Endoscopic Variceal Ligation: A to Z

Division of Gastroenterology and Hepatology, Liver Clinic

Department of Internal Medicine

Soon Chun Hyang University School of Medicine,

Soon Chun Hyang University Bucheon Hospital, Bucheon, Korea

김 상 균

Agenda

1. Endoscopic classification of esophageal varices

2. Endoscopic ultrasound for the management of

esophageal varices

3. Endoscopic treatment of esophageal varices

1) Endoscopic injection sclerotherapy (EIS) vs. Endoscopic variceal

ligation (EVL)

2) Primary prophylaxis for esophageal varices

3) Acute esophageal bleeding

4) Secondary prophylaxis after variceal bleeding

4. Procedure of endoscopic band ligation

5. Recurrence of esophageal varices after band ligation

6. Conclusions

Case • 52/M, Chronic alcoholism

• C/C : Abdominal distension, 1 month ago

• MELD score:22, Child-Pugh class C with ascites

• endoscopy

What should be recorded?

1. F2, Lm, Cb, red wale marking, hematocystic spots

2. F3, Lm, Cb, RC (++),

3. F2, Lm, RC (++)

4. F3, RC (++)

5. F1, RC

Endoscopic Classification According to Form

F0: No varicose appearance

F1: Straight, small-caliber varices

F2: Moderately enlarged, beady varices

F3: Markedly enlarged, nodular or tumor-shaped varices

The Japanese Research Society for Portal Hypertension. Dig Endosc 2010;22:1-229

Endoscopic Classification According to Color

• Cw: White varices Cb: Blue varices

• Cw-Th: Thrombosed white varices

• Cb-Th: Thrombosed blue varices

Endoscopic Classification According to Location

• Ls: Locus superior

• Lm: Locus medialis

• Li: Locus inferior

• Lg-c: Adjacent to the cardiac orifice

• Lg-cf: Extension from the cardiac orifice to the fornix

• Lg-f: Isolated in the fornix

• Lg-b: Located in the gastric body

• Lg-a: Located in the gastric antrum

Modified from Sohendra N, et al. Therapeutic Endoscopy

Endoscopic Classification According to Red Color Sign

• Red wale markings, Cherry red spots, Hematocystic spots,

• RC0: absent, RC1: small in No & localized, RC2: RC1 - RC 3,

RC3: large in No and circurmferential

Endoscopic findings and scoring system predicting variceal bleeding

• By Japansese Research Society for Portal Hypertension;

• Validated by North Italian Endoscopic Club

Beppu K, Gastrointest Endoscopy, 1981;27:213-8

Risk Class

Beppu’s Score

No.Who

Bled/Total

Rate of Bleeding(%)

Expected Observed

1yr 2yr

1 >+1.14 7/61 0.0 3.4 9.2

2 0.38 to 1.14 35/146 20.6 14.9 22.1

3 <0.38 to 0.0 6/12 40.0 25.1 33.3

4 0.0 to >-0.38 13/50 64.5 16.7 29.0

5 -0.38 to >-1.14 11/25 90.2 36.8 41.0

6 <-1.14 13/23 100.0 42.9 51.7

NIEC, N Engl J Med 1988;319:983-9

Agreement of endoscopic findings

Gastroenterology 1990;98:156-162

Endoscopic features

Frequency (%)

Agreement (%) Kappa indexb

Overall Single class p valueª Overall Single class

Esophageal varices

Size 82±18 0.59

0 19 79±18 0.59

1 36 75±20 <0.01 0.45

2 38 86±16 [1-3] 0.60

3 7 100±0 0.84

Extent 75±19 0.37

1/3 24 66±22 0.28

2/3 67 78±17 <0.05 0.30

3/3 9 82±24 0.58

color 77±19 0.28

white 28 78±18 NS

Blue 72 75±18

Red sign 88±17 0.58

Yes 32c 86±19 NS

No 68 89±17

Variceal Pressure Variceal Wall

Transmural P = (Variceal P – Luminal P)

Variceal Wall Tension = Transmural Pressure x Radius

Variceal Wall Thickness

Factors related to bleeding of esophageal varices

R

Luminal Pressure

High HVPG Transmural pressure

Variceal size Radius of the varix

Red color signs Wall thickness

Valuable findings to be noted

Size of varix and RC sign are most important risk factors

• To assess the risk of bleeding-NIEC index

Size of varices Points to add

Small 8.7

Medium 13.0

Large 17.4

Red wale markings

Absent 3.2

Mild 6.4

Moderate 9.6

Severe 12.8

Child-Pugh class

A 6.5

B 13.0

C 19.5

NIEC index Rate of Bleeding (%)

6 months 12 months

<20 0 1.6

~25 5.4 11.0

~30 8.0 14.8

~35 13.1 23.3

~40 21.8 37.8

>40 58.5 68.9

N Engl J Med 1988;319:983-9

This multicenter Italian prospective study showed the Beppu score significantly overestimated the probability of first esophageal varix hemorrhage.

How to measure the varix size?

1. Naked-eye

2. Specific size marker

3. Computed tomography

4. Balloon assisted endoscopic ultrasound

5. Endoscopic ultrasound with mini-probe

The issue for measuring the varix size

F1: small-caliber varices, not disappear with insufflation.

F2: Moderately enlarged, beady varices, less than 1/3 of the

esophageal lumen

F3: Markedly enlarged, nodular or tumor-shaped varices,

more than 1/3 of the esophageal lumen

World J. Surg 1995;19:420-423

On EGD, esophageal varices should be graded as small or large (>5 mm) with the latter classification encompassing medium-sized varices when 3 grades are used (small, medium, large). (Class IIa, Level C).

AASLD practice guideline Hepatology 2007;46:922-938

How to measure the varix size

GASTROENTEROLOGY 1997;113:1640–1646

Esophageal varices were graded from 1 to 4

grade 1 : ≤3 mm in diameter;

grade 2 : 4-6 mm,

grade 3, 7-10 mm,

grade 4, ≥11 mm

Gastrointest Endosc 2005;61:58-66 Baveno III consensus workshop J Hepatology 1992;15:256-261

Varix size: Sum of Esophageal Variceal Cross-Sectional Surface Area?

• Risk of Esophageal Variceal Bleeding Based on Endoscopic Ultrasound evaluation of the Sum of Esophageal Variceal CSA

Am J Gastroenterol 2003;98:454–459.

The grade of the esophageal varices by endoscopy was not a significant predictor of future variceal bleeding in this study.

Using a cutoff value for the CSA of 0.45 cm2, the sensitivity and specificity for future variceal bleeding above and below this point is 83% and 75%.

The objectiveness of EUS measurement

Gastrointest Endosc 1996;44:425-8

The intraobserver and interobserver correlations reflecting the objectiveness of the EUS measurement were excellent.

Intraobserver correlations

Interobserver correlations

Variceal radius 0.98 0.97

Wall thickness 0.92 0.91

Variceal radius was not correlated with wall thickness (r=-0.08)

Measurement of varix size with endoscopic ultrasound

• Measure the radius of varix by 20MHz IVUS

• Grade I~V

• Interobserver correlation r=0.88

0% 30% 60% 100%

Miller LS et al. HEPATOLOGY 1996;24:552-555

6.5mm

Endoscopic ultrasound for the management of esophageal varices

Peri-, Para-EV & Perforating vein

Muscular layer

Muscularis externa

Lumen

Mucosa & Submucosal

layer

Peri-esophageal collateral veins (peri-ECVs)

Para-esophageal collateral veins (para-ECVs)

Perforating vein (connected with para-ECVs) Perforating vein

(connected with peri-ECVs)

Modified from El-Saadany, M. et al. Endoscopy 2008;40:690-696

Large Paraesophageal collateral vein and perforating vein are

considered as an important risk factor for variceal recurrence

Gastrointest Endosc 2001;53:77-84

How to deal with it?

1. Nonselective β-blocker (NSBB)

2. Endoscopic injection sclerotherapy (EIS)

3. Endoscopic variceal ligation (EVL)

4. Combination of EIS+EVL

5. Combination of NSBB + EVL

Nonselective β-blocker for the primary prevention of bleeding

• Medium/large varices & Not bled

– High risk of hemorrhage (Child B/C or red wale markings)

• Nonselective ß-blockers or EVL may be recommended (IA).

– No high risk of hemorrhage

• Nonselective ß-blockers are preferred

• EVL: CIx, intolerance or non-compliance to ß-blockers (IA)

2005 ASGE guideline, Gastrointest Endosc 2005;62:651-655 2007 AASLD and ACG Practise guideline

• Small varices & Not bled

– High risk of hemorrhage (Child B/C or red wale markings),

• Nonselective ß-blockers should be used for (IIA)

– No increased risk of hemorrhage

• Nonselective ß-blockers can be used.

The use of beta-blockers is associated with poor survival in patients with refractory ascites.

HEPATOLOGY 2010;52:1017-1022

patients not taking b-blocker

patients taking b-blocker

Median survival

20.2 months (4.8-35.2)

5.0 months (3.5-6.5)

Beta-blockers in patients with end-stage cirrhosis needs to be cautioned.

The use of beta-blockers may be associated with a high risk of paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites.

J Hepatol 2011;55:794-9

Pro

babili

ty o

f bein

g fre

e o

f AKI

The effect of long-term use of non-selective beta-blocker on the development of acute kidney

injury in patients with liver cirrhosis

208 patients developed AKI from 2,250 liver transplantation waitlist registrants.

Median follow-up duration : 20.3 (range:3~201) months.

Kim SG et al. 2014 KASL

1.00

0.19

1.53

4.27

Ascites(-) &

NSBB(-)

Ascites(-) &

NSBB(+)

Ascites(+) &

NSBB(-)

Ascites(+) &

NSBB(+)

Haza

rd ratio o

f AKI

Endoscopic injection sclerotherapy (EIS)

Injection of 5% ethanolamine oleate in the varix

Randomized trials showed that EVL is more effective than EIS in controlling esophageal variceal bleeding.

1. makes less complications 2. requires fewer treatment sessions to achieve eradication 3. improves the survival of patients

Endoscopic injection sclerotherapy (EIS) vs. Endoscopic variceal ligation (EVL)

Authors Treatment N Complications, %

Eradication,%

Recurrence,%

Rebleed,%

Stiegmann et al. EIS 65 22 56 50 48 EVL 64 2 55 33 36 Gimson et al. EIS 49 57 71 - 53 EVL 54 67 82 - 30 Laine et al. EIS 39 56 69 - 44 EVL 38 24 59 - 26 Lo et al. EIS 59 19 63 - 51 EVL 61 3 74 - 33 Hou et al. EIS 67 22 79 30 33 EVL 67 5 87 48 18 Lo et al EIS 34 29 - - 33 EVL 37 5 - - 17 Baroncini et al. EIS 54 31 92 13 19 EVL 57 11 93 30 16 Avgerinos et al. EIS 40 60 97 - 47 EVL 37 35 93 - 27 Sarin et al. EIS 48 10 92 8 21 EVL 47 0 96 29 6 Hou et al. EIS 84 - 86 - 38 EVL 84 - 88 - 24

Ann Intern Med 1995;123:280-287

Combination treatment (EIS + EVL) vs. Endoscopic variceal ligation (EVL) alone

Dig Dis Sci 2005;50:399-406

A meta-analysis showed that there is no additive effect of combination treatment. Combination EVL and sclerotherapy had more esophageal stricture formation than EVL alone.

Variceal rebleeding Mortality

Endoscopic variceal ligation (EVL); Multi-band ligation

Six-shooter Saeed multi-band ligator® (Wilson-Cook)

Speedband® Superview super7 (Microvasive)

FDA-MAUDE(manufacturer and user facility device experience)

Visual Field

Endoscopic variceal ligation

EVL for Active EV Bleeding

Sohendra N, et al. Therapeutic Endoscopy

EVL for Active EV Bleeding

Advantage of EVL

• Easier to learn and require less experience

• Complications are less operator-dependent

• Fewer complications

• Eradicating varices more rapidly with less recurrent

bleeding

• improve survival (compared to EIS)

• EVL is the recommended for acute esophageal variceal

bleeding, primary prophylaxix and prevention of

variceal rebleeding (1b;A)

2010 Baveno V Revising consensus

Complications of EVL

• 2-20% of patients treated by EVL

• Chest pain and dysphagia < 20%

• Mediastinitis, perforation, esophageal stricture

: extremely rare

• Shallow ulcer, only a minority associated with bleeding.

• 11/150 patients (7.3%) had post-EVL ulcer bleeding

Clin Gastroenterol Hepatol 2009;7:988-93

Follow-up after EVL

Manangement of post-EVL ulcer

Pantoprazole reduces the size of postbanding ulcers

after variceal band ligation: a randomized, controlled Trial Method: day 1 : IV pantoprazole 40mg,

day 2-10 : PO pantoprazole 40mg

HEPATOLOGY 2005;41:588-594

Control (n=20)

Pantoprazole (n=22)

P-value

No. of ulcers, day 10, mean (SE)

2.25 (0.31) 2.18 (0.20) 0.85

Ulder size (mm2), day 10, mean (SE)

82 (22) 37 (9) 0.01

Dysphagia present, day 10, n (%)

1 (5) 3 (14) 0.61

Chest pain present, day 10, n (%)

0 (0) 1 (5) 1.0

Change of gastric varices after EVL

Obliteration of gastric varices

Hemodynamics of varices and collateral vessels

Non-dominant

Lt.gastric vein

short.gastric vein

Paraesophageal collateral vein

Perforating vein

Ant. branch

Post. branch

Dominance was defined as lack of one branch, or a ratio of the smaller branch diameter to the larger branch diameter of less than 0.75

Hemodynamics of varices and collateral vessels

High risk of Esophageal varix recurrence

Gastric varix can develop after esophageal band ligation.

Anterior dominant

Hemodynamics of varices and collateral vessels

Posterior dominant

Gastriorenal shunt Low risk of Esophageal varix recurrence

Gastric varix can disappear after esophageal band ligation.

Recurrence of esophageal varices after EVL

J Gastroenterol 2007; 42:219–224

Anterior dominant : high risk of recurrence of esophageal varices

Color-Doppler EUS

Endoscopic Secondary Prophylaxis

• Ix : survivor from episode of active variceal hemorrhage. (I, A)

• Best option: “ß-blockers plus EVL” (I, A).

• Maximal tolerated dose of nonselective ß-blocker

• Repeat EVL every 1-2 weeks (?) until obliteration.

• EGD after obliteration.

– 1-3 months ⇒ then every 6-12 months (I, C).

2005 ASGE guideline, Gastrointest Endosc 2005;62:651-655 2007 AASLD and ACG Practise guideline

Bi-weekly vs. Bi-monthly EVL session

Am J Gastroenterol 2005;100:2005–2009

Additional treatment for recurrent varices after complete eradication

Recurrence rate after complete eradication

A Randomized Control Trial of Bi-monthly Versus Bi-weekly Endoscopic Variceal Ligation of Esophageal Varices.

The second treatment session after recanalization of variceal blood flow had a greater impact on the stimulation of shunt formation

Summary

• Esophageal varix size and red color sign are the most

important findings to predict variceal bleeding.

• EVL is effective for control of active bleeding, primary

and secondary prophylaxis in patients with EV.

• Endoscopic ultrasound is useful to assess the size of

esophageal varices and predict variceal bleeding

Conclusions

• Endoscopic variceal ligation is the most effective

method to control active bleeding and prophylaxis of

gastro-esophageal varices.

• To provide successful endoscopic treatment, you

should know about complication of EVL and anatomy

of varices.

Thank you for

your attention

Greatly appreciation to Dr. Kim Young Seok, Dr. Jang Jae

Young, Kim Yulhee for giving an advice and materials.