29

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