document29
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ENDOSCOPIC THERAPY IN THE MANAGEMENT OF VARICEAL HEMORRHAGE
I A S G - ROMANIAN CHAPTER
BUCHARES T 1 1 s t April 2 0 0 3
Cristian GheorgheCenter of Gastroenterology & Hepatology
Fundeni Clinical InstituteBucharest Romania
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BACKGROUND
■ Variceal bleeding is a common and serious complication of portal hypertension (PHT)
■ The optimal management of patients with variceal bleeding today requires a multidisciplinary approach by a team that includes gastroenterologist-endoscopist, interventional radiologist, and surgeon.
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SURVIVAL CURVES AFTER ACUTE VARICEAL BLEEDING Comparison during the last 6 decades
0
10
20
30
40
50
60
70
80
90
100
0mo.
2mo.
6mo.
12mo.
18mo.
24mo.
36mo.
Raztnoff(1941)Nachalas(1955)Graham(1981)Pinto(1989)Current(2001)
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MODALITIES OF ENDOSCOPIC TREATMENT FOR VARICEAL BLEEDING
Chalas ani N, e t al Am J Gas tro e nte ro l 2 0 0 3
■ 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)
■ Endoscopic variceal ligation ➠ Stiegmann 1986➠ Saeed 1995 “six shooter” band ligator
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ENDOSCOPIC SCLEROTHERAPY
■ successful in controling active bleeding in 90%
■ useful in reduction of frequency and severity of recurrent variceal bleeding (secondary prophylaxis)
■ not indicated for the primary prevention
Paq ue t KJ, He pato lo gy 1 9 8 5Ro be rts LR, Mayo C lin Pro c 1 9 9 6
AS GE Guid e line s , Gas tro inte s t Endo s c 2 0 0 2
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ENDOSCOPIC SCLEROTHERAPY
■ EST may 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
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ENDOSCOPIC SCLEROTHERAPY
■ Injection of the sclerosant agent intravariceal produces thrombosis and paravariceal determines submucosal fibrosis and obliteration of deeper perforating vessels
■ In practice, the combination of both techniques may be used during the same session
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ENDOSCOPIC SCLEROTHERAPY
Age nt Conc e ntra tion(%)
Ulc e rs (%) Oblite ra tion(%)
Alc ohol 9 5 8 0 6 0S odiumte tra de c yls ulfa te
1 .0 -3 % 4 0 9 0
S odiumm orua te
5 % 3 0 8 0
P olidoc a nol 0 .5 % 5 1 8 2
E tha nola m ineole a te
5 % 7 % 3 3 %
Adapte d fro m Je ns e n DM, Endo s c o py 1 9 8 6
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● Gastric varices➟ esogastric varices type I (GOV 1)➟ esogastric varices type II (GOV 2)➟ isolate gastric varices type I (IGV 1)➟ isolate gastric varices type I (IGV 2)
● Esogastric varices type I and II may be treated with EST below the esogastric junction
S arin S K, In: De Franc his R. Po rtal Hype rte ns io n (Bave no III), 2 0 0 1
AS GE Guid e line s 2 0 0 2
ENDOSCOPIC SCLEROTHERAPY
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ENDOSCOPIC CYANOACRYLATE INJECTION
■ Histoacryl is a watery substance that polymerises and hardens within seconds of its contact with blood; it permanently ocludes the vessel lumen
■ The technique of injection is that of intravariceal sclerotherapy■ Risks and drawbacks: embolization and damage of the endoscope■ Useful particularly for gastric varices type IGV
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La rge oe s opha ge a l va ric e s 8 0 %
Va ric e a l ble e ding his tory 7 6 .9 %
He m ora gic e me rge nc ie s 2 3 %
Im m edia te m orta lity 0 .7 6 %
➠ 130 patients underwent sclerotherapy with alcohol - for acute variceal bleeding➠ follow up period - 4 years
21%
79%
Yes No
36%
64%
Yes NoGh e o rg h e C ., Gh e o rg h e L. - 1 s t UEGW , A th e n s ; He lle n ic J
Ga s tro e n te ro l (S u p p l) 1 9 9 2
Re - b le e ding Co nse c utive m o rb idity
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ENDOSCOPIC VARICEAL LIGATION (EVL)
■ indicated for controling active bleeding
■ useful in reduction of frequency and severity of recurrent variceal bleeding (secondary prophylaxis)
■ indicated for the primary prevention
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ENDOSCOPIC VARICEAL LIGATION (EVL)
■ A transparent cylinder is attached to the end of the forward viewing endoscope
■ Prestressed rubber bands are already positioned at the distal end of the cylinder
■ 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
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ENDOSCOPIC VARICEAL LIGATION (EVL)
■ EVL is begun at the most distal point of the variceal column
■ Having targeting the varix, the tip of the endoscope is angulated toward the varix and suction is applied continuously until the varix is sucked completely into the cylinder
■ The band is release over the entrapped varix by pulling the trip wire
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32%
68%
Yes No
➠ 132 patients with acute variceal bleeding were treated with EVL until variceal eradication➠ mean follow up period - 12 months
Re -b le e d ing
Ghe o rghe C - Gut 2 0 0 2 ; 5 1 S uppl 3 , A1 8 4
OR P value
PHGo (+) 5.63 0.003
EH (+) 9.98 0.005
Inde pe nde nt pre dic to rs o f re b le e ding
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RANDOMIZED COMPARATIVE TRIALS OF EST & EVLA m e ta -a na lysis o f pub lishe d a rtic le s 1 9 9 2 - 2 0 0 1
RATE OF ERADICATION
5655 71
826959
63 7479
8792
939793
92 9686
8882
88
0 20 40 60 80 100
Stiegmann (1992)
Gimson (1993)
Laine (1993)
Lo (1995)
Hou (1995)
Baroncini (1997)
Avgerinos (1997)
Sarin (1997)
Hou (1999)
Masci (1999)
EVLEST
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Sample Sample sizesize
ChiChi22 P valueP value Effect size Effect size (r)(r)
S tie g m a n n (1 9 9 2 )
129 1.13 0.28 0.09
Gim 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 0.11Lo (1 9 9 5 ) 120 1.69 0.19 0.11Ho u (1 9 9 5 ) 134 1.31 0.25 0.09Ho u (1 9 9 9 ) 168 0.20 0.64 0.03B a ro n c in i (1 9 9 7 )
111 0.18 0.66 0.04
A vg e rin o s (1 9 9 7 )
77 1.22 0.26 0.12
S a rin (1 9 9 7 ) 95 0.66 0.41 0.08M a s c i (1 9 9 9 ) 100 0.7 0.4 0.08
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RATE OF VARICEAL ERADICATION AFTER EST / EVLRATE OF VARICEAL ERADICATION AFTER EST / EVL
78
22
82.5
17.5
0102030405060708090
EST EVL
Eradication ( +) Eradication ( - )
To ta l N = 1105 Num b e r o f Studie s: k = 1 0• Po pula tio n e ffe c t s ize r = 0 .0 3• 9 5 % c o nfide nc e inte rva l o f po p. e ffe c t s ize : fro m
0 .0 1 3 to 0 .0 6 3• Expla ine d va ria nc e r-sq ua re = 0 .0 0 1• Co rre spo nding Z in No rm a l Distrib utio n = 1 .2 7• Signific a nc e p = 0 .1 - NS• Fa il Sa fe N fo r c ritic a l r o f .0 5 = 2• Fa il Sa fe N fo r c ritic a l r o f .1 0 = 6
Pe rc e nta g e o f o b s e rve d va ria nc e a c c o unte d fo r b y s a m pling e rro r = 1 0 0 .0 0 % → ho m o g e ne o us Te st o f ho m o g e ne ity Chi-sq ua re = 1 .9 8 → ho m o g e ne o us Sig nific a nc e p = 0 .9 9 1 7
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222 57
565624
19322
529
53111
603510
038
18
0 20 40 60 80
Stiegmann (1992)
Gimson (1993)
Laine (1993)
Lo (1995)
Hou (1995)
Lo (1997)
Baroncini (1997)
Avgerinos (1997)
Sarin (1997)
Masci (1999)
EVLEST
*
***
*
**
*
*
* p < 0.05
RANDOMIZED COMPARATIVE TRIALS OF EST & EVLA m e ta -a na lysis o f pub lishe d a rtic le s 1 9 9 2 - 2 0 0 1
RATE OF COMPLICATION
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Effect size Effect size (r)(r)
P valueP valueChiChi22Sample Sample sizesize
0.2160.0254.9100M a s c i (1 9 9 9 )
0.2270.025.1695S a rin (1 9 9 7 )
0.23980.024.777A vg e rin o s (1 9 9 7 )
0.250.0067.4111B a ro n c in i (1 9 9 7 )
0.30.0077.271Lo (1 9 9 7 )
0.2530.0029.2134Ho u (1 9 9 5 )
0.2390.0067.3120Lo (1 9 9 5 )
0.310.038.5777La in e (1 9 9 3 )
0.090.310.99103Gim s o n (1 9 9 3 )
0.2690.00110.06129S tie g m a n n (1 9 9 2 )
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RATE OF VARICEAL COMPLICATION AFTER EST & EVLRATE OF VARICEAL COMPLICATION AFTER EST & EVL
32
68
14.2
85.8
0102030405060708090
EST EVL
Complications ( + ) Complications ( - )
To ta l N = 1017 Num b e r o f Studie s: k = 1 0• Po pula tio n e ffe c t s ize r = 0 .2 1 1 3 2• 9 5 % c o nfide nc e inte rva l o f po p. e ffe c t s ize : fro m
0 .1 7 to 0 .2 5• Expla ine d va ria nc e r-sq ua re = 0 .0 4 4 6 5• Co rre spo nd ing Z in No rm a l Distrib utio n = 6 .8 0 7 7 3• Signific a nc e p → 0• Fa il Sa fe N fo r c ritic a l r o f .0 5 =
3 2• Fa il Sa fe N fo r c ritic a l r o f .1 0 =
1 1Pe rc e nta g e o f o b s e rve d va ria nc e a c c o unte d fo r b y s a m pling e rro r = 1 0 0 .0 0 % → ho m o g e ne o us Te st o f ho m o g e ne ity Chi-sq ua re = 4 .3 6 2 7 6 → ho m o g e ne o us Sig nific a nc e p = 0 .8 8 5 9 5 8
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5033
30
48
1330
829
2732
0 10 20 30 40 50 60
Stiegmann (1992)
Hou (1995)
Baroncini (1997)
Sarin (1997)
Masci (1999)
EVLEST
*
*
* * p < 0.05
RANDOMIZED COMPARATIVE TRIALS OF EST & EVLA m e ta -a na lysis o f pub lishe d a rtic le s 1 9 9 2 - 2 0 0 1
RECURRENCE OF VARICES
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Sample Sample sizesize
ChiChi22 P valueP value Effect size Effect size (r)(r)
S tie g m a n n (1 9 9 2 )
129 3.59 0.058 0.16
Ho u (1 9 9 5 ) 134 4.5 0.03 0.18B a ro n c in i (1 9 9 7 )
111 4.65 0.03 0.20
S a rin (1 9 9 7 ) 95 6.03 0.01 0.25M a s c i (1 9 9 9 ) 100 0.43 0.5 0.06
0.98 1.99 4.32
0.21 0.470.98
0.870.240.05
0.29 0.75 1.940.12 0.35 0.83
0.47 0.69 0.92
StiegmannHou
Sarin
Masci
Baroncini
METAOR 0 1 2
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26.7
73.3
34.7
65.3
01020304050607080
EST EVL
Varices recurrence ( + ) Varices recurrence ( - )
To ta l N = 569 Num b e r o f Studie s: k = 5• Po pula tio n e ffe c t s ize r = 0 .1 4 3• 9 5 % c o nfide nc e inte rva l o f po p. e ffe c t s ize : fro m
0 .0 7 4 to 0 .2 1• Expla ine d va ria nc e r-sq ua re = 0 .0 2• Co rre spo nd ing Z in No rm a l Distrib utio n = 3 .4 3• Signific a nc e p = 0 .0 0 0 2 9• Fa il Sa fe N fo r c ritic a l r o f .0 5 = 9• Fa il Sa fe N fo r c ritic a l r o f .1 0 = 2
Pe rc e nta g e o f o b se rve d va ria nc e a c c o unte d fo r b y sa m pling e rro r = 1 0 0 .0 0 % → ho m o g e ne o us Te st o f ho m o g e ne ity Chi-sq ua re = 3 .2 4 → ho m o g e ne o us Sig nific a nc e p = 0 .5 1
RATE OF VARICEAL RECURRENCE AFTER EST & EVLRATE OF VARICEAL RECURRENCE AFTER EST & EVL
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4836 53
304426
513333
1833
171916
4727216
3824
8 14
0 10 20 30 40 50 60
Stiegmann (1992)
Gimson (1993)
Laine (1993)
Lo (1995)
Hou (1995)
Lo (1997)
Baroncini (1997)
Avgerinos (1997)
Sarin (1997)
Hou (1999)
Masci (1999)
EVLEST
*
**
**
* p < 0.05
RANDOMIZED COMPARATIVE TRIALS OF EST & EVLA m e ta -a na lysis o f pub lishe d a rtic le s 1 9 9 2 - 2 0 0 1
RATE OF REBLEEDING
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Sample Sample sizesize
ChiChi22 P valueP value Effect size Effect size (r)(r)
S tie g m a n n (1 9 9 2 ) 129 1.83 0.17 0.11
Gim s o n (1 9 9 3 ) 103 5.84 0.01 0.23La in e (1 9 9 3 ) 77 2.52 0.11 0.18Lo (1 9 9 5 ) 120 4.02 0.044 0.18Ho u (1 9 9 5 ) 134 3.94 0.047 0.17Lo (1 9 9 7 ) 71 2.5 0.11 0.18B a ro n c in i (1 9 9 7 ) 111 0.14 0.7 0.03
A vg 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 0.21Ho u (1 9 9 9 ) 168 4.01 0.045 0.15M a s c i (1 9 9 9 ) 100 0.91 0.33 0.09
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23.09
0.76 1.63 3.5
1.1 2.58 6.65
0.75 2.16 6.34
1.02 2.12 4.76
1.05 2.24 5.43
0.41 1.21 3.630.85 2.44 7.12
0.89 3.86
1.08 1.97 4.06
0.11 0.53 2.29
0.70 2.47 8.93
1.53 1.59 2.07Lo (1 9 9 7 )
Ho u (1 9 9 5 )
Lo (1 9 9 5 )
La ine
Gim so n
Stie g m a nn
Ba ro nc ini
Avg e rino s
Sa rin
Ho u (1 9 9 9 )
Ma sc i
METAOR 0 1 2 3 7
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34
66
24.1
75.9
01020304050607080
EST EVL
Varices re-bleeding ( + ) Varices re-bleeding ( - )
To ta l N = 1185 Num b e r o f Studie s: k = 1 1• Po pula tio n e ffe c t s ize r = 0 .1 2• 9 5 % c o nfide nc e inte rva l o f po p. e ffe c t s ize : fro m
0 .0 8 to 0 .1 6• Expla ine d va ria nc e r-sq ua re = 0 .0 1• Co rre spo nd ing Z in No rm a l Distrib utio n = 4 .3 2• Signific a nc e p = 0 .0 0 0 0 1• Fa il Sa fe N fo r c ritic a l r o f .0 5 =
1 6• Fa il Sa fe N fo r c ritic a l r o f .1 0 = 2Pe rc e nta g e o f o b s e rve d va ria nc e a c c o unte d fo r b y s a m pling e rro r
= 1 0 0 .0 0 % → ho m o g e ne o us Te st o f ho m o g e ne ity Chi-sq ua re = 6 .2 5 → ho m o g e ne o us Sig nific a nc e p = 0 .7 9
RATE OF REBLEEDING AFTER EST & EVLRATE OF REBLEEDING AFTER EST & EVL
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Variceal bleeding
Endoscopy available ?
UGI Endoscopy GlypressinSomatostatin
Octreotide
Oesophageal variceal bleed
Gastric variceal bleed
Band ligation /Sclerotherapy
Uncontrolled Controlled
Baloon tamponade
TIPS / surgery
Banding eradicationprogramme
Gastroesophageal varices
Isolated gastric varices
TIPPS / Butylcyanoacrylate
Treat as oesophagealvarices
YES NO
PROPOSED ALGORITHM FOR THE MANAGEMENT OF VARICEAL
BLEEDING
UK Guide line s , Gut 2 0 0 0