Endoscopic Classification and Management of Varices

Chapter 7: Endoscopic Classification and Management of Varices


David M. Arner and Abdullah M.S. Al-Osaimi


Introduction


Gastrointestinal (GI) varices represent a serious complication of portal hypertension (PHT) and can lead to life-threatening hemorrhage. Although there are many possible causes of noncirrhotic PHT (images Table 7.1), the most common cause is cirrhosis. Liver remodeling with fibrosis and regenerative nodule formation in cirrhosis increases venous resistance and portal pressure. Intrahepatic vasoconstriction secondary to decreased nitric oxide, and increased endothelin-1 further increases portal pressure.1 Porto-systemic collaterals can form in several anatomic areas along the GI tract. PHT is defined as hepatic venous pressure gradient (HVPG) greater than 5 mm Hg. The HVPG is calculated as the wedged hepatic venous pressure minus the free hepatic vein pressure. Varices do not occur until the HVPG rises above 10 mm Hg, and variceal hemorrhage can occur if HVPG is greater than 12 mm Hg.2,3


Esophageal varices (EVs) and gastric varices (GVs) are the most common PHT-induced GI varices because they provide the largest portosystemic collateral flow via the short and left gastric veins; however, ectopic varices are becoming increasingly recognized on endoscopic and radiologic evaluation (images Fig. 7.1). A variety of treatment options are used for PHT-induced GI varices depending on their location, the acuity of the situation (i.e., bleeding vs. nonbleeding varices), and the patient’s underlying vascular anatomy. Such options include pharmacologic therapy with vasoactive drugs; endoscopic management with band ligation; sclerotherapy; glue injection; stenting; balloon tamponade (BT); or interventional radiologic management with balloon-occluded retrograde transvenous obliteration (BRTO), transjugular intrahepatic portosystemic shunt (TIPS), or venous embolization. With the increased effectiveness and availability of endoscopic and interventional radiologic treatment methods, surgical portosystemic shunt operations are less commonly used but still may play a role in select situations. This chapter reviews endoscopic management of PHT-induced varices.


Esophageal Varices


Esophageal varices exist in approximately 45% of individuals with cirrhosis and correlate with the severity of liver disease (images Fig. 7.2). Child class A patients with cirrhosis have a nearly 40% likelihood of having EVs on routine screening upper endoscopy, whereas Child class C patients with cirrhosis have an approximately 80% probability.4 Varices enlarge at a rate of 4% to 10% annually. Large varices are more likely to rupture, and the 2-year probability of first bleed ranges from 7% among small varices up to 30% with large varices.5,6 Up to 50% of variceal bleeding episodes stop spontaneously. Variceal hemorrhage carries a 6-week mortality rate of 20%, and up to 70% of untreated individuals die within 1 year of their initial hemorrhage. Predictors of hemorrhage include large varices, red marks (red wale sign or cherry red spots) (images Fig. 7.2d), alcoholic cirrhosis, and decompensated Child class B or C cirrhosis.


Screening


Evaluation of EVs has traditionally been performed by esophagogastroduodenoscopy (EGD) (see images Fig. 6.2). Alternative screening modalities have been evaluated, including computed tomography (CT), esophageal capsule endoscopy (ECE), and ultrathin endoscopy. In a prospective study comparing CT with endoscopy, CT had 90% sensitivity but only 50% specificity for identifying large EVs. The sensitivity of detecting GVs by CT was 87% compared with EGD.7 A multicenter study of 120 patients with cirrhotic and noncirrhotic PHT compared ECE with EGD for EV screening and found a sensitivity of 77% and specificity of 86%.8 A meta-analysis by Lu and colleagues showed similar rates of sensitivity and specificity.9 The benefits of CT or ECE over EGD include little discomfort and sedation-less convenience with immediate return to normal activities. Disadvantages of CT include radiation exposure and the possibility of incidental findings of no clinical significance that could prompt further workup and incur additional costs. No serious complications have been reported with ECE, although a low rate of capsular retention has been reported (0.7%–2.2%), usually due to unknown esophageal strictures.10 CT or ECE may be used as treatment modalities among patients who are unwilling to undergo EV screening evaluation with EGD. As opposed to CT and ECE, EGD also affords definitive endoscopic management of varices at the time of the procedure.


Table 7.1 Causes of Noncirrhotic Portal Hypertension
















































Intrahepatic Presinusoidal PHT


Sinusoidal PHT


Extrahepatic Postsinusoidal PHT


Hepatic schistosomiasis


Cirrhosis


Budd-Chiari syndrome


Congenital hepatic fibrosis


Noncirrhotic alcoholic liver disease


Right heart failure


Noncirrhotic portal fibrosis


Infiltrative disorders:


• Amyloidosis


• Systemic mastocytosis


• Malignancy


• Myeloproliferative disorder


Constrictive pericarditis


Nodular regenerative hyperplasia


Suprahepatic IVC thrombosis


Primary biliary cirrhosis, sclerosing cholangitis


Pulmonary hypertension


 


Tricuspid valve regurgitation


Extrahepatic Presinusoidal PHN


 


Portal vein thrombosis


Intrahepatic Postsinusoidal PHN


Superior mesenteric vein thrombosis


Peliosis hepatis


Veno-occlusive disease


Splenic vein thrombosis


Hypervitaminosis A


 


IVC: inferior vena cava; PHT: portal hypertension. (Adapted with modifications from Molina E, Reddy KR. Noncirrhotic portal hypertension. Clin Liver Dis 2001;5:769–787.70)



Another technique evaluated as a possible screening tool for EV is ultrathin endoscopy. Ultrathin endoscopy is a 3.1-mm battery-powered esophagoscope that can be comfortably used without sedation. One study of 28 patients who underwent both ultrathin endoscopy and routine EGD found ultrathin endoscopy to have a sensitivity of 100% and a specificity of 93% for detection of EV, and the ultrathin endoscope was well tolerated.11 The ultrathin esophagoscope does not allow for treatment of varices if identified.


Classification


Several endoscopic classification schemes have been used to grade EVs. In the early 1980s, the Japanese Research Society for Portal Hypertension recommended that endoscopists describe the color, location, and form or size of varices in addition to any possible red marks.12 In 1988, the North Italian Endoscopic Club grouped them into small (F1), medium (F2), and large varices (F3) with or without red marks (images Fig. 7.2). Small varices are minimally elevated above the esophageal mucosa and typically flatten with air insufflation (images Fig. 7.2a). Medium vessels occupy less than one third of the esophageal lumen but do not flatten with insufflation (images Fig. 7.2b). Large EVs occupy greater than one-third the diameter of the esophageal lumen (images Fig. 7.2c). In an effort to further simplify EV classification, recommendations were made at the Baveno I Consensus Conference to categorize varices as either small or large, with a suggested cutoff diameter of 5 mm.13,14 Red marks or nipple signs should still be identified because they represent high-risk features of hemorrhage (images Fig. 7.2d). Most endoscopists use one of the last two classification schemes, and we recommend using the low- or high-risk classification method.


Management: Primary Prophylaxis


Current guidelines suggest a benefit to screening all patients with cirrhosis for EV, and EGD is the most widely used screening method.14 EGD surveillance is recommended at a 1- to 3-year interval based on the patient’s liver disease (compensated or decompensated cirrhosis) and prior findings (presence and grade of varices). Follow-up endoscopies are not required among patients with low-risk varices who are on appropriately dosed beta-blockade therapy (see images Fig. 6.2).


After EGD has been performed, patients with nonbleeding EVs can be risk stratified based on their risk of hemorrhage. Small nonbleeding EVs without high-risk features can be conservatively monitored with surveillance EGD. Small EVs with high-risk features can be managed with medical pharmacologic therapy alone and/or with endoscopic variceal band ligation (EVL). Nonselective beta-blockers is to decrease cardiac output and cause splanchnic vasoconstriction. Patients with nonbleeding large EVs can be treated with beta-blockade therapy, which has been shown to lower rates of first variceal bleeding and mortality.15 However, other treatment options are available for large EVs with high-risk features or among individuals who do not tolerate maximal beta-blockade therapy. Endoscopic treatment modalities primarily include endoscopic sclerotherapy (EST) or EVL.14 TIPS and surgical shunt therapy has also been evaluated for primary prophylaxis.14



Endoscopic Sclerotherapy


Endoscopic sclerotherapy involves direct injection of a chemical sclerosant into the varices. EST has been used as primary prophylactic treatment of EV since the 1980s. Initial trials showed a significant survival benefit in addition to lower rates of first bleeding events.1618 However, further studies did not support these data and actually suggested that EST could provoke bleeding when used as primary prophylaxis.19,20 One study comparing prophylactic sclerotherapy with sham therapy for EV treatment had to be terminated prematurely because the mortality rate was significantly higher in the sclerotherapy group.21 Complications of EST, such as ulcer or stricture formation, perforation, and chest pain, led to the development of alternative treatment options, primarily EVL. Therefore, EST is not recommended as primary prevention of variceal hemorrhage. The technique of EST is described elsewhere in this chapter.


Endoscopic Variceal Ligation


The first reported case of EVL was performed on dogs in 1986 with a 92% success rate. After its safety and efficacy had been assessed, it became available for endoscopic use in humans in 1988 (images Fig. 7.3). Since then, several randomized controlled trials and two meta-analyses have shown EVL to be at least equivalent and possibly superior to nonselective beta-blockers in primary prevention of an initial variceal bleeding episode and to have fewer complications.2226 Complication rates of EVL are low but include chest pain, ulceration, bleeding, stricture formation, and perforation.27 EVL is a recommended treatment option for patients with nonbleeding large varices who cannot tolerate beta-blocker therapy or large varices with high-risk features of hemorrhage. Compared with no active treatment, EVL is associated with a relative risk reduction of first bleeding episode of 64% with a number needed to treat of four to prevent a bleeding episode.28,29



Technique

Banding devices have evolved, and a variety of EVL devices are available for use. Each has a transparent cap that attaches onto the end of the endoscope and carries 1 to 10 stretched bands (images Fig. 7.3). A string that acts as a tripwire attaches the cap to the control handle via the accessory channel of the endoscope. The control handle contains a small wheel that can be rotated to draw the string back and deploy the band(s) when ready. After EVs have been identified, the scope is removed, the banding device is set up and attached to the endoscope, and then the endoscope is readvanced to the most distal varix. With the attached cap placed directly onto the targeted varix, suction is then applied to the varix until it is brought up into the cap. The band is then deployed onto the suctioned varix by turning the trigger wheel. This process can be repeated with the remaining bands on residual varices (images Fig. 7.3b). Banding from the distal end and working proximally is the best method for decompressing varices, allows for complete visualization of the esophagus, and prevents possibly dislodging bands that have already been placed.


Shunt Surgery Operations and TIPS


Although portosystemic shunt surgery is effective at relieving PHT and decreasing EV formation and variceal hemorrhage, studies have shown more episodes of encephalopathy and higher mortality rates associated with this surgery.30 This is likely due to decreasing portal blood flow to the liver.31 TIPS has the same underlying physiologic mechanism as surgical shunt therapy, and because they both carry risks of encephalopathy, liver failure, and procedural complications, neither shunt surgery nor TIPS can be recommended as primary prevention of EV hemorrhage.


Management of Esophageal Varices Hemorrhage


Up to 90% of patients with cirrhosis will eventually develop EV, and nearly one third of them will have an episode of variceal hemorrhage (see images Fig. 6.3). Advances in medical care over the past three decades has dramatically improved survival rates among EV bleeding with a mortality rate of 42% in the 1980s to current rates of 15% to 20%.32,33 Medical therapy should be initiated as early as possible and involves volume resuscitation and hemodynamic support in an intensive care unit setting with goal hemoglobin of 7 to 8 g/dL except in patients with active ongoing bleeding or known ischemic cardiac disease. Care should be taken to not overtransfuse the patient to avoid elevated portal pressures and worsened bleeding. If the patient is having active hematemesis, intubation for airway protection should be strongly considered. Prophylactic antibiotics should be initiated to prevent spontaneous bacterial peritonitis, and octreotide or terlipressin (outside the United States) should be started. Beta-blockers should not be used in the setting of acute hemorrhage. Endoscopic therapy is considered the first-line definitive treatment option and should be performed as early as possible. If unsuccessful or the patient is not hemodynamically stable for upper endoscopy, TIPS or surgical shunting is pursued based on local expertise. As an emergent temporizing measure, balloon tamponade (BT) can be used to control active hemorrhage. BT is effective up to 80% of the time and should be considered if definitive management is not readily available as a temporizing modality.34 Several BT devices are available with the most widely used being the Sangstaken-Blakemore and Minnesota tubes. Esophageal stents have also been evaluated as a tamponade device for uncontrollable EV hemorrhage.


Rebleeding can occur after initial hemostasis and is defined as recurrent variceal hemorrhage after a 24-hour bleed-free interval. Several factors have been associated with rebleeding or failure to control active bleeding and include active spurting varices, Child class C cirrhosis, bacterial infection, portal vein thrombosis, or HVPG greater than 20 mm Hg.35,36


Endoscopic Variceal Ligation


Endoscopic variceal ligation is the most common and recommended treatment method for actively bleeding EV. Approximately 80% to 90% of patients with an active EV bleed achieve hemostasis with EVL; the remaining 10% to 20% of individuals have either unsuccessful hemostasis with EVL or early rebleeding after band ligation.30 The technique used with EVL has been described previously in this section (images Fig. 7.3). When treating an active EV bleed, the endoscopist may start banding at the GE (gastroesophageal) junction and work more proximally. Alternatively, a band may initially be placed on the bleeding or highest risk appearing varix and then additional bands placed from that point. The band causes thrombosis of the varix with necrosis of the mucosa, and the bands typically fall off within a few days with a residual superficial mucosal ulceration that heals and eventually scars. Repeat sessions should be performed at 2- to 4-week intervals until there is complete obliteration of varices.14,32


Endoscopic Sclerotherapy


Endoscopic sclerotherapy is generally used as second-line therapy in an actively bleeding EV or when bleeding precludes adequate visualization to perform band ligation. A variety of sclerosing agents are available, and all appear to be equally effective. The most commonly used sclerosants include sodium morrhuate (5%) and ethanolamine oleate (5%). EST involves initially drawing up the desired amount of sclerosant into a syringe and then attaching it to a needle injector and flushing the injector with sclerosant. The injector is then advanced through the scope channel, and under direct endoscopic visualization, the desired varix can then be injected with 1 to 2 cc of sclerosant and then briefly monitored for bleeding cessation. Varices can be reinjected if needed. Injection adjacent to the varices (paravariceal) is sometimes also performed to assist in thrombosis of the varix by causing inflammation of the surrounding mucosa. EST is typically started at the likely site of active bleeding. If unable to identify this, then it is recommended to inject distally near the GE junction and then advance proximally along the esophagus. A total of 10 to 15 cc of sclerosant is generally used, and both intravariceal and paravariceal injections are effective. EST is a good treatment option when there is significant blood within the esophagus precluding adequate visualization of the bleeding varix. It does come with potential complications as noted previously, primarily esophageal ulcers with possible bleeding, esophageal strictures, perforation, mediastinitis, pericarditis, chylothorax, and acute respiratory distress syndrome.37,38


Esophageal Stents


A few case series have been published on treatment of acute EV hemorrhage with endoscopic stent placement. These stents have been specially developed to not require fluoroscopic guidance. The stent is placed over a guidewire previously passed to the stomach by EGD. The stent has a distal balloon that is inflated with a syringe to ensure proper location in the cardia and lower esophagus.3941 When in location, the stent can be deployed to tamponade the bleeding EV. It can be left in place for up to 14 days and can then be retrieved endoscopically with a hook system.


Self-expandable metal stents (SEMS) have primarily been evaluated as salvage therapy after failure of hemostasis with traditional endoscopic approaches. In a case series of 10 patients who failed initial endoscopic management and had contraindications to TIPS or BT, SEMS was successfully placed in 9 patients. Bleeding was not controlled in three patients, although two of them had GVs.40 A pilot study of 20 patients who failed pharmacologic and endoscopic therapy had SEMS placed with a reported 100% success rate and no significant complications.41 Of the 20 patients, 8 were Child class B and 12 Child class C. The stents were left in place for 2 to 14 days, and bleeding was immediately controlled after placement of the stent in all cases. All of the stents were extracted without complication. Data on SEMS in acute variceal hemorrhage is limited, but it might offer an additional choice to salvage therapy in select patients.


Transjugular Intrahepatic Portosystemic Shunt


TIPS is an effective method of controlling EV bleeding because it significantly lowers the HVPG. TIPS results in a communication between the hepatic vein and one of the intrahepatic portal vein branches, which effectively decompresses the portal system and achieves immediate hemostasis in more than 90% of actively bleeding EV.42 Compared with endoscopic therapy, TIPS reduces rebleeding (19% vs. 47%) but increases encephalopathy (34% vs. 19%) and liver failure without survival or cost benefit.4345 Because of this, TIPS has primarily been used as salvage therapy in cases of EV hemorrhage with inadequate control of bleeding after one or two endoscopic therapy sessions or rebleeding.


A recent randomized multicenter study demonstrated reductions in treatment failure and mortality with earlier use of TIPS among patients with cirrhosis hospitalized for acute variceal bleeding and at high risk for treatment failure. Patients were randomized to either early TIPS (performed within 72 hours) or pharmacotherapy, and EVL with TIPS used as rescue therapy as needed. Among the early TIPS group, there was significant improvement in control of bleeding, decreased rebleeding rates, and a 30% mortality absolute risk reduction. The author of this study concluded that in patients with Child class B or C cirrhosis and HVPG greater than 20 mm Hg, early TIPS may be a reasonable first-line therapy choice in the setting of acute variceal bleeding. Notably, patients with Child class C scores above 13 were excluded from the study.46


Absolute contraindications to TIPS include severe congestive heart failure, severe pulmonary hypertension, severe hepatic failure, multiple hepatic cysts, uncontrolled systemic infection, or unrelieved biliary obstruction. Hepatoma, severe coagulopathy (international normalized ratio >5), thrombocytopenia (<20,000), and portal vein thrombosis are all relative contraindications to TIPS. The MELD (Model of End Stage Liver Disease) score can accurately predict mortality after TIPS.


Surgical Decompression


With the development of additional endoscopic and interventional radiologic approaches to the treatment of actively bleeding varices, surgical decompression of EV bleeding has dramatically declined in the United States and is now only rarely used as rescue therapy. Because of this, many surgeons no longer receive training in shunt operations, and TIPS is generally considered the rescue treatment of choice in most centers.


Gastric Varices


Gastric varices have been reported in 20% to 25% of patients with PHT and have an approximate 25% risk of bleeding within 2 years, with fundal varices carrying the highest bleeding rates14 (images Fig. 7.4). Although GV bleeding occurs less frequently than bleeding from EVs, it tends to be more severe and has higher rebleeding and mortality rates (images Fig. 7.5).14,32


GVs have been classified by Sarin et al as gastroesophageal varices (GOVs) and isolated gastric varices (IGVs) based on their location (images Fig. 7.4).47 GOVs are an extension of EV. Whereas GOV type 1 lesions traverse the lesser curvature, GOV-2 varices extend along the fundus and tend to be more tortuous (images Fig. 7.4a,b; images Fig. 7.5d). IGVs are categorized as IGV-1 lesions if located in the fundus or IGV-2 lesions if located in the body, antrum, or pylorus (images Fig. 7.4c,d; images Fig. 7.5a,b,c).48 IGV-1 are much less common than IGV-2 but have a higher risk of bleeding (images Fig. 7.5d). They should also prompt evaluation of possible splenic vein thrombosis, and if found, splenectomy might be a potential therapeutic option.


As GOV-1 are extensions of EV, they should be treated the same as EV, primarily with EVL. Several therapeutic options have been evaluated for the treatment of high-risk and actively bleeding GVs, including EST, EVL, cyanoacrylate injection, BRTO, and TIPS. High-risk GVs are defined as GOV-2 IGV-1 with stigmata of recent bleeding (i.e., fibrin plug or clot), or any GV in the setting of a recent bleed with no definite stigmata but no identifiable source of bleeding (images Fig. 7.5b,c). Studies have shown glue injection to have higher initial hemostasis rates and lower rebleeding and mortality rates compared with EST and EVL.49,50 Cyanoacrylate glue injection has been shown to have 36% and 46% lower 2- and 3-year rebleeding rates than gastric variceal band ligation.51,52


Cyanoacrylate Injection


Current practice guidelines recommend glue injection with tissue adhesives such as cyanoacrylate as the preferred treatment option for control of GV bleeding with TIPS being a consideration in patients in whom hemorrhage from fundal varices cannot be controlled or in cases of rebleeding14 (see images Fig. 6.3).


The most common cyanoacrylates used are Histoacryl or Glubran (-butyl-2-cyanoacrylate), Dermabond (2-octyl-cyanoacrylate), and Indermil (N-butyl-cyanoacrylate). Cyanoacrylates polymerize rapidly upon contact with weak bases, such as blood, but the polymerization time varies by compound. When injected intravascularly, they solidify and form a cast within the varix. Partial occlusion of the vein occurs immediately, and there is generally total occlusion within hours. The glue cast may remain for months to years. Initial hemostasis rates with glue injection of GV ranges from 90% to 100% with rebleeding rates ranging from 5% to 30%, approximately the same rates as TIPS. GV glue injection carries a 2% to 5% risk of serious complication, including fever, chest pain, embolism, infarction, needle impaction, sepsis, and death. Scope damage from the tissue adhesive can also occur. It should be noted that cyanoacrylates are not approved by the Food and Drug Administration for GV treatment.


Oct 29, 2018 | Posted by in CARDIOLOGY | Comments Off on Endoscopic Classification and Management of Varices
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