Recent advance in management of esophageal variceal bleeding Joint Hospital Surgical Grand Round 25 January, 2014 Tse Pui Ying Nicole (TMH) EV bleeding: commonly encountered emergency in daily practice Introduce a new device

M/58 We put in a metal stent for rupture esophagus HBV carrier, child’s B cirrhosis Admitted x Upper GI Bleeding OGD: bleeding esophageal varices, banding performed Rebleeding few hours later failed to stop bleeding with endoscopic method (banding and sclerotherapy) Put in Sengstaken tube  complicated with esophageal tear We put in a metal stent for rupture esophagus Patient has no more bleeding ? Metal stent can stop variceal bleeding? Why failed endoscopic mean? Profuse bleeding, friable mucosa,

Recent advance in management of esophageal variceal bleeding Self-Expanding Metal Stents (SEMS) Refractory bleeding: 10% (ongoing bleeding despite pharmacological and endoscopic treatment) [4]

Current management Haemetemesis/Melena Resuscitation Endoscopy (OGD) Confirm esophageal variceal bleeding Variceal ligation (Banding) / Sclerotherapy Failure Success Balloon Temponade: - Sengstaken-Blakemore tube Prevent rebleeding: Vasoconstrictor

Current management SEMS Haemetemesis/Melena Resuscitation Endoscopy (OGD) Confirm esophageal variceal bleeding Variceal ligation (Banding) / Sclerotherapy Failure Success Balloon Temponade: - Sengstaken-Blakemore tube Prevent rebleeding: Vasoconstrictor SEMS

SEMS SX-Ella DANIS stent [10] Removable, covered, self- expanding Control variceal bleeding by tamponade effect Placed at most 2 weeks Gold markers: loops at both end (for repositioning and stent removal) Radiopaque markers: at both ends and midpoint Ella-CS, Hradec Kralove, Czech Republic Conform to esophageal peristalsis  reduce risk of stent migration Protective pressure valve that does not allow gastric balloon to inflate against resistance

SEMS Stent insertion Mean duration of procedure: 10 (+/- 6 minutes) [7] Balloon port Gastric balloon Guidewire White lock Blue lock Stent Endoscopy also confirm whether bleeding stopped Distal portion of stent delivery system withdrawn to allow inflation of gastric balloon Wire port [14]

Guidewire delivered into stomach Stent delivery device advanced over the guidewire Gastric balloon inflated with 100ml of air Withdraw whole system until resistance felt (i.e. balloon impacted at cardia) Thus anchoring the distal end of stent during deployment Gastric balloon deflated and stent delivery system withdrawn Endoscopy or X-ray to confirm positioning [14]

Stent Removal Also can look for any immediate re-bleeding? Through endoscopic procedure and a foreign body retractor Grasp the proximal loop of the stent Blunt ended plastic sheath advanced over the wire  constrain the stents  without exerting shear force [5]

SEMS VS Sengstaken tube - Advantages Can be left in situ as long as 2 weeks Cannot be removed by an agitated patient Allow detailed and repeated endoscopic examination Less risk of pulmonary aspiration Definite treatment: TIPS, lap azygoportal disconnection, band ligation, interventional radiography-guided coiling, transplant Maximum 2 weeks: minimize risk of migration and wall injury or reaction [9] SEMS: Standardized expansion power and pressure to esophageal wall

SEMS Limitation Complication Gastric varices cannot be controlled [9] Do not exert a lasting effect Complication Stent migration into stomach Esophageal ulcer Esophageal tear Prevent migration of stent into stomach: (minimize by delayed the second endoscopy for 3 mins (give time for full stent expansion and optimal integration with esophageal wall) Definitve therapy: e.g. EVL, TIPS, transplant SEMS

Recent studies on SEMS Control of acute bleeding (Time frame: 120 hours (5 days)), failed if [12] Death Fresh hematemesis / >=100ml fresh blood aspirated Hypovolaemic shock Hb drop >3g/dL within any 24 hour Success of stent placement Duration of placement Stent migration Complication Mortality Recurrent bleeding: i.e. secondary prophylaxis Definition according to Baveno criteria

Success in stent placement Control of bleeding duration No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 6.7% esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 2.9% esophageal tear 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 10% esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 12.5% compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 6.25% esophageal ulcer 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

Case series, not controlled trial Small sample size No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 1 esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 1 esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 1 compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) Case series, not controlled trial Small sample size Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

Failure (delivery system error) gastric balloon rupture No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 1 esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 1 esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 1 compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) Failure (delivery system error) gastric balloon rupture failed inflation All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

c.f. Balloon tamponade: 80% Failure: GV bleeding No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 1 esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 1 esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 1 compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) c.f. Balloon tamponade: 80% Failure: GV bleeding failed stent deployment All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

How to decide?? No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 1 esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 1 esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 1 compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) How to decide?? All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

Immediate repositioning No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 1 esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 1 esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 1 compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) Immediate repositioning All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

Esophageal tear Esophageal ulcer No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 6.7% esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 2.9% esophageal tear 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 10% esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 12.5% compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 6.25% esophageal ulcer 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) Esophageal tear Esophageal ulcer All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

c.f. Usual 6 week mortality rate: 15-20% No. of patient Success in stent placement Control of bleeding duration Stent migration Local complication mortality Hubmann et al. 2006 [3] 15 100% 5 days (1-14) 25% 1 esophageal tear 20% (60 days) Zehetner et al. 2008 [4] 34 97% 18% 29% (60 days) Wright et al. 2010 [5] 10 90% 70% 9 days (6-14) N/A 1 esophageal ulcer 50% (42 days) Dechene et al. 2012 [6] 8 88% 11 days (7-14) 0% 1 compression of left main bronchus 75% (60 Days) Zakaria et al 2013 [7] 16 93.75% 87.5% 2-4 days 37.5% 25% (42 days) Febienne et al 2013 [8] 9 89% 1-5 days 22% 77% (42 days) c.f. Usual 6 week mortality rate: 15-20% Reason of death liver failure, multi-organ failure, uncontrolled bleeding High mortality rate Selection bias (more severe underlying liver disease) Further study to rule out ? Related to stent Delayed / Unrecognized complication All are case series Location of study: Austria, UK, Egypt, Swiss, Stent migration: reposition Overlap between first 2 studies + further management, child grading, cause, etc

Discussion – practical aspect How to monitor any re-bleeding/complication after stent insertion ? Daily OGD/CXR ? One single size of stent fit for every patient Need expertise for stent placement Most study: either inserted with radiographic or endoscopic guidance Some study: daily CXR for stent position, bleeding control by clinical, blood test Further management after stent removal? TIPS, EVL, surgical shunt, etc Pressure that it can exert? Theorectically how much pressure to arrest EV bleeding? How is it different from commonly used stents in malignant stricture Attempted in HK?

SEMS Limitation of study Future study Limited number of study available Not a controlled study Small sample size Only short term follow up (up to 60 days) Future study Need randomized trial Larger sample size Long term follow up Treatment for EV bleeding with esophageal tear Applicability of data to other currently available fully covered SEMS As initial first line treatment (in emergency room) As definitive therapy

Conclusion SEMS is a recent advance in management of refractory esophageal variceal bleeding Considered as a alternative to balloon temponade safe and effective treatment in limited data low complication rate Satisfactory rate of bleeding control & stent deployment need further study Practical aspect: duration, monitoring, expertise

Reference Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46: 922-38. Gin-Ho Lo. Management of acute esophageal variceal hemorrhage. Kaohsiung J Med Sci 2010; 26: 55-67. Hubmann R, Bodlaj G, Czompo M, et al. The use of self-expanding metal stents to treat acute esophageal variceal bleeding. Endoscopy 2006; 38: 896–901. Zehetner J, Shamiyeh A, Wayand W, et al. Results of a new method to stop acute bleeding from esophageal varices: implantation of a self-expanding stent. Surg Endosc 2008; 22:2149–2152. Wright G, Lewis H, Hogan B, et al. Self-expanding metal stent for complicated variceal hemorrhage: experience at a single center. Gastrointest Endosc 2010;71:71–78. Dechene A, El Fouly AH, Bechmann LP, et al. Acute management of refractory variceal bleeding in liver cirrhosis by self-expanding metal stents. Digestion 2012;85:185–191. Zakaria MS, Hamza IM, Mohey MA, et al. The fist Egyptian experience using new self-expandable metal stents in acute esophageal variceal bleeding: Pilot study. Saudi J Gastroenterol 2013; 45: 485-8. Fabienne C. Fierz, Walter Kistler, Volker Stenz, et al. Treatment of esophageal variceal hemorrhage with self- expanding metal stents as a rescue maneuver in a swiss multicentric cohort. Case Rep Gastroenterol 2013; 7: 97-105. Fuad Maufa and Firas H. Al-Kawas. Role of Self-Expandable Metal Stents in Acute Variceal Bleeding. Internalional Journal of Hepatology 2012; 418369. Angels Escorsell and Jaime Bosch. Self-Expandable Metal Stents in the Treatment of Acute Esophageal Variceal Bleeding. Gastroenterology Research and Practice 2011; 910986. Vivek Kumbhari, Payal Saxena, Mouen A, et al. Self-Expandable Metallic Stents for Bleeding Esophageal Varices. The Saudi J of Gastroenterology 2013; 1434 Roberto de Franchis, on behalf of the Baveno V Faculty, Revising consensus in portal hypertension: Report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension, Journal of Hepatology 2010; 53: 762-768 National Institute for Health and Clinical Excellence. Stent insertion for bleeding oesophageal varices. 2011; April László Benk M.D. New minimal invasive therapeutic options in the management of acute and recurrent esophageal bleeding, 2007

Thank You

[13]

Should we use it? Weak evidence 1st stage 2nd stage SEMS SEMS Failure Failed EVL/EIS: profuse bleeding, prevoius intervention SEMS Failure SEMS

The Danis stent is larger in diameter and the expansion force has been adjusted to work efficiently against bleeding varices, but not to harm the esophageal tissue. The larger diameter is sufficient to fit every patient. The pressure exerted by the stent has been evaluated in animal model and later with clinical experience to be sufficient and safe

[9]

Management Pre-primary prophylaxis (Prevention of formation of varices) Non-selective beta-blockers: no evidence to prevent formation of varices OGD: Should be screened for varices at diagnosis Primary prophylaxis (prevention of first variceal hemorrhage) Non-selective beta blocker: Recommended OGD: Esophageal variceal ligation (EVL) recommended Repeated every 1-2 weeks till complete obliteration Secondary prophylaxis (prevention of rebleeding) Combination of nonselective beta blockers + EVL TIPS: recurrent variceal haemorrhage Transplant Non-endoscopic method in predict varices: plt count, fibroteest, spleen size, PV diameter, transient elastography (point prevalence of medium/large varices: 15-25%) Rebleeding rate in untreated individual: 60% within 1-2 years  need secondary prophylaxis

Contraindication of stent When remove stent Bind time to let pharmcological therapy to work When elective procedure a/v or expertise a/v Convert emergency procedure to elective Contraindication of stent Stricture Esophageal tumor Previous radiation Body weight <40kg Risk of stent complication like esophageal rupture Protective pressure valve  does not allow gastric balloon to inflate against resistance if gastric balloon inflate wrongly in esophagus  safety balloon at tip of delivery system is inflated

Migration Pressure it exert Monitoring Covered stent Uncovered stent Wait for 3 minutes for full expansion Optimal integration with esophageal wall Uncovered stent Metal wire to dense: impringe on varices with pin point pressure Metal wire not close: varices may squeeze out between wire and can’t exert temponade effect Pressure it exert Not specific mentioned Radial pressure Evaluate in animal model and clinical experience to be sufficient and safe Monitoring CXR daily OGD alt day

Treat the symptom, not underlying cause (liver failure) Treat esophageal varices Physical: banding, sengstaken, SEMS Chemical: sclerosant, superglue (cyanoarcylate monomer) Treat underlying disease Best medical treatment Further treatment Late stage Further treatment has its own risk and complication, e.g. TIPS (seldom do) Nutrition, lactulose, antibiotic, avoid hepatotoxic drug, medication, etc In our study: EVL, TIPS, shunt surgery, transplant