Transcript Slide 1
GI Grand Rounds
USC Gastrointestinal and Liver Diseases
February 10th, 2006
Presented by
Yoshi Makino, M.D.
Moderated by
Dr. Andrew Stolz
Case Presentation
• Patient W.L. is a 57 year old Chinese
male, with PMH sig for chronic Hep B,
cirrhosis and HCC diagnosed in 10/2005,
presenting with hematemesis and melena
x 1 day. Pt denies prior history of UGI
bleed.
Case Presentation
• PMH:
–
–
–
–
Hepatitis B cirrhosis (dx 2004)
HCC (dx 10/2005)
DM, hyperlipidemaa
Otherwise per HPI
• PSH:
– L inguinal hernia repair
• SH:
– Denies EtOH/tobacco/illicit drug use
– Born in mainland China, then lived in Venezuela for 24
years, before moving to United States 15 years ago
• FH:
– Non-contributory: Hep B status unknown
Case Presentation
• Allergies: NKDA
• Medications
– Epivir 100 mg PO daily
– Hepsera 10 mg PO daily
– Aldactone 50 mg PO daily
– Experimental Chemo Agent
• GW572016: EGFR1/EGFR2/HER-2 inhibitor
– Megace/MVI/Folate
• ROS:
– Non-contributory
Physical Exam
• Vital:
– T 97.8 / P 121 / R 20 / BP 120/64
– Orthostatics (+)
• Gen: thin, cachectic male, A+O x 4 in NAD
• HEENT: temporal wasting, no conjuctival pallor
• Cardiac: sinus tachy
• Lungs: CTA(B)
• Abdomen:
– Mod firm, distended, with shifting dullness
– Non tender, (+)BS
• Ext: 2+ pitting edema to BLE
• Rectal: normal tone, (+)melena, OB(+)
• Skin: No spider angiomas seen
• Neuro: No asterixis, no focal deficits
Laboratories (1/24/06)
10.1
9.6
279
30.9
6.8
MCV
RDW
PT
INR
PTT
PTT rat
84.9
19.2
18.3
1.52
30.9
8.6
26.8
214
Alk P
TProt
Alb
TBili
DBili
133
99
40
5.9
23
1.1
317
6.5
2.7
2.1
0.9
AST
ALT
309
208
171
EGD Images (1/25/06)
EGD Images (1/25/06)
EGD Images (1/25/06)
EGD Results (1/25/06)
• 4 columns of Grade 1 Esophageal Varices
with no stigmata of recent bleeding
• Large, grape-like, plump gastric varices,
with one large varix with a “white nipple”
sign
• No active bleeding nor oozing noted
• Mild portal hypertensive gastropathy
• Normal duodenal bulb
CT Images
• Insert magical slide show here…
CT Results (1/3/2006)
• Compared with 11/1/2005 study
• Large heterogeneous enhancing lobulated liver
mass occupying the entire R lobe of the liver,
and medial segment of L lobe of the liver:
increased in size by 50%
• Tumor invasion of right and main portal veins
• Cirrhosis with multiple collaterals, Portal HTN
• R inguinal hernia, fluid filled
Hospital Course
• Pt was subsequently transferred to USC
University Hospital on 1/26/2006
• TIPS considered for decompression of
gastric varices, but not advised due to
large tumor burden, portal vein invasion,
and overall poor prognosis
• Hospice care discussed with patient, and
patient discharged on 2/2/2006
Gastric Varices
Outline
•
•
•
•
Overview of Gastric Varices
Vascular Anatomy
Classification
Diagnostic Modalities
– Endoscopic
– CT/MRI
• Therapeutic options
– Endoscopic
– Interventional Radiology
– Surgery
Overview of Gastric Varices
• Gastric varices (GV) are a well known
complication of both non-cirrhotic and
cirrhotic portal hypertension
• In general, gastric varices bleed less
frequently than esophageal varices
• However, when they bleed, bleeding is
usually severe
Epidemiology
• Gastric varices can be found in 15-20% of
patients with portal hypertension
• Lifetime bleeding rate of roughly 25%
• Overall mortality rate of 30-52%
Kim T et al. Hepatology 1997.
• In a prospective study of 568 patients with
portal hypertension, Sarin et al found that GVs
formed at an annual incidence rate of 9%
Sarin SK et al. Hepatology 1992.
Risk Factors for Bleeding
• Risk factors for bleeding may include
– Specific caliber and length
– Source of venous collaterals involved
– Advanced liver disease
Kim et al. Hepatology 1997.
• Degree of portal hypertension appears to
be less of a factor, with GVs often
bleeding at portal pressure gradients of
<12 mmHg
Tripathi et al. Gut 2002.
Vasculature Involved
• Afferent Veins
– Left gastric vein (LGV)
– Posterior gastric vein (PGV)
– Short gastric vein (SGV)
• Efferent Veins
–
–
–
–
Esophageal veins (EV)
Gastrorenal shunt (GRS: 85% of IGV)
Left inferior phrenic vein (LIPV: 10% of IGV)
Left pericardiacophrenic vein (LPCPV: 5% of IGV)
Chikamori et al. Abdominal Imaging 2005.
Formation of Varices in Portal HTN
• LGV to EV to azygous v.
– Traditional model for
esophageal varices, can
also result in the formation
of gastric varices
• SV to GRS to LRV to IVC
– Significant portal HTN can
also lead to reversal of flow
in the splenic vein, resulting
in transgastric shunts
(usually GRS)
Willmann et all. BMJ 2003.
Splenic Vein Thrombosis
• Sinistral (left-sided) portal HTN due to splenic
vein thrombsis (SVT) is an often cited but less
common cause of gastric varices
• Incidence of gastric varices in patients with
isolated SVT ranges from 17% to 55%
• SVT should be suspected in patients with
– History of pancreatitis with newly diagnosed GI bleeding
– splenomegaly in the absence of cirrhosis
– Isolated gastric varices
Weber and Rikkers. Word J. Surg. 2003.
Splenic Vein Thrombosis
• Risk factors for SVT include
– Chronic pancreatitis (48-65%)
– Pancreatic carcinoma (9-29%)
– Other causes: adenopathy from metastatic carcinoma,
lymphoma and iatrogenic (following surgery such as
splenectomy and gastrectomy)
• Pathophysiology
– The splenic vein is posterior to and in direct contact with
the pancreas
– Pancreatic inflammation is believed to trigger clot
formation in the splenic vein
Weber and Rikkers. Word J. Surg. 2003.
Splenic Vein Thrombosis
• Prevalence of SVT
– In patient with chronic pancreatitis, the prevalence of
SVT by ultrasonography ranges from 4% to 45%
• Incidence of SVT
– In a prospective study of 266 patients with chronic
pancreatitis, Bernard et al found the overall incidence
rate of major splanchnic vein thrombosis to be 13%
• Splenic vein 8%
• Portal vein 4%
• Superior mesenteric vein 1%
Bernades et al. Dig Dis Sci. 1992.
Formation of Varices in SVT
Weber et al. World J Surg 2003.
Histologic Findings
• Fundamentally, GVs differ from EVs by location
– EVs form in both the lamina propria and submucosa
– In contrast, GVs form in the submucosa
• This difference make rupture of GVs less frequent than
EVs
• However, when do GVs rupture, they penetrate the
muscularis mucosa and lamina propria, leading to more
massive bleeding
Hashizume M. JGH 2004.
L
Willmann et all. BMJ 2003.
Classification of Gastric Varices
• Gastro-oesophageal varices (GOV)
– Usually develop from the left gastric vein
– GOV1: extend from esophageal varices across the
gastroesophageal junction, extending 5 cm or less
– GOV2: extend from esophageal varices into the fundus
• Fundic varices (IGV)
– Usually develop from the short gastric and posterior gastric veins or
via direct anastomoses with retroperitoneal veins
– IGV1: varices found only in the fundus
– IGV2: isolated non-fundic varices
• GOV1 represents 75% of gastric varices
• IGV1 result in the most serious bleeding
Sarin SK et al. Hepatology 1992.
Diagnostic Modalities
• Endoscopy
– Gastric varices can appear as “grape-like” clusters or
“serpiginous” varices that resemble gastric folds
– The bluish color that is characteristic of esophageal
varices is usually absent
– However, conventional endoscopy frequently misses
submucosal lesions
• gastric varices: sensitivity of 48% and a specificity of 50%
• esophageal varices: sensitivity of 94% and a
specificity of 17%
• (in a series of 23 patients, using EUS as a gold standard)
Liu JB et al. Radiology 1993.
Non-invasive Imaging
• Multi-detector row CT (MDCT) is an emerging
minimally invasive technique for detective GVs
• Allows for visualization of small visceral
vessels by offering faster acquisition times with
less motion artifact
• In a series of 22 patients by Willmann et all,
MDCT was compared against the present old
standard of EUS with comprable detection rates
Willmann et all. Gut 2003
MDCT 3D Reconstruction
Willmann et all. Gut 2003
Treatment Options
•
•
•
•
•
Endoscopic Therapy
TIPS
B-TRO
Surgery
Plan B
Endoscopic Therapy
• Endoscopic therapeutic options for
gastric varices remains limited in the
United States
• While band ligation is moderately
effective in GOV1, rebleeding rates still
approach 50%
• Endoscopic injection sclerotherapy (EIS)
is largely ineffective, as the high flow
rates in gastric varices “wash-out” the
sclerosant
Sarin SK. Gastro Endo 1997.
Does Treating EVs worsen GVs?
• Theoretically, obliteration of esophageal varices should
lead to increased pressure elsewhere in the portal
system
• Indeed, sclerotherapy of EVs has been shown to
transiently worsen portal hypertensive gastropathy
(PHG)
Sarin et al. Am J Gastroenterol 2000.
• Furthermore, secondary GV’s following both EVL/EIS
appeared at a rate of 8.8%
• However, overall sclerotherapy of EVs improves GVs
– post EVL: resolution of GOV1 in 50%
– post EIS: resolution of GOV1 in 61.5%
Sarin et al. J Hepatol 1997.
Endoscopic Sclerosants
• Ethanolamine Oleate
– Agglutinating platelets
– Destroying the endothelial cells of shunts and varices
– Promotes clot formation
• N-butyl-2-cyanoacrylate (Histoacryl)
– Adhesive similar to super glue (which is made of ethyl-2cyanoacrylate)
– Polymerize on contact with basic substances such as
water or blood to form a strong bond
– Histoacryl is typically mixed 1:1 with Lipiodol to prevent
premature solidification in the endoscope
Sclerotherapy
• Sarin studied 71 patients with gastric variceal
sclerotherapy over an 11 year period
• Outcomes
– Primary hemostasis in acute bleeding: 66.7%
– Variceal obliteration: 71.6% (with repeated elective sclerotherapy)
– Variceal obliteration by GV type
• GOV1: 94.4%
• GOV2: 70.4%
• IGV1: 41%
– Rebleeding rates
• GOV1: 5.5%
• GOV2: 19%
• IGV1: 53%
Sarin SK. Gastrointest Endosc 1997.
Combination EVL and EIS
• In a study by Arakai et al, 56 patients with
gastric varices were treated with combination
band ligation and polidocanol injection
• Extremely favorable results were obtained
– 100% control of acute bleeding
– 12.5% variceal recurrence rate
– 3.6% rebleeding rate
• However, most cases were GOV1, and
applicability to all types of gastric varices
remains questionable
Arakai et al. Endoscopy 2003.
Combination EVL and EIS
Movie not included due to Copyright.
Movie may be viewed at:
Goff JS. VHJOE 2005.
http://www.vhjoe.com/Volume4Issue1/4-1-4New.htm
Histoacryl Injections
• Endoscopic tissue adhesive injection was first
applied in the treatment of bleeding gastric
varices by Gotlib and Zimmermann, and
Ramond et al. in 1986.
• The rapid rate of activation of the adhesive
appears to overcome the high flow rates within
the large varices
• Overall, Histroacryl is effective in controlling
bleeding
– Primary hemostasis achieved in 94-97%
– Rebleeding rates of roughly 20-30%
– Long term survival is difficult to assess
Mahadeva et al. Am J of Gastro 2003.
Histoacryl: Complications
• The most severe complication is the occurrence
of systemic embolization
• Risk factors for systemic embolization
– Large volume injection
– Shunt between the portal system and the pulmonary vein
(rare)
• Major complications include
–
–
–
–
Cerebral infarct in 2 patients
Splenic infarction
Pulmonary embolism
Inflammatory tumor in pancreatic tail
See A. Gastroenterol Clin Biol 1986. / Yu et al. Gastro Endo 2005. /
Witthoft et al. Z Gastroenterol 2004. / Sato et al. J Gastroenterol. 2004.
Ethanolamine and Gastric Varices
• A novel approach has been proposed by Kojima et al.,
using Ethanolamine Oleate and Iopamidol (EOI)
concurrently with vasopressin
• Vasopressin is infused at 0.4 u/min continuously from
30 minutes before to 6 hours after sclerotherapy
• To counteract systemic vasoconstriction, a
nitroglycerin patch is also applied to the patient
• Under both endoscopic and fluroscopic guidance, using
iopamidol as the contrast agent, EOI is injected to fill
the varices (15 ± 10.5 mL)
• As the injection needle is removed, the site is sprayed
with thrombin glue to seal the puncture site
Kojima et al. J Gastro Hepato 2005.
Ethanolamine/Fibrin Dual Needle
Kojima et al. J Gastro Hepato 2005.
Ethanolamine: Outcomes
• Vasopressin presumably reduces portal pressure and
blood flow, resulting in improved retention of the
sclerosant (EOI)
• In a series of 30 patients by Kojima et al., favorable
results were obtained
–
–
–
–
Primary hemostasis achieved in 28/30 patients (93.3%)
Cumulative rebleeding rate at 1, 3, and 5 years: 13%, 19%, 19%
Mortality at 1, 3, and 5 years: 31%, 54%, 59%
Average number of EIS sessions: 2.3 ± 1.1
• Side effects were minimal
– 8 patients with mild fevers
– 6 patients developed ulcerations at the injection site
Kojima et al. J Gastro Hepato 2005.
Gastric Varices with Endoclip
Arantes and Albuquerque. Gastrointest Endosc 2005.
TIPS
• Transjugular Intrahepatic Portosystemic Shunt
(TIPS) in a human was first created in Germany
in 1988
• Since, TIPS has become the standard therapy
for secondary prevention of bleeding
esophageal varices
Boyer T. Gastro 2003.
• TIPS is also used to treat gastric varices in
Europe and the United States, however the
clinical utility of TIPS in this setting is debatable
TIPS: Contraindications
Absolute
Relative
•Primary prevention of variceal
bleeding
•Congestive heart failure
•Multiple hepatic cysts
•Uncontrolled systemic infection
or sepsis
•Unrelieved biliary obstruction
•Severe pulmonary hypertension
•Hepatoma, especially if central
•Obstruction of all hepatic veins
•Portal vein thrombosis
•Severe coagulopathy
(INR >5)
•Thrombocytopenia of less than
20,000/cm3
•Moderate pulmonary
hypertension
AASLD Guidelines 2005
Boyer and Haskal. Hepatology. Vol. 41, No. 2, 2005.
TIPS: Technique
• A needle catheter is introduced into the hepatic vein
typically via the right transjugular vein
• The catheter is thenwedged in a peripheral branch of
the right hepatic vein
• Wedged hepatic venography is then performed with
carbon dioxide gas, demonstrating the location of the
main, left and right PVs
• Colapinto needle is advanced through the wall of the
right hepatic vein and into the right PV
• After an elevated pressure gradient is confirmed,
intrahepatic parenchymal tract is dilated with an 8- or
10-mm high-pressure balloon.
• Finally a self-expanding metallic stent, such as the
Wallstent, is deployed
Novelli et al. http://www.emedicine.com/radio/topic764.htm
TIPS: Procedure
From: http://ndovasc.rsmu.ru/ portal.htm
TIPS: Outcomes
• TIPS has shown great success in achieving
immediate short-term control of gastric variceal
bleeding, with hemostasis in 90-96% of cases
Barange. Hepatology 1999.
Chau et al. Gastro 1998.
• However, long term outcomes are poor
–
–
–
–
Rebleeding in 31% after 1 year
Stenosis of TIPS in 95% after 2 years
Mortality rate of 41% after 1 year
Treatment may worsen encephalopathy
Barange. Hepatology 1999.
Arai et al. J Gastroenterol 2005.
TIPS: The Problem
• Central to the problem is the fact that gastric
varices can form at portal pressures of
<12 mmHg
• TIPS must compete with large gastro-renal
shunts, reducing its efficacy
• Response can be predicted by the type of
gastric varix
– GOV1 respond more favorably (>80% hemostasis)
– GOV2 respond less favorable (26% to 70% hemostasis)
– IGV1 and IGV2 are usually associated with larger gastrorenal shunts
Barange et al. Hepatology 1999.
TIPS: Competing with SR Shunt
L Gastric v. Gastric Varices
Splenorenal Shunt
Post-TIPS, with persistant
L Gastric v. filling
From: Ford et al. Cadiovasc Intervent Radiol 2004.
IVC Filter + Coil Embolization
Simon Nitinol vena cava
filter deployed in L
gastric v.
Two 20 mm diameter
coils deployed
Occlusion of L gastric v.
confirmed
From: Ford et al. Cadiovasc Intervent Radiol 2004.
B-TRO
• Balloon-occluded Retrograde Transvenous
Obliteration (B-TRO) is an interventional
radiolgy technique for embolizing gastric
varices through a gastrorenal shunt.
• First introduced by Kanagawa et al. in 1991, it is
increasingly used in Japan but has seen limited
use in Europe and the United States
B-TRO: Technique
• B-TRO uses a 6.5 Fr occlusive balloon catheter
placed through either the femoral or internal
jugular vein, to the left renal vein and into the
gastro-renal shunt (GRS)
• The balloon is inflated, and contrast is injected
retrograde into the GRS
• Any collateral drainage (usually via the inferior
phrenic vein) is embolized
• Patients also usually receive 4000 U of
haptoglobin IV to reduce risk of hemolysis and
renal failure
B-TRO: Technique
• Once isolation of the shunt is confirmed,
a 5-10% mixture of ethanolamine oleate with
iopamidol (EOI) is injected to fill the GRS (up to
50 cc may be required)
• The EOI and balloon are left in place for at least
1 hour (even over-night in some protocols)
• The balloon is deflated after cessation of blood
flow within the shunt is confirmed by
angiography
• A contrast-enhance CT is performed 1 week
after the procedure; if recanalization is seen, BTRO is repeated
B-TRO: Diagram
Adapted from Takuma et al. CGH 2005.
B-TRO: Images
Pre-embolization: Collaterals
Post-embolization: Isolation of GV
Ninoi et al. AJR Am J Roentgenol 2005.
B-TRO: Results
• Prophylactic B-TRO shows excellent
results
– 5-year recurrence rate of GVs: 2.7%
– 5-year rebleeding rate from GVs: 1.5%
(78 patients with a median follow-up of 700 days)
Ninoi et al. AJR 2005.
• Prophylactic B-TRO increases survival
– Cummulative survival at 1, 3 and 5 years
• B-RTO (17 patients): 94%, 85%, 39%
• Control (17 patients): 71%, 41%, 22%
(p=0.04 34 patients, prospective, non-randomized study)
Takuma et al. Clin Gastro Hepato 2005.
B-TRO: Results
• B-TRO has been applied in patients presenting
with acute bleeding
– In a series of 11 patients by Arai et al, after either
spontaneous of endoscopic hemostasis was achieved, BTRO was performed within 24 hours
– Obliteration of GVs was achieved in 10 out of 11 patients
(90.9%)
Arai et al. J Gastroenterol 2005.
• Other benefits include
– Improvement in both Child-Pugh score, possibly due to
increased hepatic blood flow
– Reduction of hepatic encephalopathy by occluding a
major shunt
Takuma et al. Clin Gastro Hepato 2005.
B-TRO: Worsening Varices
• Obliteration of the gastro-renal shunt results in
elevation of pressures elsewhere in the portal
system
• Worsening of esophageal varices is seen in
roughly 50% of patients post-B-TRO
• Presence of esophageal varices prior to B-TRO
is a significant risk factor
• Post B-TRO Rates of EVs at 1, 2 and 3 years
– Patients with prior EVs: 35%, 66% and 91%
– Patients without EVs: 21%, 21% and 29%
(p < 0.01)
Ninoi et al. AJR 2005.
Surgical Management
• Indications
– Failure of endoscopic therapy and salvage of for
TIPS
– Noncirrhotic portal hypertension, in particular
with extrahepatic portal vein thrombosis
Surgical: Shunt Procedures
• Non-selective
– Decompresses the entire portal tree by diverting all flow
away from the portal system
– i.e. Portacaval shunt
• Selective
– decompressed variceal system, but maintains sinusoidal
perfusion via a hypertensive superior mesenteric-portal
compartment
– i.e. Distal splenorenal shunt (Warren)
• Partial
– Partial portocaval small diameter interposition shunt
(Sarfeh)
Wolff M and Hirner Arch Surg 2003.
Surgical: Obliteration
• Gastrectomy
– IGV1 (Fundic): fundic portion of the stomach is
resected with mechanical stapling to eradicate
intramural varices.
– IGV2 (Cardiac): proximal gastrectomy
• Devascularization
– Gastric devascularization and splenectomy
(Hassab’s procedure)
– Gastroesophageal devascularization and
splenectomy (Hassab-Paquet procedure)
Hassab MA. Surgery 1967.
When All Else Fails… This Fails Too
• Primary hemostasis in 30 to 90 percent
• Complications
– Esophageal rupture
– High risk of rebleeding following balloon deflation
– Aspiration pneumonia secondary to inbaility to
clear oral secretions
Chojkier and Conn. Dig Dis Sci 1980.
Hunt et al. Dig Dis Sci 1982.
Name the Tube
Sengstaken-Blakemore Tube
Minnesota Tube
Types of Tamponade Balloons
• Sengstaken-Blakemore tube
– 250 cc gastric balloon and an esophageal
balloon
– single gastric suction port
• Minnesota tube
– 250 cc gastric balloon and an esophageal
balloon
– esophageal suction port and gastric suction port
• Linton-Nachlas tube
– a single 600 cc gastric balloon
Questions… Comments?
Makino et al. observed high rates of hemostasis
and lower overall mortality when balloon
tamponade tubes were tied to USC football
helmets vs. placebo (UCLA helmet)
Special Thanks:
Terri Wiksell of Centocor
Special Acknowledgement:
Bianca Harabour
This presentation is available at:
http://www.doctoryoshi.com
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