1. I A S G - ROMANIAN C HAPTER
BUC HARES T 1 1 s t April 2 0 0 3
ENDOSCOPIC THERAPYIN THE MANAGEMENTOF
VARICEAL HEMORRHAGE
Cristian Gheorghe
Center of Gastroenterology & Hepatology
Fundeni Clinical Institute
Bucharest Romania

2. BACKGROUND
s Variceal bleeding is a common and
serious complication of portal
hypertension (PHT)
s The optimal management of patients
with variceal bleeding today requires
a multidisciplinary approach by a
team that includes
gastroenterologist-endoscopist,
interventional radiologist, and
surgeon.

3. SURVIVAL CURVES AFTER ACUTE VARICEAL BLEEDING
Comparison during the last 6 decades
100
90
80 Raztnoff
70 (1941)
Nachalas
60 (1955)
Graham
50
(1981)
40 Pinto
(1989)
30 Current
20 (2001)
10
0
0 2 6 12 18 24 36
mo. mo. mo. mo. mo. mo. mo.

4. MODALITIES OF ENDOSCOPIC TREATMENTFOR VARICEAL
BLEEDING
s Endoscopic sclerotherapy (EST)
« Crafoord & Frenckner first introduced EST 1939
« rediscovered late ~‘70
« first choice for acute variceal bleeding control over the two past decades
(‘80-’90)
s Endoscopic variceal ligation
« Stiegmann 1986
« Saeed 1995 “sixshooter” band ligator
C ha la s a ni N, e t a l Am J Ga s tro e nte ro l 2 0 0 3

5. ENDOSCOPIC SCLEROTHERAPY
s successful in controling active
bleeding in 90%
s useful in reduction of frequency and
severity of recurrent variceal
bleeding (secondary prophylaxis)
s not indicated for the primary
prevention
Paq ue t KJ, He p ato lo gy 1 9 8 5
Ro b e rts LR, M ayo C lin Pro c 1 9 9 6
AS GE Guid e line s , Gas tro inte s t End o s c 2 0 0 2

6. ENDOSCOPIC SCLEROTHERAPY
s ESTmay be performed by injecting
the sclerosant
« directly into the varix(intravariceal)
to produce thrombosis
« adjacent to the varix(paravariceal)
to induce submucosal fibrosisand
obliteration of deeper perforating
vessels
« combining the two techniques during
the same session

7. ENDOSCOPIC SCLEROTHERAPY
s Injection of the sclerosant agent
intravariceal produces thrombosis
and paravariceal determines
submucosal fibrosis and obliteration
of deeper perforating vessels
s In practice, the combination of both
techniques may be used during the
same session

8. ENDOSCOPIC SCLEROTHERAPY
Ag e nt Conc e ntra tion Ulc e rs (%) Oblite ra tion
(%) (%)
Alc ohol 95 80 60
S odium 1 .0 -3 % 40 90
te tra de c yl
s ulfa te
S odium 5% 30 80
m orua te
P olidoc a nol 0 .5 % 51 82
E tha nola m ine 5% 7% 33%
ole a te
Ad ap te d fro m Je ns e n DM, End o s c o p y 1 9 8 6

9. ENDOSCOPIC SCLEROTHERAPY
q
Gastric varices
ª esogastric varices type I (GOV 1)
ª esogastric varices type II (GOV 2)
ª isolate gastric varices type I (IGV 1)
ª isolate gastric varices type I (IGV 2)
q Esogastric varices type I and II may be
treated with ESTbelowthe esogastric
junction
S arin S K, In: De Franc his R. Po rtal Hyp e rte ns io n (Bave no III),
2001
AS GE Guid e line s 2 0 0 2

10. ENDOSCOPIC CYANOACRYLATE INJECTION
s Histoacryl is a watery substance that polymerises and hardens within
seconds of its contact with blood; it permanently ocludes the vessel
lumen
s The technique of injection is that of intravariceal sclerotherapy
s Risks and drawbacks: embolization and damage of the endoscope
s Useful particularly for gastric varices type IGV

11. « 130 patients underwent sclerotherapy with alcohol - for acute
variceal bleeding
« follow up period - 4 years
La rge oe s opha ge a l va ric e s 80 %
Va ric e a l ble e ding his tory 7 6 .9 %
He m ora gic e me rge nc ie s 23 %
Im m edia te m orta lity 0 .7 6 %
21%
36%
64%
79%
R - b le e ding
e C nse cutive m o rb idity
o
Yes No Y es No
G h e o rg h e C ., G h e o rg h e L. - 1 s t UEG W , A th e n s ; He lle n ic J
G a s tro e n te ro l (S u p p l) 1 9 9 2

12. ENDOSCOPIC VARICEAL LIGATION (EVL)
s indicated for controling active
bleeding
s useful in reduction of frequency
and severity of recurrent variceal
bleeding (secondary prophylaxis)
s indicated for the primary
prevention

13. ENDOSCOPIC VARICEAL LIGATION (EVL)
s A transparent cylinder is
attached to the end of the
forward viewing endoscope
s Prestressed rubber bands are
already positioned at the distal
end of the cylinder
s A drawstring that extends from
the cylinder is backloaded
through the working channel and
connected to the handle
mechanism positioned at the
proximal part of the channel

14. ENDOSCOPIC VARICEAL LIGATION (EVL)
s EVL is begun at the most distal point
of the variceal column
s Having targeting the varix, the tip of
the endoscope is angulated toward
the varixand suction is applied
continuously until the varixis
sucked completely into the cylinder
s The band is release over the
entrapped varixby pulling the trip
wire

15. « 132 patients with acute variceal bleeding were treated with EVL
until variceal eradication
« mean followup period - 12 months
I pe nde nt pre dicto rs o f re b le e ding
nde
OR Pvalue
P G (+)
Ho 5.63 0.003
E (+)
H 9.98 0.005
32%
68%
Yes No
R -b le e ding
e
Ghe o rghe C - Gut 2 0 0 2 ; 5 1 S up p l 3 , A1 8 4

16. RANDOMIZED COMPARATIVE TRIALS OF EST& EVL
Am e ta-ana lysis o f pub lishe d a rticle s 1 9 9 2 - 2 0 0 1
RATE OF ERADICATION
88
Masci (1999) 82
Hou (1999) 88
86
Sarin (1997) 96
92
Avgerinos (1997) 93
97
Baroncini (1997) 93
92
Hou (1995) 87
EVL
79
Lo (1995) 74 EST
63
Laine (1993) 59
69
82
Gimson (1993)
71
55
Stiegmann (1992) 56
0 20 40 60 80 100

17. Sample Chi2 P value Effect size
size (r)
S tie g m a n n 129 1.13 0.28 0.09
(1 9 9 2 )
G im s o n (1 9 9 3 ) 103 1.45 0.22 0.11
La in e (1 9 9 3 ) 77 1.06 0.30 0.11
Lo (1 9 9 5 ) 120 1.69 0.19 0.11
Ho u (1 9 9 5 ) 134 1.31 0.25 0.09
Ho u (1 9 9 9 ) 168 0.20 0.64 0.03
B a ro n c in i 111 0.18 0.66 0.04
(1 9 9 7 )
A v g e rin o s 77 1.22 0.26 0.12
(1 9 9 7 )
S a rin (1 9 9 7 ) 95 0.66 0.41 0.08
M a s c i (1 9 9 9 ) 100 0.7 0.4 0.08

18. RATE OF VARICEAL ERADICATION AFTER EST/ EVL
To tal N = 1105 N b e r o f S
um tudie s: k = 1 0
• Po pula tio n e ffe ct size
90 78 82.5
r = 0 .0 3
80 • 9 5 % co nfide nce inte rva l o f po p. e ffe ct
size : fro m
70
60 0 .0 1 3 to 0 .0 6 3
• E ine d va ria nce
xpla
50
r-sq ua re = 0 .0 0 1
40 • C rre spo nding Z N rm al
o in o
30 22 17.5
D istrib utio n = 1 .2 7
20 •S ignifica nce
10 p = 0 .1 - NS
0 • Fail S fe Nfo r critical r o f .0 5 = 2
a
EST EVL • Fail S fe Nfo r critical r o f .1 0 = 6
a
Eradication ( +) Eradication ( - )
Pe rce nta ge o f o b se rve d va riance a cco unte d fo r b y sam pling e rro r
= 1 0 0 .0 0 % → ho m o ge ne o us
Te st o f ho m o ge ne ity C hi-sq ua re = 1 .9 8 → ho m o ge ne o us
Significa nce p = 0 .9 9 1 7

19. RANDOMIZED COMPARATIVE TRIALS OF EST& EVL
Am e ta-ana lysis o f pub lishe d a rticle s 1 9 9 2 - 2 0 0 1
RATE OF COMPLICATION
18
* Masci (1999) 38
0
* Sarin (1997) 10
35
* Avgerinos (1997) 60
11
* Baroncini (1997) 31
Lo (1997) 5
* 29
5
EVL
* Hou (1995) 22
* Lo (1995) 3
EST
19
* Laine (1993) 24
56
56
Gimson (1993)
57
* 2
Stiegmann (1992) 22
0 20 40 60 80
* p < 0.05

20. Sample Chi2 P value Effect size
size (r)
S tie g m a n n 129 10.06 0.001 0.269
(1 9 9 2 )
G im s o n (1 9 9 3 ) 103 0.99 0.31 0.09
La in e (1 9 9 3 ) 77 8.57 0.03 0.31
Lo (1 9 9 5 ) 120 7.3 0.006 0.239
Ho u (1 9 9 5 ) 134 9.2 0.002 0.253
Lo (1 9 9 7 ) 71 7.2 0.007 0.3
B a ro n c in i 111 7.4 0.006 0.25
(1 9 9 7 )
A v g e rin o s 77 4.7 0.02 0.2398
(1 9 9 7 )
S a rin (1 9 9 7 ) 95 5.16 0.02 0.227
M a s c i (1 9 9 9 ) 100 4.9 0.025 0.216

21. RATE OF VARICEAL COMPLICATION AFTER EST& EVL
To tal N = 1017 N b e r o f S
um tudie s: k = 1 0
85.8 • Po pulatio n e ffe ct size
90
r = 0 .2 1 1 3 2
80 68 • 9 5 % co nfide nce inte rva l o f po p.
70 e ffe ct size : fro m
60 0 .1 7 to 0 .2 5
50 • E ine d va riance
xpla
40 32 r-sq uare = 0 .0 4 4 6 5
• C rre spo nding Z N rm a l
o in o
30
14.2 D istrib utio n = 6 .8 0 7 7 3
20 • Significa nce
10 p→ 0
0 • Fa il Safe Nfo r critica l r o f .0 5 =
EST EVL 32
• Fa il Safe Nfo r critica l r o f .1 0 =
Complications ( + ) Complications ( - ) 11
Pe rce nta ge o f o b se rve d va ria nce acco unte d fo r b y sam pling e rro r
= 1 0 0 .0 0 % → ho m o ge ne o us
Te st o f ho m o ge ne ity C hi-sq ua re = 4 .3 6 2 7 6 → ho m o ge ne o us
Significa nce p = 0 .8 8 5 9 5 8

22. RANDOMIZED COMPARATIVE TRIALS OF EST& EVL
Am e ta-ana lysis o f pub lishe d article s 1 9 9 2 - 2 0 0 1
RECURRENCE OF VARICES
32
Masci (1999)
27
* Sarin (1997) 29
8
30
* Baroncini (1997) 13 EVL
48 EST
* Hou (1995)
30 * p < 0.05
33
Stiegmann (1992)
50
0 10 20 30 40 50 60

23. Sample Chi2 P value Effect size
size (r)
S tie g m a n n 129 3.59 0.058 0.16
(1 9 9 2 )
Ho u (1 9 9 5 ) 134 4.5 0.03 0.18
B a ro n c in i 111 4.65 0.03 0.20
(1 9 9 7 )
S a rin (1 9 9 7 ) 95 6.03 0.01 0.25
M a s c i (1 9 9 9 ) 100 0.43 0.5 0.06
0.98 1.99 4.32
Stiegmann 0.21 0.47
0.98
Hou
Sarin 0.05 0.24 0.87
Masci 0.29 0.75 1.94
0.12 0.35 0.83
Baroncini
0.47 0.69 0.92
META
OR 0 1 2

24. RATE OF VARICEAL RECURRENCE AFTER EST& EVL
To tal N = 569 N b e r o f S
um tudie s: k = 5
• Po pulatio n e ffe ct size
80 73.3 r = 0 .1 4 3
65.3 • 9 5 % co nfide nce inte rva l o f po p.
70
e ffe ct size : fro m
60 0 .0 7 4 to 0 .2 1
50 • E ine d va riance
xpla
34.7
40 26.7 r-sq uare = 0 .0 2
30 • C rre spo nding Z N rm a l
o in o
D istrib utio n = 3 .4 3
20
• Significa nce
10 p = 0 .0 0 0 2 9
0 • Fa il Safe Nfo r critica l r o f .0 5 = 9
EST EVL
• Fa il Safe Nfo r critica l r o f .1 0 = 2
Varices recurrence ( + ) Varices recurrence ( - )
Pe rce ntage o f o b se rve d va ria nce a cco unte d fo r b y sam pling e rro r
= 1 0 0 .0 0 % → ho m o ge ne o us
Te st o f ho m o ge ne ity C hi-sq ua re = 3 .2 4 → ho m o ge ne o us
Significa nce p = 0 .5 1

25. RANDOMIZED COMPARATIVE TRIALS OF EST& EVL
Am e ta-ana lysis o f pub lishe d article s 1 9 9 2 - 2 0 0 1
RATE OF REBLEEDING
Masci (1999) 14
8
24
Hou (1999) 38
*
6
* Sarin (1997) 21
Avgerinos (1997) 27
47
Baroncini (1997) 16
19
Lo (1997) 17
33 EVL
* Hou (1995) 18
33 EST
* Lo (1995) 33
51
Laine (1993) 26
44
30
* Gimson (1993) 53
36
Stiegmann (1992) 48
0 10 20 30 40 50 60
* p < 0.05

26. Sample Chi2 P value Effect size
size (r)
S tie g m a n n (1 9 9 2 ) 129 1.83 0.17 0.11
G im s o n (1 9 9 3 ) 103 5.84 0.01 0.23
La in e (1 9 9 3 ) 77 2.52 0.11 0.18
Lo (1 9 9 5 ) 120 4.02 0.044 0.18
Ho u (1 9 9 5 ) 134 3.94 0.047 0.17
Lo (1 9 9 7 ) 71 2.5 0.11 0.18
B a ro n c in i (1 9 9 7 ) 111 0.14 0.7 0.03
A v g e rin o s (1 9 9 7 ) 77 3.43 0.063 0.21
S a rin (1 9 9 7 ) 95 4.19 0.04 0.21
Ho u (1 9 9 9 ) 168 4.01 0.045 0.15
M a s c i (1 9 9 9 ) 100 0.91 0.33 0.09

27. 0.76 1.63 3.5
S gm a nn
tie
1.1 2.58 6.65
G so n
im
0.75 2.16 6.34
Laine
1.02 2.12 4.76
L (1 9 9 5 )
o
1.05 2.24 5.43
H u (1 9 9 5 )
o 0.41 1.21 3.63
B ncini
aro 0.85 2.44 7.12
A rino s
vge 0.89 3.86
23.09
Sarin 1.08 1.97 4.06
H u (1 9 9 9 )
o
0.11 0.53 2.29
Masci
0.70 2.47 8.93
L (1 9 9 7 )
o
1.53 1.59 2.07
META
OR 0 1 2 3 7

28. RATE OF REBLEEDING AFTER EST& EVL
To tal N = 1185 N b e r o f S
um tudie s: k = 1 1
80 75.9 • Po pulatio n e ffe ct size
66
70 r = 0 .1 2
• 9 5 % co nfide nce inte rva l o f po p.
60 e ffe ct size : fro m
50 0 .0 8 to 0 .1 6
34
40 • E ine d va riance
xpla
24.1
30 r-sq uare = 0 .0 1
20 • C rre spo nding Z N rm a l
o in o
10 D istrib utio n = 4 .3 2
• Significa nce
0
EST EVL p = 0 .0 0 0 0 1
• Fa il Safe Nfo r critica l r o f .0 5 =
Varices re-bleeding ( + ) Varices re-bleeding ( - ) 16
Pe rce nta ge o f o b se rve d va ria nce acco unte d fo r b y sam pling e rro r • Fa il Safe Nfo r critica l r o f .1 0 = 2
= 1 0 0 .0 0 % → ho m o ge ne o us
Te st o f ho m o ge ne ity C hi-sq ua re = 6 .2 5 → ho m o ge ne o us
Significa nce p = 0 .7 9

29. PROPOSED ALGORITHM FOR THE Variceal bleeding
MANAGEMENTOF VARICEAL
BLEEDING Endoscopy available ?
YES NO
UGI Endoscopy Glypressin
Somatostatin
Octreotide
Oesophageal variceal Gastric variceal
bleed bleed
Band ligation / Gastroesophageal Isolated gastric
Sclerotherapy varices varices
Uncontrolled Controlled Treat as oesophageal TIPPS /
varices Butylcyanoacrylate
Baloon tamponade Banding eradication
programme
UK Guid e line s , Gut 2 0 0 0
TIPS / surgery