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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
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.
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)
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
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
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
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
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
● 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
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
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
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
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
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
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
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
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
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
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
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 )
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
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
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
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
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
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
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
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
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