Endoscopic ultrasound role in pancreatic adenocarcinoma treatment: A review focusing on technical success, safety and efficacy

Table 1 Human studies reporting endoscopic ultrasound-guided intra-tumoral injection therapies

Ref.	Study design	Cancer stage	EUS-guided intervention	Patients No.	Technical success (%)	Median overall survival (mo)	Pain palliation	Serious adverse events, n
Levy et al[9], 2017	Prospective	II (n = 3); III (n = 20); IV (n = 13)	Chemotherapy	36	100	10.4	Not reported	0
Chang et al[10], 2000	Prospective	II (n = 4); III (n = 3); IV (n = 1)	Immunotherapy	8	100	13.2	Not reported	0
Irisawa et al[11], 2007	Prospective	IV (n = 7)	Immunotherapy	7	100	9.9	Not reported	0
Endo et al[12], 2012	Prospective	II (n = 1); III (n = 5); IV (n = 3)	Immunotherapy	9	100	18	Not reported	31
Buscail et al[23], 2015	Prospective	III (n = 13); IV (n = 9)	Gene therapy	22	100	12.6	Not reported	0
Hecht et al[14], 2003	Prospective	III (n = 9); IV (n = 21)	Gene therapy	21	100	7.5	Not reported	42
Hecht et al[16], 2012	Prospective	III (n = 27)	Gene therapy	27/50	100	9.9	Not reported	403
Herman et al[17], 2013	Prospective	III (n = 95)	Gene therapy	95/187	100	11.5	Not reported	484
Hanna et al[18], 2012	Prospective	Unresectable	Gene therapy	6	100	6	Not reported	15
Hirooka et al[20], 2018	Prospective	III (n = 9)	Gene therapy	9	100	15.5	Not reported	26
Nishimura et al[22], 2018	Prospective	III (n = 5); IV (n = 1)	Gene therapy	6	100	5.8	Not reported	0
Golan et al[25], 2015	Prospective	III (n = 15)	Intra-tumoral implantation	15	100	15.1	Not reported	47

¹Pancreatic fistula (2 patients) and superior mesenteric artery pseudoaneurysm (1 patient).

²Sepsis (2 patients), duodenal perforations (2 patients).

³The authors did not state whether these adverse events were in the endoscopic ultrasound (EUS) group or in the percutaneous group: Gastrointestinal bleeding (6 patients), deep vein thrombosis (6 patients), pulmonary embolism (2 patients), pancreatitis (2 patients), cholecystitis (1 patient), biliary obstruction (8 patients), cholangitis (6 patients), hypotension (2 patients), bradycardia (1 patient), supraventricular tachycardia (1 patient), splenic artery thrombosis (1 patient), intestinal ischemia (1 patient), staphylococcus infection (1 patient), cerebrovascular accident (1 patient), cardio-pulmonary arrest (1 patient).

⁴The authors did not state what are the serious adverse events and whether these adverse events were in the EUS group or in the percutaneous group.

⁵Hypoglycemia (1 patient).

⁶Perforation of duodenum (1 patient) and hepatic dysfunction 1 patient), but these events were considered not to be related.

⁷Colonic obstruction (1 patient), pancreatitis (1 patient), cholangitis (1 patient), renal failure (1 patient).

Table 2 Human studies reporting endoscopic ultrasound-guided ablation therapies

Ref.	Study design	Cancer stage	EUS-guided intervention	Patients No.	Technical success (%)	Median overall survival (mo)	Pain palliation (patients %)	Serious adverse events, n
Facciorusso et al[31], 2017	Prospective	III (n = 50); IV (n = 15)	Ethanol ablation	65	100	8.3	90.7 at week 2	0
Song et al[35], 2016	Prospective	III (n = 4); IV (n = 2)	RFA	6	100	-1	Not reported	0
Crinò et al[36], 2018	Prospective	III (n = 8)	RFA	8	100	-1	Not reported	0
Scopelliti et al[37], 2018	Prospective	III (n = 10)	RFA	10	100	-1	Not reported	0
Paiella et al[38], 2018	Retrospective	Not reported	RFA	30	100	15	Not reported	0
Bang et al[39], 2019	Prospective	II (n = 2); III (n = 3); IV (n = 7)	RFA	12	100	Not reported	Significant	0
Arcidiacono et al[41], 2012	Prospective	III (n = 22)	HCA	22	72.8	6	Not reported	12
DeWitt et al[45], 2019	Prospective	III (n = 12)	PDA	12	100	11.5	Not reported	0
Di Matteo et al[46], 2018	Prospective	III (n = 9)	Laser ablation	9	100	7.4	Not reported	0

¹Feasibility studies not aimed to assess impact on overall survival.

²Minor bleeding in duodenal lumen successfully stopped by hemoclips (1 patient). RFA: Radiofrequency ablation; HCA: Hybrid cryothermal ablation; PDA: Photodynamic ablation; EUS: Endoscopic ultrasound.

Table 3 Human studies reporting endoscopic ultrasound-guided fiducial markers placement, -brachytherapy and -celiac plexus neurolysis

Ref.	Study design	Cancer stage	EUS-guided intervention	Patients No.	Technical success (%)	Median overall survival (mo)	Pain palliation (patients %)	Serious adverse events, n
Pishvaian et al[48], 2006	Prospective	Unresectable	FMP	7	85.7	-1	Not reported	0
Choi et al[49], 2014	Prospective	Unresectable	FMP	29	100	-1	Not reported	12
Varadarajulu et al[50], 2010	Prospective	III (n = 9)	FMP	9	100	Not reported	Not reported	0
Park et al[51], 2010	Prospective	III (n = 57)	FMP	57	94	-1	Not reported	0
Sanders et al[52], 2010	Prospective	III (n = 36); Recurrent (n = 15)	FMP	51	90	-1	Not reported	12
Dávila et al[53], 2014	Prospective	II (n = 1); III (n = 22)	FMP	23	100	-1	Not reported	0
Khashab et al[54], 2012	Retrospective	III (n = 39)	FMP	39	100	-1	Not reported	0
Sun et al[57], 2012	Prospective	III (n = 8)	Brachytherapy	8	100	8.3	50 at week 33	0
Sun et al[58], 2006	Prospective	III (n = 8); IV (n = 7)	Brachytherapy	15	100	10.6	30 at week 42	33
Jin et al[59], 2008	Prospective	II (n = 4); III (n = 10); IV (n = 8)	Brachytherapy	22	100	9	81.8 at week 1	0
Sun et al[60], 2017	Retrospective	III (n = 18); IV (n = 24)	Brachytherapy	42	100	9	Not reported	0
Wiersema et al[62], 1996	Prospective	Unresectable	CPN	29	100	Not reported	86 at week 2; 84 at week 4; 79 at week 8; 88 at week 12	0
Levy et al[64], 2019	Prospective	II (n = 2); III (n = 27); IV (n = 31)	CPN	60	100	10.46	40.4 at week 12	0
Seicean et al[65], 2013	Prospective	Unresectable	CPN	32	100	Not reported	75 at week 2	0
Facciorusso et al[31], 2017	Prospective	III (n = 48); IV (n = 10)	CPN	58	100	6.5	70.6 at week 2	0

¹Feasibility studies not aimed to assess impact on overall survival.

²Pancreatitis supportively treated (1 patient).

³Pancreatitis complicated with pseudocyst formation (3 patients).

FMP: Fiducial markers placements; CPN: Celiac plexus neurolysis; EUS: Endoscopic ultrasound.

Table 4 Summary of efficacy and safety of endoscopic ultrasound-guided angio-therapy procedures

Procedure	Intra-tumoral injection therapies	Ablation therapies	Fiducial markers placement, brachytherapy and celiac plexus neurolysis
Technical success	High	High	High
Safety (complications)	Uncertain1	Minor	Minor
Efficacy
Survival	Modest	None	None
Palliation	Not reported	Encouraging	High
Mortality	None	None	None

¹The two studies that had the highest adverse events rate did not state whether they were in the endoscopic ultrasound or in the percutaneous group. See Table 1.