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  • 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
  • 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.
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • « 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
  • 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
  • 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
  • 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
  • « 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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