS: Self-expandable metal stent; NR: Not reported; CR: Complete response; PR: Partial response; 5-FU: 5-fluorouracil; CPN: Celiac plexus neurolysis; GI: Gastrointestinal; HGD: High grade dysplasia.

Table 2 Characteristics and findings of studies of endoscopic ultrasound-guided ablation of pancreatic neuroendocrine tumours

Ref.	Year	No.	Endoscopy technique	Type of ablation	Tumour typen (%)	Clinical response (mo)	Complications n (%)	Morphological response n (%)
Pai et al[8]	2015	2	EUS guided	RFA	2 NF-PNET	NR	2 abdominal pain	Complete necrosis of NF-PNET
Armellini et al[49]	2015	1	EUS guided	RFA	NF-PNET G2 (the patient refused surgery)	NR	No complications	CA on CT scan (one month later)
Lakhatia et al[50]	2016	3	EUS guided	RFA	Symptomatic insulinomas in patients unfit for surgery	All patients asymptomatic 12 mo after the procedure	No complications	1 disease free at 8 mo, 1 residual asymptomatic disease at 12 mo, 1 CA and asymptomatic at 11 mo
Waung et al[51]	2016	1	EUS-guided	3 consecutive RFA sessions	Symptomatic insulinoma (resistant to medical therapy)	Asymptomatic at 10 mo FU	No complications	NR
Levy et al[82]	2012	8	EUS-guided or intraoperative US (IOUS) guided	Ethanol	8 (100) insulinomas	5 patients asymptomatic, 3 clinical improvement	1 minor peritumoural bleeding (IOUS)	NR
Park et al[83]	2015	10 (13 tumours)	EUS-guided	Ethanol	10 NF-PNETs 4 insulinomas	2 asymptomatic pts with insulinomas	3 mild pancreatitis, 1 abdominal pain	13 (61.5) CA
Paik et al[84]	2016	8	EUS-guided	Ethanol	2 NF-PNETs, 3 insulinomas, 1 gastrinoma, 2 SPN	4 patients asymptomatic	1 severe acute pancreatitis, 2 abdominal pain, 1 fever	6 CA
Deprez et al[90]	2008	1	EUS-guided	Ethanol	1 insulinoma	Asynmptomatic	Ulceration of duodenal wall	CA
Jürgensen et al[6]	2006	1	EUS-guided	Ethanol	1 insulinoma	Asynmptomatic	1 mild acute pancreatitis	CA
Muscatiello et al[91]	2008	1	EUS-guided	Ethanol	1 insulinoma		1 pancreatic necroting lesion	CA

EUS: Endoscopic ultrasound; RFA: Radiofrequency ablation; MCN: Mucinous cystic lesions; IPMN: Intraductal papillary mucinous neoplasia; SPN: Solid pseudopapillary tumours; NET: Pancreatic endocrine tumour; NF-PNET: Non-functioning pancreatic neuroendocrine tumour; FU: Follow-up; NR: Not reported; CT: Computed tomography; CA: Complete ablation.

Table 3 Characteristics and findings of studies of endoscopic ultrasound-guided alcohol ablation in pancreatic cystic lesions

Ref.	Year	No.	Ablative agent	Clinical diagnosis (%)	Size mm (range)	Septated cysts n (%)	Follow-up months (range)	Complications	Percentage of ablated cysts
Gan et al[5]	2005	25	Ethanol	MCN 56%, IPMN 12%, SCA 12%, PCs 4%, unknown 8%	19.4 mean (6-37)	7 (28)	6-12	0%	35%
Oh et al[72]	2008	14	Ethanol and paclitaxel	MCN 14%, SCA 2%, lymphangioma 21%, unknown 43%	25.5 median (17-52)	3 (21.4)	9 median (6-23)	AP (7%)	79%
Oh et al[73]	2009	10	Ethanol and paclitaxel	MCN 30%, SCA 40%, unknown 30%	29.5 median (20-68)	10 (100)	8.5 median (6-18)	AP (10%)	60%
DeWitt et al[75]	2009	42	Ethanol vs saline	MCN 40%, IPMN 40%, SCA 12%, PCs 7%	20.5 (10-40)	17 (40.5)	3-4 mo after 2nd lavage	AP (2.4%), intracystic bleeding (2.4%), abdominal pain (24%), major complications, (24%)	33% (ethanol) 0% (saline)
Oh et al[74]	2011	52	Ethanol and paclitaxel	MCN 17%, SCA 29% PCs 4%, unknown 50%	31.8 (17-68)	20 (38.5)	21.7 mean (2-44)	Fever (2%), AP (2%), abdominal pain (2%), splenic vein obliteration (2%)	62%
DiMaio et al[76]	2011	13	Ethanol	IPMN 100%	20.1 mean (13-27.2)	7 (54)	3-6 mo after 2nd lavage	Abdominal pain (15%)	38%
Park et al[77]	2016	91	Ethanol	Indeterminate	30 (20-50)	64 (70)	40 median (13-117)	Fever (9%), abdominal pain (20%) AP (3%)	45%
Moyer et al[78]	2016	10	Ethanol or saline plus paclitaxel and gemcitabine	MCN 70%, IPMN 30%, unknown 10%	30	Unilocular predominantly	12	AP (10 %)	75% (ethanol plus paclitaxel and gemcitabine) 67% (alcohol free harm)

MCN: Mucinous cystic neoplasm; IPMN: Intraductal papillary mucinous neoplasm; SCA: Serous cystadenoma; PC: Pseudocyst; AP: Acute pancreatitis.