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Abbreviations
CT

computed tomography

GI

gastrointestinal

TIPS

transjugular intrahepatic portosystemic shunt

Ectopic varices are defined as dilated portosystemic collateral veins located in unusual sites other than the gastroesophageal region[1] and constitute 1% to 5% of all variceal bleeds in patients with intrahepatic portal hypertension and 20% to 30% of those with extrahepatic portal hypertension.[2, 3] Ectopic varices represent a clinical challenge because they are difficult to localize, and at present, there are no clear guidelines on the management of ectopic varices due to the diversity of presentation and absence of randomized controlled trials. Recommendations for management are based on various case series and case reports and on individual experience based on local expertise. Hence, algorithms are needed for the treatment and stepwise management of patients with ectopic varices.

Etiology and Prevalence of Ectopic Varices

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

There is considerable heterogeneity in the epidemiology of ectopic varices because of the modality of detection, etiology of portal hypertension, and significant interobserver variability.[4, 5] In a study by Norton et al.,[3] out of 169 patients with variceal bleeding due to ectopic varices, 17% occurred in the duodenum, 17% occurred in the jejunum or ileum, 14% occurred in the colon, 8% occurred in the rectum, 9% occurred in the peritoneum, and a few were located in other rare sites (e.g., the vagina and the ovaries). The authors also found that duodenal varices were common in patients with extrahepatic portal thrombosis on upper gastrointestinal (GI) endoscopy, and 26% of patients with peristomal varices had bled during their study. In another large study of 173 patients, Watanabe et al.[6] found that the mean age of patients with ectopic varices was 62.3 years; 32.9% of patients had duodenal varices, 4% had varices in the jejunum, 1.2% had varices in the ileum, and 3.5% had varices in the colon, and contrary to the previous study, 44.5% of patients had rectal varices and only 5.8% had peristomal varices. Another study by Stephan and Miething[7] showed that the prevalence of duodenal varices was 40% in patients with cirrhosis undergoing angiography. Misra et al.[8] showed an 18% prevalence of ileal varices in patients with cirrhosis undergoing ileocolonoscopy. Colonic varices have been reported in 3.4% of patients with intrahepatic portal hypertension,[9, 10] and anorectal varices have been reported in 10% to 40% of patients with cirrhosis.[11] Stomal varices are particularly common in patients with cirrhotic portal hypertension who have undergone ileostomy after proctocolectomy for inflammatory bowel disease associated with primary sclerosing cholangitis.[12, 13]

In a large series by Sarin et al.,[14] out of 1,128 patients with cirrhotic and extrahepatic portal hypertension, the prevalence of isolated gastric varices was 4.6%. Chawla et al.[15] reported the presence of gallbladder varices in patients with extrahepatic venous obstruction. Occurrence of hemoperitoneum in patients with cirrhosis due to rupture of varices[16-18] (namely, collaterals of the veins of Retzius connecting the superior and inferior mesenteric veins with the lumbar and the lower intercostals veins), venous collaterals connecting the liver with the diaphragm (Sappey veins), and recanalized paraumbilical collaterals[19] draining left portal vein to epigastric veins of the anterior abdominal wall (Cruveillier-Baumgarten syndrome) have been described. Familial cases of ectopic varices have also been reported.[20] A practical classification of ectopic varices based on the site of varices is proposed (Table 1).

Table 1. Classification of Ectopic Varices
LuminalExtraluminal
Isolated gastric varicesIntraperitoneal
DuodenumRetroperitoneal
JejenumUmbilicus
IleumAround the falciform ligament
ColonGall bladder and biliary tree
Rectum and anal canalPerisplenic
PeristomalRight diaphragm
 Ovary
 Vagina

Clinical Presentations of Ectopic Varices

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

Ectopic varices account for up to 5% of variceal bleeds and present with hematemesis or hematochezia depending on the site of the varix. Ectopic varices may also manifest as obscure GI bleeding leading to iron deficiency anemia.

Duodenal Varices

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

The most common afferent vessel for duodenal varices is the inferior pancreaticoduodenal vein (41%), followed by the superior mesenteric vein (10.2%), the duodenal vein (7.7%), and the superior pancreaticoduodenal vein (7.7%). The gonadal (testicular or ovarian) vein was the efferent vessel for duodenal varices in 52.6% cases.[6] Western data have shown that ectopic varices are more common in the duodenal bulb,[21] but Watanabe et al.[6] reported that the most common site of occurrence is in the descending duodenum. In their 57 patients with duodenal varices, 63.2% had a history of esophageal varices, and 35.1% were treated endoscopically. The mean period from endoscopic treatment for esophageal varices to the occurrence of duodenal varices was 2.3 ± 2.1 years. Endoscopy remains the best method of diagnosing duodenal varices. Computed tomography (CT) angiography can detect bleeding duodenal varices if they are massive[22] (Fig. 1).

image

Figure 1. (A,B) Upper GI endoscopic image of duodenal varix with CBD stents in situ in a young boy of extrahepatic portal venous obstruction with portal biliopathy. (C,D) CT angiography showing (C) a sagittal view and (D) a coronal view of paraduodenal collaterals impinging on the duodenum.

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Small Intestinal Varices

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

Small intestinal varices imply the development of varices in the jejunum and ileum. Norton et al.[3] described a prevalence of 17% in jejunal and ileal varices. Jejunal and ileal varices form due to collaterals between the superior mesenteric vein, the inferior mesenteric vein, and the retroperitoneal systemic venous system. A triad of portal hypertension, hematochezia without hematemesis, and previous abdominal surgery characterizes small intestinal varices.[23] Diagnosis is often difficult. According to one study,[24] capsule endoscopy demonstrated small intestinal varices in 8.1% of patients with portal hypertension. Double balloon enteroscopy[25] has both diagnostic and therapeutic potential, hence it is better than capsule endoscopy. Other diagnostic modalities that can be employed are technetium Technetium-99m red blood cell scintigraphy,[26] CT angiography, CT enteroclysis, and laparotomy.

Rectal Varices

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

Rectal varices were first reported in 1954[27] and are probably the most common site of ectopic varices according to two case series. In a landmark study, Hosking et al.[28] showed that in 100 consecutive patients with cirrhosis, the prevalence of rectal varices was 44%. The prevalence of varices increased with the degree of portal hypertension by 19% in patients with cirrhosis without esophageal varices, 39% in patients with esophageal varices that had not bled, and 59% in patients with esophageal varices and bleeding. Hemorrhoids occurred independently of the presence of rectal varices. In their study, 30% of patients had rectal varices and coexistent hemorrhoids. However, it is important to differentiate rectal varices from hemorrhoids. The authors state that rectal varices extend superior to the levator ani and are dilated, tortuous submucosal veins, usually 3 to 6 mm in diameter, that are dark blue in color and do not prolapse into the proctoscope on examination. Another study by Chawla and Dilawari[29] revealed that out of 72 patients with portal hypertension, 56 (77.7%) had anorectal varices. They also noted that 42 of 47 (89.3%) patients with noncirrhotic portal hypertension had anorectal varices and only 14 of 25 (56%) patients of cirrhosis had anorectal varices.

Ganguly et al.[30] first described rectal varices as dilated veins that originated more than 4 cm above the anal verge, were clearly distinct from hemorrhoids, and were not contiguous with the anal columns and/or pectinate line. They also classified rectal varices based on endoscopic grading (grade 1, <3 mm; grade 2, 3-6 mm; grade 3, >6 mm). They also defined lower GI bleeding to be attributed to rectal varices based on three criteria: rectal varices and presence of fresh blood in the rectum, sigmoid colon free of fresh blood, and absence of hemorrhoids or colopathy. They also reported that the incidence of rectal variceal bleeding was 8%. Conflicting reports have been published regarding the occurrence of rectal varices after obliteration of esophageal varices. However, the large case series by Watanabe et al.[6] showed that 73 of 77 (95%) patients with rectal varices had a history of esophageal varices and 67 of 77 (87%) patients had previously undergone endoscopic variceal obliteration for esophageal varices. Rectal varices mainly present with hematochezia. Endoscopy is the principal mode of investigating rectal varices. Endoscopic ultrasound has been found to be a far superior mode of investigation to delineate rectal varices.[31, 32] Figure 2 shows CT images of perirectal collaterals in a patient with cirrhosis with rectal varices.

image

Figure 2. Perirectal collaterals in a patient with cirrhosis with rectal varices. (A) Sagittal reformatted image. (B) Coronal image.

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Peristomal Varices

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

Peristomal varices develop in the mucocutaneous junction of a stoma or in the area proximal to the stoma in patients with portal hypertension.[33, 34] Stomal varices are characterized by a purplish hue around the stoma. The risk factor for the development of peristomal varices is a stoma following a colectomy for ulcerative colitis in patients who have primary sclerosing cholangitis. Percutaneous Doppler ultrasound can detect peristomal collaterals and may be used to guide variceal sclerotherapy. Choi et al.[35] have described the use of multislice helical CT to detect stomal varices that may aid further management.

Hemoperitoneum from Ectopic Variceal Bleed

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

One of the most severe complications of ectopic varices is the rupture of retroperitoneal varices leading to hemoperitoneum. Only 34 cases have been reported in the literature to date. Most of these patients present with hypovolemic shock, with an estimated mortality of 70%. The factors predictive of survival are functional hepatic reserve, the severity of hemorrhagic shock at presentation, and the time taken for early operative intervention and bleeding bleeding control. Figure 3 depicts a suggested algorithm for the management of hemoperitoneum due to ruptured retroperitoneal varices.4

image

Figure 3. Algorithm for the management of hemoperitoneum due to ruptured retroperitoneal varices.

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image

Figure 4. Algorithm for the management of ectopic variceal bleed.

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Management of Ectopic Varices Bleed

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References

Step 1: Resuscitation and vasopressors

Intravascular volume loss is estimated and replaced with crystalloids and packed red cells. According to APASL guidelines,[36] goals are to systolic blood pressure should be maintained at least at 90–100 mmHg, and the heart rate should be maintained below 100 beats/min, with a hemoglobin level around 7–8 g/dL (hematocrit of 21–24). Antibiotic prophylaxis should be initiated at the beginning itself. There are no RCTs to recommend the use of vasoactive drugs in ectopic variceal bleed, but the data on esophageal variceal bleed can be extrapolated and terlipressin should be used.

Step 2: Endoscopic management

Once the patient is hemodynamically stable, emergency upper GI endoscopy should be performed as the first line of investigation. The door to scope time should be less than 6 hours.[36] If it fails to show the source of upper gastrointestinal bleeding, colonoscopy after a rapid preparation with polyethylene glycol solution delivered via a nasogastric tube should be the second step of investigation. If ectopic varices are seen bleeding in form of spurt from or show sign of recent bleed in form of white nipple or an adherent clot (Level of evidence 3b, Grade C), endoscopic management with band ligation[37, 38] or endoscopic sclerotherapy[39, 40] or glue injection should be done. Sato et al[41] showed that while therapeutic efficacy of EVL and sclerotherapy are same, with higher recurrence rates with former. Bhasin et al[42] have demonstrated the use of histoacryl in sclerotherapy of duodenal varix. N-butyl-2-cyanoacrylate (Histoacryl) is a tissue glue monomer that instantly polymerizes and solidifies upon contact with blood. It is potent and need fewer sessions for variceal obliteration compared to other agents. Combination of a sclerosant with thrombin has also been used.[43]

Step 3: Interventional radiology techniques (Rescue therapies)

Transjugular intrahepatic portosystemic shunt (TIPS) is an attractive option after failed endoscopic techniques, as the underlying cause of bleeding ectopic varices is raised portal pressure. In a series by Kochar et al[44] comprising of 28 patients, TIPS achieved 100% initial hemostasis in all patients with ectopic variceal bleed. The rate of rebleed was 21% (5 out of 28). In them, two were due to shunt insufficiency. TIPS with concomitant variceal embolization is preferred to reduce rebleeding.[45]

Balloon occluded retrograde transvenous obliteration (BRTO) is an attractive option. Watanabe et al[6] in their case series described that out of 40 patients with duodenal varices, 50% electively underwent BRTO, 57.1% underwent prophylactic BRTO and 9.5% underwent BRTO as an emergency in bleeding duodenal varices.

Percutaneous transhepatic obliteration (PTO) has been evidenced based on case reports. It means embolisation of ectopic varices using transhepatic approach with coil embolisation of the veins draining into the ectopic varices. Use of PTO in treatment of duodenal varices,[46] rectal varices,[47] jejenal varices using transhepatic portovenous angioplasty and stenting[48] and in treatment of peristomal varices.[49]

Step 4: Surgery

If endoscopic techniques and interventional radiologic procedures fail to control bleeding or are not feasible, surgery is a recommended option provided the underlying good liver function and the local expertise. Surgery is preferred in patients with Child-Pugh 'A' cirrhosis and in patients with an EHPVO. Minor interventions include simple over sewing of the duodenal varices through a duodenotomy,[50] duodenal dearterialization and stapling,[51] circumferential-stapled anoplasty.[52] Major surgical interventions such as shunt surgeries[53] can be undertaken.

References

  1. Top of page
  2. Abstract
  3. Etiology and Prevalence of Ectopic Varices
  4. Clinical Presentations of Ectopic Varices
  5. Duodenal Varices
  6. Small Intestinal Varices
  7. Rectal Varices
  8. Peristomal Varices
  9. Hemoperitoneum from Ectopic Variceal Bleed
  10. Management of Ectopic Varices Bleed
  11. References
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