Endoscopic ultrasound-guided vascular interventions: An expanding paradigm

Table 1 Steps of endoscopic ultrasound-guided management (coil and glue combination) of Gastric varices

EUS-guided management of gastric varices using coil and glue combination
Pre-procedure requirements
All procedures are done under the cover of pre/peri-procedural antibiotics
Patient is usually kept fasting for 4-6 h before the procedure
Adequate resuscitation of the patient, in case of active bleeding is ensured, prior to the procedure
Informed consent prior to the procedure
What is needed prior to the procedure
Linear echoendoscope with at least a 3.7 mm working channel
Needle size: depends on the choice of the endoscopist; for > 10 mm coils, we need 0.035’ coil (19-G needle); can also use 0.018’ coil (22-G needle)
Diameter of the coils: 1.2-1.5 times the largest diameter of varix
Number of coils: depends on size of the varix
Amount of glue: depends on the size of the varix; but usually 2-4 mL is sufficient
Technical aspects
A proper diagnostic EUS is performed
The echoendoscope is usually positioned either in the distal esophagus or the gastric fundus
Saline is filled intra-luminally in the fundus to let the varices “float”. This enables a good acoustic coupling for better visualization of the gastric varices
Adequate examination of the fundus, the intramural varices and the feeder vessels is carried out
The approach can be trans-esophageal or trans-gastric, wherein the trans-esophageal route is given preference
Aim is to obliterate the intramucosal part of the varix
EUS-guided coil and glue embolization is usually performed using a 22-G/19-G (gauge) FNA needle
The size of the coil is determined by the short axis of the diameter of the varix
After puncture of the varix, blood is aspirated to confirm the location. This is followed by flushing of the needle with saline
The coils are then deployed into the varix using the stylet as a pusher. Once the coils are deployed, flushing of the needle is done with normal saline
After coil deployment, 1-2 mL of cyanoacrylate glue is injected followed by rapid flushing with saline
Once, the varix is obliterated, visualized by absence of flow on colour Doppler, the sheath of the needle is advanced beyond the endoscope tip for 2-3 cm before withdrawing the scope. This avoids contact of glue with the endoscope tip
Post procedure
The patients are kept under observation for 12 h
Repeat EUS can be done after 2 d to look for residual varices
Follow-up EUS to be performed at 1- and 3-mo intervals

EUS: Endoscopic ultrasound; FNA: Fine needle aspiration; G: Gauge.

Table 2 Existing literature on endoscopic ultrasound-guided vascular interventions for gastric varices

Ref.	Cases	Treatment used in EUS	EUS needle size	Number of coils (EUS only)	Use of Glue/others (mL) (EUS/endoscopic therapy)	Number of sessions (EUS/endoscopic)	Technical success (%)	Clinical success (%)	Adverse events (overall) (%)	Reintervention rates (%)	Rebleeding rates (%)	All-cause mortality (%)
Studies on only EUS-guided Glue injection
Lee et al[39], 2000	54	CYA (0.5 mL) with lipiodol (0.7 mL)	-	-	3 (1-8)	2.2 ± 1.7	52/54 (96.3%)	43/54 (79.6%)	22/54 (40.7%)	-	19/54 (35.2%)	28/54 (51.9%)
Romero-Castro et al[23], 2007	5	CYA-lipiodol (1 mL; 1:1)	22-G	-	1.6 (1-2)	2 cases: 1 each; 3 cases: 2 each	100%	100%	None	-	None	20%
Gubler and Bauerfeind[40], 2014	40	CYA-lipiodol (1 mL; 1:1)	22-G	-	1.9 (1-10)	1.4 (1-7)	40/40 (100%)	36/36 (100%)	2/40 (5%)	6/40 (15%)	-	6/40 (15%)
Studies on only EUS-guided coil injection
Romero-Castro et al[25], 2010	4	Coils	19-G	Each case: 22; 7; 3; 2	-	-	100%	3/4 (75%)	None	-	None	25%
Khoury et al[41], 2018	10	Coils	19-G	4.5 (mean)	-	2.8 (mean)	100%	complete (20%); near-complete (50%)	5 cases (minimal self-limited bleeding); 1 case needing blood transfusion	30% (3/10)	1 case (10%)	None
Studies on only EUS-guided coil + glue injection
Binmoeller et al[42], 2011	30	Coil + 1 mL CYA	19-G	-	1.4 (1-4)	1	30/30 (100%)	23/24 (95.8%)	None	1/30 (3.3%)	4/24 (16/6%)	1/30 (3.3%)
Bhat et al[27], 2015	152	Coil + 1 mL CYA	19/22-G	1.4 (1-4)	2 (0.5-6)	-	151/152 (99.3%)	93/100 (93%)	9/124 (7%)	7/125 (5.6%)	20/125 (16%)	3/151 (1.98%)
Kozieł et al[43], 2019	16	Coil + CYA (1:1 with lipiodol)	19-G	Total 21; mean 1.7 (1-3)	2 (1-9)	-	15/16 (94%)	Overall, 12/15 (75%) {coil+CYA (11/12 [92%]; only CYA [0%]}	6/16 (37.5%)	5/16 (31.3%)	1/16 (6.25%)	None
Robles-Medranda et al[44], 2019	30	Coil + CYA	19-G	2 (1-3)	1.8 (1.2-2.4 mL)	Mean 1.1	100%	96.6%	2 cases (6.7%)	3/27 (11.1%)	5 (16.7%)	4/30 (13.3%)
Kouanda et al[28], 2021	80	Coil + CYA	-	1.5 (1-3)	2 (0.5-5) mL	Mean 1.4	100%	60/62 (96.7%)	4 (4.9%)		6 (7.5%)	17 (21.3%)
Comparison of different treatment modalities for GV management
Romero-Castro et al[26], 2013	30	EUS-Coil (11) vs EUS-CYA (19)	19/22-G	5.8 (2-13) (overall 64 coils)	1.5 (1-3) (overall 29 mL)	Overall, 1.4 ± 0.1 (14 vs 29)	Overall, 27/30 (90%): 10/11 (90.9%) vs 17/19 (89.5%)	Overall, 29/30 (96.7%): 10/11 (90.9%) vs 19/19 (100%)	Overall, 12/30 (40%): 1/11 (9.1%) vs 11/19 (57.9%)	2/11 (18.1%) vs 9/19 (47.3%)	None (0 vs 0)	Overall, 6/30 (20%)
Bick et al[45], 2018	104	EUS-CYA (64) vs endoscopic CYA (40)	19/22-G	-	2 (0.8) vs 3.3 (1.3) mL	1 session (79% vs 75%); 2 sessions (21% vs 17.5%); 3 sessions (0% vs 7.5%)	100% vs 100%	49/64 (79%) vs 30/40 (75%)	13/64 (20.3%) vs 7/40 (17.5%)	-	5/57 (8.8%) vs 9/38 (23.7%)	-
Mukkada et al[32], 2018	81	EUS-coil +/- CYA (30) vs endoscopic CYA (51)	19-G	2.36 (mean) (total 71)	2 (1-10 mL) in 15 cases vs 3 ± 1.5 ml	Overall [42 vs 77]	100% vs 100%	8/20 (40%) vs (NA)	0% vs 0%	12/30 (40%) vs 26/51 (51%)	6/30 (20%) vs 26/51 (51%)	3/30 (10%) vs 2/51 (4%)
Robles-Medranda et al[29], 2019	60	EUS-coil + CYA (30) vs EUS-coil (30)	19-G	2 (1-3) vs 3 (1-7)	1.8 (1.2-2.4) vs -	-	100% vs 100%	30/30 (100%) vs 27/30 (90%)	2 (6.7%) vs 1 (3.3%)	5 (16.7%) vs 12 (40%)	1 (3.3%) vs 6 (20%)	9/30 (30%) vs 8/30 (26.7%)
Lôbo MRA et al[33], 2019	32	EUS-coil + CYA (16) vs endoscopic CYA (16)	19-G	Total 21	1.4 ± 0.74 vs 3.07 ± 1.94	Overall, 20 vs 18	100% vs 100%	11 (73.3%) vs 12 (75%)	8 (50%) vs 10 (62.5%)	4/15 (26.7%) vs 4/16 (25%)	2 (12.5%) vs 2 (12.5%)	0 (0%) vs 2 (12.5%)
Bazarbashi et al[46], 2020	40	EUS-coil + AGS (10) vs EUS/endoscopic CYA/histocryl (30)	19/22-G	8 ± 2.9	1.7 ± 2.9	-	10/10 (100%) vs 29/30 (96.7%)	100% vs 87%	1/10 (10%) vs 5/30 (20%)	1/10 (10%) vs 17/20 (56%)	0% vs 38%	1/10 (10%) vs 5/30 (16.6%)
Robles-Medranda et al[31], 2021	36	EUS-coil + CYA (17) vs endoscopic CYA (19)	19-G	0 vs 2 (1-3)	1.8 (1.2-2.4) vs 1.8 (0.6-6.6)	1 vs 1 (1-4)	17/17 (100%) vs 16/19 (84.2%)	-	2/17 (11.8%) vs 3/19 (15.8%)	-	0 vs 3/19 (15.8%)	-
Seven et al[47], 2022	28	EUS-coil (19) vs EUS-coil + CYA (9)	19-G	5 (3-9) vs 5 (3-9)	-	1 vs 1	19/19 (100%) vs 9/9 (100%)	19/19 (100%) vs 8/9 (88.9%)	1/19 (5.3%) vs 1/9 (11.1%)	1/19 (5.3%) vs 0/9 (0%)	1/19 (5.3%) vs 22.2%)	6/28 (21.42%)
Samanta et al[34], 2022 (Author’s centre)	170	EUS-coil+CYA (52) vs endoscopic CYA (118)	19-G	Median 2	2 (1) vs 2 (1) mL	1 (0) vs 2 (2)	52 (100%) vs 117 (99.2%)	-	0% vs 13.9%	7 (13.5%) vs 58 (49.6%)	8 (15.4%) vs 36 (31.3%)	-
Studies on EUS-guided treatment of GV using agents other than glue
Frost and Hebbar[36], 2017	8	Thrombin (1000 IU/5 mL; 2500 IU/5 mL)	22-G	-	For active bleeder: mean 7250 IU; for elective: mean 2520 IU	1 for each case	100% overall	Overall, 75% (active bleeder: 67%; elective cases: 80%)	None	None	None	1 case
Bazarbashi et al[37], 2019	10	Coil + AGS	19/22-G	8 ± 2.9	AGS: 2.5 ± 0.7	1 each	100%	9/9 (100%)	None	None	1/10 (10%)	None
Irisawa et al[38], 2020	8	Coil + sclerosant [EO]	19-G	5.6 ± 2.9	EO: 7.8 ± 6.7 mL	1.9 ± 1	100%	7/8 (87.5%)	None	-	-	-

EUS: Endoscopic ultrasound; G: Gauge; CYA: Cyanoacrylate; AGS: Absorbable gelatin sponge; EO: Ethanolamine oleate; IU: International units.

Table 3 Published literature on the use of endoscopic ultrasound-guided vascular interventions in ectopic varices

Ref.	Cases	Underlying diagnosis	Age/sex	Size of varix	Any prior therapy given	EUS therapy (agent used)	EUS needle used	Coils	Glue	Post procedure EUS findings	Follow-up duration	Comments
Duodenal varices
So et al[60], 2016	1	PC/EHPVO	65/F	2 cm	-	Coil	19-G FNA	3	-	Color Doppler: cessation of blood flow	10 mo	No bleeding on F/U
Kimura et al[61], 2017	1	PC	76/F	-	-	CYA glue	22-G FNA	-	0.5 mL (3 sessions)	- (f/u CT: shows extinction of contrast enhancement in DV)	6 mo	No bleeding on F/U
Kinzel et al[72], 2014	1	Cirrhosis (Child C)	31/M	10 mm	Endoscopic ethanolamine oleate	Coil + CYA glue	19-G (for coil) + 22-G (for glue) FNA	1	2 mL	Near complete thrombosis of varix	3 mo	No bleeding on F/U
Fujii-Lau et al[73], 2016	3	PVT; SMV-T; SMV-T	57/M; 46/F; 62/F	-; -; -	Glue; -; Clip + coil (IR)	Coil; Coil; Coil + CYA glue	22-G FNA (for all)	4; 4; 8	-; -; 2 mL	dec. flow; dec. flow; no flow	30 mo; 12 mo; 6 mo	No bleeding on F/U (all cases)
Bahdi et al[74], 2020	1	Cirrhosis	41/M	-	None	Coil + CYA glue	22-G FNA	8	2 mL	-	-	-
Rectal varices
Messallam et al[66], 2014	1	Cryptogenic cirrhosis	78/M	45 × 12 mm	None	Coil + CYA glue	19-G FNA	2	4 mL	No flow	12 wk	No bleeding on F/U
Sharma et al[67], 2010	1	PHTN	68/M	2.2 mm	None	Histocryl glue	-	-	1 mL	Decreased flow	6 mo	No bleeding on F/U
Mukkada et al[75], 2017	1	PHTN	65/M	5.9 mm	Endoscopic sclerotherapy (tetradecyl sulphate 16 ml; CYA glue)	Coil	19-G FNA	2	-	No flow	-	-
Bazarbashi et al[76], 2020	1	Cirrhosis	71/M	4 mm	None	Coil	19-G FNA	1	-	No flow	6 mo	No bleeding on F/U
Philips et al[77], 2017	1	Cirrhosis	48/M	-	None	Coil + CYA glue	22-G FNA	1	1 mL	No flow	1 mo	No bleeding on F/U
Weilert et al[78], 2012	1	Cirrhosis	60/F	> 3 cm	None	Coil + CYA glue	19-G FNA	5	4 mL	No flow	12 mo	No bleeding on F/U
Jana et al[79], 2017	1	Hepatitis C/PHTN	54/M	-	None	Coil + CYA glue	22-G FNA	3	0.8 mL	No flow	1 mo	No bleeding on F/U
Stomal varices
Tabibian et al[68], 2016	1	Cirrhosis PSC/post colectomy for UC	70/F	5 mm	Somatostatin/topical silver nitrate	Coil	22-G FNA	6	-	No flow	9 mo	No bleeding on F/U
Tsynman et al[69], 2014	1	UC/post colectomy/cirrhosis	74/F	-	TIPS	CYA glue with lipiodol	22-G FNA	-	0.5 mL	No flow	8 mo	No bleeding on F/U
Samanta et al[70], 2022	1	Alcohol cirrhosis/tubercular cocoon/ileostomy	52/M	-	Endoscopic glue injection	Coil + CYA glue	19-G FNA	2	4 mL	No flow	6 mo	No bleeding on F/U
Choledochal varices
Levy et al[71], 2008	1	CP/post total pancreatectomy	50/F	14 mm	-	Coil	22-G FNA	5	-	No flow	1 mo	No bleeding on F/u
Fujii-Lau et al[73], 2016	5	Cirrhosis; SMV-T; PVT; PHTN; PVT	61/M; 56/M; 27/M; 71/M; 50/F	-; -; -; -; -	None; None; None; None; None	Coil; Coil; Coil; Coil; Coil	22-G FNA (for all)	7; 9; 4; 5; 5	-; -; -; -; -	dec. flow; dec. flow; dec. flow; dec. flow; dec. flow	24 mo; 37 mo; 26 mo; 1 mo; 87 mo	Recurrent bleed in 3 cases; one case died due to underlying disease

EUS: Endoscopic ultrasound; PC: Pancreatic cancer; EHPVO: Extrahepatic portal vein obstruction; F: Female; M: Male; G: Gauge; FNA: Fine needle aspiration; F/U: Follow-up; CT: Computed tomography; DV: Duodenal varices; CYA: Cyanoacrylate; PVT: Portal vein thrombosis; SMV-T: Superior mesenteric vein thrombosis; IR: Interventional radiology; Dec.: Decreased; PHTN: Portal hypertension; PSC: Primary sclerosing cholangitis; UC: Ulcerative colitis; TIPS: Transjugular intrahepatic portosystemic shunt; CP: Chronic pancreatitis

Table 4 Steps for endoscopic ultrasound-guided management of visceral artery pseudoaneurysm

EUS-guided angioembolization of visceral artery pseudoaneurysm
Pre-procedure requirements
All procedures are done under the cover of pre/peri-procedural antibiotics
Patient is usually kept fasting for 4-6 h before the procedure
Adequate resuscitation of the patient, in case of active bleeding is ensured, prior to the procedure
Informed consent prior to the procedure
What is needed prior to the procedure
Linear echoendoscope with at least a 3.7 mm working channel
Needle size: depends on the choice of the endoscopist; usually a 19-G needle is used with 0.035’coil. However, a 22-G needle with 0.018’ coils may be used
Diameter of the coils: Smaller than the shortest diameter of the PsA
Number of coils: depends on size of the PsA
Amount of glue: depends on the size of the PsA
Technical aspects
A proper diagnostic EUS is performed
The echoendoscope is positioned optimally for a stable PsA access
Optimum examination of the PsA, the feeding vessel and the anatomy is delineated
The approach should always be through parenchyma, either pancreatic or hepatic. Bare puncture of the PsA without supporting parenchyma should not be performed
EUS-guided coil and glue embolization is usually performed using a 22-G/19-G (gauge) FNA needle
The size of the coil is determined by the short axis of the diameter of the PsA
After puncture of the varix, blood is aspirated to confirm the location. This is followed by flushing of the needle with saline. The pressure is high in the aneurysm, hence care should be taken to avoid creeping of blood along the hollow of the needle and causing needle block
The coils are then deployed into the varix using the stylet as a pusher. Packing with coils slows the flow inside the PsA, which can be visualized and further requirement of coils is assessed. Once the coils are deployed, flushing of the needle is done with normal saline
After coil deployment, cyanoacrylate glue is injected using the coils as scaffold
Once, the PsA is obliterated, visualized by absence of flow on colour Doppler, the sheath of the needle is advanced beyond the endoscope tip for 2-3 cm before withdrawing the scope. This avoids contact of glue with the endoscope tip
Post procedure
The patients are kept under observation for 12 h
Post embolization X-ray would help visualize the coils and also look for complications
Repeat EUS can be done after 48 hrs. to look for residual flow
Cross-sectional imaging is usually done after 72 h. to document success of therapy
Follow-up EUS may be performed at 1-mo

G: Gauge; PsA: Pseudoaneurysm; EUS: Endoscopic ultrasound; FNA: Fine needle aspiration.

Table 5 Published case series on endoscopic ultrasound-guided angiotherapy for arterial pseudoaneurysm

S.No.	Ref.	Cases	Age/sex	Chief complaints	Artery involved	PSA size (mm)	EUS needle used	Embolization agent used	EUS sessions needed	Technical/clinical success	Complications	Follow up and comments
1	Gamanagatti et al[91], 2015	3	56/M; 45/M; 30/M	Upper GI bleed (all 3)	GDA; Splenic; Splenic	-	22-G	Thrombin (500 IU, 300 IU, 400 IU)	1 each	Yes/yes	None	Imaging F/U: complete obliteration; no bleeding at 1 mo F/U
2	Jhajharia et al[92], 2018	3	43/M; 25/M; 55/M	Pain abdomen; hematemesis; Malena (respectively)	GDA; Right hepatic; splenic	40 × 50; 30 × 22 × 27; 15 × 13	22-G	Thrombin (1000 IU; 1000 IU; 500 IU)	1 each	Yes/yes	None	F/U at 1.5 years, 1 year and 3 mo: no bleeding (respectively)
3	Rai et al[93], 2018	6	Median 36.7 years (19-60); 5 men	3 asymptomatic; 3 upper GI bleed	All Splenic artery PSA	25-65 (range)	19-G	Coils (size 8, 14, 16; number 1-5) and glue (1-2 mL)	3 cases needed 2 EUS sessions (size > 4 cm)	Yes/yes (all cases)	None	EUS (4 wk) and CT (3 mo): complete obliteration
4	Maharshi et al[94], 2020	8	Median 34 years (27-58); all males	Malena (100%); hematemesis (75%)	Splenic (5); left hepatic (2); GDA (1)	Median 29 × 26 (range 18 × 19 – 40 × 50)	22-G	Thrombin (200-500 IU)	1	Yes/87.5% clinical success (7/8 cases)	2 cases post procedural pain	EUS (1 and 3 mo) and CT (1 mo): complete obliteration; only 1 case with PSA > 5 cm needed second EUS session after 6 wk
5	Samanta et al[95], 2022	16 PsA (in 15 patients)	Median 44 (17-56); males 14 (93.3%)	Malena/ incidental/ PCD bleed	Splenic (12); GDA (4)	Median 2.8 (0.9-9.7 cm)	19-G	Coils (median 1[1-8]) with CYA glue (median 2 [1-5 mL])	1 session in 15 (93.8%)	Yes/yes	One case had splenic infarct (managed conservatively)	Follow-up at 6 mo: no rebleed; one case developed recurrent PsA at a site separate from first PsA (managed again with EUS)

PsA: Pseuoaneurysm; EUS: Endoscopic ultrasound; F/U: Follow-up; IU: International units; GDA: Gastroduodenal artery; PCD: Percutaneous catheter drainage; CYA: Cyanoacrylate glue; GI: Gastrointestinal; CT: Computed tomography.

Table 6 Technique for assessing endoscopic ultrasound-guided portal pressure gradient

Procedural steps for measuring EUS-PPG
The measurement of PPG via EUS requires 4 components: 25-G FNA needle, non-compressible tubing, a compact digital manometer, and heparinized saline. The tubing is connected by a luer lock to the distal port and heparinized saline is connected the proximal port of the manometer
With the patient supine, the manometer is placed at the patient’s midaxillary line
The HV measurement is conducted first, in which middle HV is targeted most often (larger calibre and better alignment with the needle trajectory). Then PV measurement is taken (umbilical portion of left PV is the target)
Doppler flow is used to confirm the typical multiphasic waveform of hepatic venous flow and typical venous hum of the portal venous flow
Trans-gastric trans-hepatic route is taken for HV and PV puncture
Needle is flushed with heparinized saline (1 mL). The steadiest reading at equilibrium is recorded. Three measurements are taken and their mean is calculated (both HV and PV pressures)
The FNA needle is slowly withdrawn from the vein into the liver parenchyma and then back into the needle sheath with Doppler flow on to ensure there is no flow within the needle tract

EUS: Endoscopic ultrasound; PPG: Portal pressure gradient; G: Gauge; FNA: Fine needle aspiration; PV: Portal vein; HV: Hepatic vein.

Table 7 Published literature (human studies) on the use of endoscopic ultrasound-guided portal pressure measurement

Ref.	Year	Number of cases	Approach	EUS-FNA needle	Technical success	Complications	Correlation between EUS and trans-hepatic PVP measurement
Fujii-Lau et al[106]	2014	1	Trans-gastric	22-G	1	None	PPG 1 mmHg (excellent correlation with HVPG)
Huang et al[105]	2017	28	-	25-G	25/25 cases	None	Excellent correlation with varices (P = 0.0002), PHG (P = 0.007), and thrombocytopenia (P = 0.036); few of them also underwent liver biopsy in same setting
Zhang et al[107]	2020	12	-	22-G	11/12 cases (91.7%)	None	R = 0.923
Shah et al[109]	2021	1	Trans-gastric	25-G	1	None	NA (same session EUS-liver biopsy was done)
Hajifathalian et al[108]	2021	24	Trans-gastric	25-G	23/24 (96%) patients also underwent EUS-liver biopsy (TS: 24/24 [100%])	One case of mild abdominal pain (resolved with analgesics)	NA; excellent correlation with fibrosis-4 score (P = 0.026) and transient elastography (P = 0.011)
Choi et al[110]	2022	83	Trans-gastric	25-G	100%; 71 cases underwent EUS-liver biopsy	No major events; minor abdominal pain (8 [9.6%] cases)	Correlation with clinical features of cirrhosis (9.46 vs 3.61 mmHg, P < 0.0001), EV/GV (13.88 vs 4.34 mmHg, P < 0.0001), and thrombocytopenia (9.25 vs 4.71 mmHg, P = 0.0022)
Choi et al[111]	2022	64	Trans-gastric	25-G	100% (concurrent EUS-LB in 43/64 [67.2%])	1 case (EUS-PPG alone); 5 cases (EUS-PPG + EUS-LB both)	EUS-PPG > 5 mmHg correlated with EUS-liver biopsy fibrosis stage ≥ 3 [LR 27] (P = 0.004)

EUS: Endoscopic ultrasound; PPG: Portal pressure gradient; FNA: Fine needle aspiration; PVP: Portal venous pressure; G: Gauge; LB: Liver biopsy; EV: Esophageal varices; GV: Gastric varices; LR: Likelihood ratio; NA: Not available; PH: Portal hypertensive gastropathy.