VASCULAR LESIONS

ANGIOECTASIA

Angioectasia (AE) of the colon is a distinct clinical and pathologic entity.^1–3 It is the most common vascular abnormality of the GI tract and probably the most frequent cause of recurrent or chronic lower intestinal bleeding in persons older than 60 years of age.⁴ AEs are probably acquired with aging, and there does not appear to be a gender predominance. In contrast to congenital or neoplastic vascular lesions of the GI tract, AEs are not associated with lesions of the skin or other viscera. However, when patients with vascular lesions of the colon are aggressively studied with angiography or enteroscopy, concomitant lesions may be seen in the small intestine in approximately 10% of patients.^3,5,6 AEs almost always are confined to the cecum or ascending colon, usually are multiple rather than single, and usually are smaller than 10 mm in diameter. They are seldom identified by the surgeon at operation or by the pathologist using standard histologic techniques, but usually they can be diagnosed by angiography; colonoscopy (Figs. 36-1 and 36-2); or, as recently shown, helical CTA.⁷

Figure 36-1. Endoscopic image of an angioectasia (AE) in the ascending colon. This AE has a typical coral reef-like pattern of small vessels distorting the mucosa and submucosa. A tortuous submucosal vein, which is the earliest stage in the development of an AE, probably is present among the linear vessels intersecting the ectasia.

Figure 36-2. Endoscopic images of multiple angioectasias (AEs) in the ascending colon of an older adult patient who presented with recurrent bouts of lower intestinal bleeding. AEs can be single or, as shown here, multiple and of various shapes and sizes. Draining veins are seen adjacent to the AEs.

The roles of computed tomography (CT) and magnetic resonance imaging (MRI) for vascular lesions of all types are evolving but are certain to increase as these sophisticated modes of diagnosis become more widely available; it is also clear that conventional angiography at present is more important for therapy than for diagnosis. To determine the precise nature of a vascular lesion, histologic examination, with or without injection studies of the vasculature, is necessary. In one report in which histologic confirmation of vascular lesions was not performed, AEs reportedly occurred distal to the hepatic flexure in 46% of patients⁸; review of tissue sections from supposed AEs in the small bowel or left colon revealed histologic changes different from those of AEs in the right colon (personal review by S. J. Boley and L. J. Brandt).

Bleeding from cecal AEs was first shown in 1961 by intraoperative angiography and has since become well recognized, especially after the introduction of selective angiography and colonoscopy for identifying the source of intestinal bleeding (see Chapter 19).⁸ In older literature, AEs and diverticulosis were considered the two most common causes of severe lower GI hemorrhage in older adults; however, more recent publications have cited AEs and diverticulosis to be responsible for 3% to 37% (mean: 10%) and 15% to 55% (mean: 30%) of major lower intestinal bleeding episodes, respectively (see Chapters 19 and 117).⁹ The problem of attributing bleeding to one or the other cause, when bleeding from the lesion is not demonstrated by endoscopy or by extravasation of contrast material on radiologic imaging studies, is compounded by the frequency and coexistence of these disorders without bleeding in people older than 60 years of age. The prevalence of diverticulosis is estimated to be as high as 50% in the population older than age 60; mucosal and submucosal AEs of the right colon can be found by injection studies of colons removed at surgery in more than 25% and 50%, respectively, of patients in this age range without evidence of bleeding.^1,10 In large series of colonoscopic examinations, AEs have been seen in 0.2% to 2.9% of nonbleeding persons and 2.6% to 6.2% of patients evaluated specifically for occult blood in the stool, anemia, or hemorrhage.^3,11–12 In a patient being studied for GI bleeding, in whom the site of active bleeding is unproven, the only basis for determining that an identified ectasia or diverticulosis is responsible for bleeding is the indirect evidence provided by the patient’s course after ablation or resection of the suspected lesion. It is unusual for AEs found incidentally to bleed, and an AE, even in a patient with a history of bleeding, cannot be assumed to be the cause.¹³

Bleeding from AEs typically is recurrent and low grade, although approximately 15% of patients present with massive hemorrhage. The nature and degree of bleeding frequently vary in the same patient with different episodes: Patients may have bright red blood, maroon stools, or melena on separate occasions. In 20% to 25% of episodes, only tarry stools are passed, and in 10% to 15% of patients, bleeding is evidenced solely by iron deficiency anemia, with stools that are intermittently positive for occult blood.⁴ This spectrum reflects the varied rate of bleeding from the ectatic capillaries, venules, and arteriovenous communications, depending on the developmental stage of the lesions (see later). In more than 90% of instances, bleeding stops spontaneously.

In 1958 E. C. Heyde described what is still a controversial association of AEs, GI bleeding, and aortic stenosis; aortic valve replacement had even been recommended for “Heyde’s syndrome” when bleeding could not be managed adequately. Numerous reports of Heyde’s syndrome appeared in the literature; subsequent analysis¹⁴ and many studies,¹⁵ however, failed to support the association. This association recently has been suggested again¹⁶ in a retrospective study in which the frequency of aortic stenosis was 31.7% in patients with “AVMs” compared with 14% in the general population; severe aortic stenosis was also more likely in the group with intestinal vascular lesions. The additional postulate has been offered that deficiencies of the largest forms of von Willebrand factor multimers (von Willebrand syndrome, type 2A) result in hemostatic abnormalities that may predispose preexisting AEs to bleed.¹⁷ Preoperative deficiency of these multimers reverses after aortic valve replacement,¹⁸ but the general recommendation to replace the aortic valve to control bleeding from AEs seems premature now that a variety of transendoscopic and angiographic means are available to ablate AEs.

Pathology

Histologic identification of AEs is difficult unless special techniques are used.¹ Although usually less than one third of lesions are found by routine pathologic examination, almost all can be identified by injecting the colonic vasculature with silicone rubber, dehydrating the cells with increasing concentrations of ethyl alcohol, clearing the specimen by immersing it for 24 hours in a bath of methyl salicylate, and then viewing the specimen by dissecting stereomicroscopy (Fig. 36-3).¹ In a study using these methods, surgically resected colons were analyzed and found to have one or more mucosal AEs measuring 1 mm to 1 cm in diameter. AEs were usually multiple, and in this study, all were located within the cecum and ascending colon; the most distal one was 23 cm beyond the ileocecal valve.¹

Figure 36-3. A, A specimen of resected colon that has been injected with silicone rubber, but not cleared (see text for details). Stereomicroscopy reveals the honeycomb-like pattern of normal colon crypts. B, Coral reef appearance of an angioectasia (AE) in an injected, but not cleared, colon. The normal crypts are seen surrounding the AE. C, Injected, cleared, and transilluminated colon, showing a mucosal ectasia surrounded by normal crypts with ectatic venules leading to a large, distended, tortuous underlying submucosal vein.

(A and B, From Mitsudo S, Boley SJ, Brandt LJ, et al. Vascular ectasias of the right colon in the elderly: a distinct clinical entity. Hum Pathol 1979; 10:589; C, from Boley SJ, Sammartano RJ, Adams A, et al. On the nature and etiology of vascular ectasias of the colon: Degenerative lesions of aging. Gastroenterology 1977; 72:650, with permission.)

Microscopically, mucosal AEs consist of ectatic, distorted, thin-walled venules, capillaries, and arterioles, vessels that are lined by endothelium, and, infrequently, a small amount of smooth muscle. The earliest abnormality is the presence of dilated, tortuous, submucosal veins (Fig. 36-4A), often in areas where mucosal vessels appear normal. More extensive lesions show increasing numbers of dilated and deformed vessels traversing the muscularis mucosa and involving the mucosa (see Fig. 36-4B and C) until, in the most severe lesions, the mucosa is replaced by a maze of distorted, dilated vascular channels (see Fig. 36-4D). Enlarged arteries and thick-walled veins occasionally are seen in advanced lesions, in which the dilated arteriolar-capillary-venular unit has become a small arteriovenous fistula because of loss of prearteriolar sphincter function. Large thick-walled arteries are more typical of congenital arteriovenous malformations.

Figure 36-4. Histopathology of angioectasia (AE). A, Large distended veins filling the submucosa with a few dilated venules in the overlying mucosa. This appearance is the hallmark of an early AE. The black material in the lumen of the vessels is Microfil. B, A more advanced AE lesion in which dilated tortuous veins in the submucosa extend into the mucosa. C, A further stage in the development of an AE lesion in which the ectatic vessels are disrupting and replacing the mucosa. D, A late stage of AE shows total disruption of the mucosa with replacement by ectatic vessels. Only one layer of endothelium separates the lumen of the cecum from those of the dilated vessels. (Hematoxylin and eosin stain, ×50.)

(From Boley SJ, Sammartano RJ, Adams A, et al. On the nature and etiology of vascular ectasias of the colon: Degenerative lesions of aging. Gastroenterology 1977; 72:650, with permission.)

Pathogenesis

The previously described studies using injection and clearing techniques indicated that AEs are acquired lesions associated with aging and that they represent a unique clinical and pathologic entity.¹ That AEs are common lesions associated with aging is supported by their frequent identification at colonoscopy in older adults and in injected colons resected from older patients with no history of bleeding.^1,11 Boley postulated that the likely cause of AEs is partial, intermittent, low-grade obstruction of submucosal veins at the site where these vessels pierce the muscular layers of the colon¹ (Figs. 36-5 and 36-6). He further suggested that repeated episodes of transiently elevated pressure during muscular contraction and distention of the cecum over many years conceivably result in dilation and tortuosity of the submucosal vein and, later, of the venules and capillaries of the mucosal units that drain into it. Finally, he postulated that the capillary rings dilate, the precapillary sphincters lose their competency, and a small arteriovenous fistula is produced. The latter is responsible for the “early-filling vein,” which was the original angiographic hallmark of this lesion (Fig. 36-7). Prolonged increased flow through the arteriovenous fistula can then produce alterations in the arteries supplying the area and in the extramural veins that drain it. This developmental concept of the cause of AEs was based on the finding of (1) a prominent submucosal vein, either in the absence of any mucosal lesion, or underlying only a minute mucosal AE supplied by a normal artery; (2) dilation of the veins, starting where they traverse the muscularis propria (see Fig. 36-5); and (3) previous studies showing that venous flow in the bowel may be diminished by increases in colon motility, intramural tension, and intraluminal pressure.¹⁹ Following this logic, the prevalence of AEs in the right colon can be attributed to the greater tension in the cecal wall compared with that in other parts of the colon, according to LaPlace’s principle: T ∝ pDP (where T is tension, D is diameter, and P is intraluminal pressure).

Figure 36-5. Vasa rectum and accompanying vein traversing the cecal muscularis propria. Compression of the vein is the functional anatomic explanation for intermittent, partial low-grade venous obstruction. (Elastin-von Gieson, ×50.)

(From Boley SJ, Sammartano RJ, Adams A, et al. On the nature and etiology of vascular ectasias of the colon: Degenerative lesions of aging. Gastroenterology 1977; 72:650, with permission.)

Figure 36-6. Proposed concept of the development of cecal angioectasia. A, Normal state of vein perforating muscular layers. B, With muscular contraction or increased intraluminal pressure, the vein is partially obstructed. C, After repeated episodes over many years, the submucosal vein becomes dilated and tortuous; this is the stage that accounts for the slowly emptying vein on mesenteric angiography. D, Later, the veins and venules draining into the abnormal submucosal vein become similarly involved. E, Ultimately, the capillary ring becomes dilated, the precapillary sphincter becomes incompetent, and a small arteriovenous communication is present through the ectasia; this stage accounts for the early filling vein seen on mesenteric angiography.

(From Boley SJ, Sammartano RJ, Adams A, et al. On the nature and etiology of vascular ectasias of the colon: Degenerative lesions of aging. Gastroenterology 1977; 72:650, with permission.)

Figure 36-7. Angiography of angioectasia (AE). A, Superior mesenteric artery arteriogram from a patient with AEs shows two densely opacified, slowly emptying, dilated tortuous cecal veins (arrows). Note the late visualization of the ileocolic vein after other veins have cleared. B, Arterial phase of the same arteriogram shows two vascular tufts (thick arrows) and two early-filling veins (each shown by a pair of thin arrows).

(From Boley SJ, Sprayregen S, Sammartano RJ, et al. The pathophysiologic basis for the angiographic signs of vascular ectasias of the colon. Radiology 1977; 125:615, with permission.)

An alternative concept for the development of AEs is based on the demonstration that AEs have been shown to express vascular endothelial growth factor (VEGF) and its receptors along the endothelial lining in surgical specimens from patients who have undergone colectomy for recurrent bleeding²⁰; this indicates a proliferative phase of angiogenesis. VEGF and VEGF receptor 1 have been shown to be up-regulated by hypoxia²¹ and therefore a role has been suggested for hypoxia in the pathogenesis of AEs. Further research still is needed to clarify the pathophysiology of AEs.

Diagnosis and Management

Management of bleeding AEs consists of three phases: (1) diagnosis; (2) conversion of an emergency situation to an elective one by control of acute bleeding; and (3) definitive treatment of the AE by colonoscopic ablation or surgical removal. The diagnostic approach to colonic AEs is essentially the same as that for lower intestinal bleeding in general and includes radionuclide bleeding scans; colonoscopy; angiography; and, to exclude the small intestine as a site of bleeding, push enteroscopy and wireless capsule endoscopy (WCE). WCE is a relatively new diagnostic technique that enables visualization of the entire small intestine, and rarely the very proximal colon where colonic AEs are found. WCE is particularly useful for evaluating patients with obscure and occult GI bleeding.²² WCE has been shown to be superior to push enteroscopy in the evaluation of patients with small intestinal bleeding, yielding a diagnosis in 55% to 75% of patients with obscure bleeding that required transfusions, most common of which was angiodysplasia.^23,24 Radionuclide scans are used to determine whether a patient is actively bleeding and, if so, to localize the site (see Chapter 19). Although angiography previously had been the principal means of identifying AE as the source of bleeding, colonoscopy currently is the preferred method. Helical CTA is a relatively new, sensitive, specific, and well-tolerated technique to diagnose colonic AEs, although prospective studies comparing CTA with other imaging techniques are necessary.⁷

The endoscopist’s ability to diagnose the specific nature of a vascular lesion is limited by the similar appearance of different types of lesions. AEs, spider angiomas, hereditary hemorrhagic telangiectasia, angiomas, the focal hypervascularity of radiation colitis, ulcerative colitis, Crohn’s disease, ischemic colitis, certain infections (e.g., syphilis, Pneumocystis), hyperplastic and adenomatous polyps, and malignancies, including lymphoma and leukemic infiltrations, can all, on occasion, resemble each other (Table 36-2). Because traumatic and endoscopic suction artifacts may resemble vascular lesions, all lesions must be evaluated on insertion of the colonoscope, rather than during withdrawal. Pinch biopsy samples of vascular lesions obtained during endoscopy usually are nonspecific; therefore, the risk of performing biopsies of these abnormalities is not justified.

Table 36-2 Lesions That May Be Confused with Angioectasias on Endoscopy

Vascular Lesions

Arteriovenous malformations Angiomas Phlebectasias Spider angiomas Telangiectasias Varices Venous stars

Nonvascular Lesions

Trauma

Polyps

Adenomatous

Hyperplastic

Lymphoid

Neoplasms

Leukemic infiltration

Lymphoma

Because the appearance of vascular lesions is influenced by a patient’s blood pressure, blood volume, and state of hydration, such lesions may not be evident in those with severely reduced blood volumes or shock; thus accurate evaluation may not be possible until red cell and volume deficits are corrected. Meperidine also may diminish the prominence of some vascular abnormalities (e.g., AEs and the telangiectasias of hereditary hemorrhagic telangiectasia); use of meperidine, therefore, should be minimized and its effects reversed by naloxone so that vascular lesions can be detected accurately. Such a masking effect does not seem to occur with fentanyl. Naloxone has been shown to enhance the appearance of normal colonic vasculature in approximately 10% of patients and cause existing AEs to appear (2.7%) or increase in size (5.4%) (Fig. 36-8).²⁵ For these reasons, naloxone is an important adjunctive medication for patients undergoing endoscopic evaluation for lower intestinal bleeding. Cold water lavage of the colon, as is sometimes done to cleanse the luminal surface of debris during colonoscopy, also may cause underlying AEs to disappear transiently.²⁶

Figure 36-8. Endoscopic images showing progressive changes in the appearance of a cecal angioectasia (AE) after the administration of naloxone. Subtle at first, the AE becomes a pale and then deep red, fan-shaped obvious vascular lesion.

(From Brandt LJ, Spinnell M. Ability of naloxone to enhance the colonoscopic appearance of normal color vasculature and colon vascular ectasias. Gastrointest Endosc 1999; 49:79.)

Angiography is used to determine the site and nature of lesions during active bleeding and can identify some vascular lesions even after bleeding has ceased. The three reliable angiographic signs of AEs are a densely opacified, slowly emptying, dilated, tortuous vein; a vascular tuft; and an early-filling vein (see Fig. 36-7).²⁷ A fourth sign, extravasation of contrast material, identifies the site of bleeding when bleeding volume is at least 0.5 mL/minute but is not specific for AE. The slowly emptying vein (see Fig. 36-7A) persists late into the venous phase, after the other mesenteric veins have emptied. Vascular tufts (see Fig. 36-7B) are created by the ectatic venules that join the mucosal AE and the submucosal vein. They are seen best in the arterial phase; are usually located at the termination of a branch of the ileocolic artery; appear as small candelabra-like or oval clusters of vessels; and still are seen in the venous phase communicating with a dilated, tortuous, intramural vein. The early-filling vein is seen in the arterial phase within four or five seconds of injection (see Fig. 36-7B); it is not a valid sign of AE if vasodilators such as papaverine or tolazoline (Priscoline) have been used to enhance the study. When the lesion is bleeding, intraluminal extravasation of contrast material usually appears during the arterial phase of angiography and persists throughout the study. Extravasation identifies the site of active bleeding, but in the absence of other signs of AEs, it suggests another cause for the bleeding.

Management of incidental (nonbleeding) AEs detected by colonoscopy is expectant. The natural history of colonic AE is benign in healthy, asymptomatic people, and the risk of bleeding is small.^13,28,29 In such cases, endoscopic therapy is not warranted.³⁰

Bleeding can be controlled endoscopically or angiographically in most patients, thereby avoiding the morbidity and mortality of emergency operation. In decades past, intra-arterial embolization and vasopressin were used to control upper and lower GI bleeding, respectively. Vasopressin, given via an angiographic catheter placed into the feeding splanchnic vessel, arrested hemorrhage successfully from AE in more than 80% of patients in whom extravasation was demonstrated. Now, superselective microcoil embolization has largely replaced intra-arterial vasopressin infusion for the treatment of lower intestinal hemorrhage.³¹ Such embolization is highly effective and safe but complicated by ischemic events in approximately 5% of cases.³² Vasopressin still is recommended, however, when intestinal lesions are diffuse throughout the bowel or when superselective catheterization is not possible.³²

Hormonal therapy, using estrogens in combination with progestins, has been used to treat patients with a variety of vascular lesions of the GI tract, in an attempt to reduce or terminate bleeding. The mechanisms by which such agents work are not known, although procoagulant effects and endothelial injury are popular theories. Although one long-term observational study³³ showed that combination hormonal therapy stopped bleeding in patients with occult GI bleeding of obscure origin (likely to have resulted from small bowel angiodysplasia), current studies do not support the use of these agents to prevent rebleeding from GI angiodysplasia.³⁴ It is likely that hormonal therapy affects different vascular lesions differently and that vascular lesions in the small intestine may respond differently to such treatment than the same lesions in the colon; no study of hormonal therapy has been done for known colonic AEs.

A novel therapy for AEs, and perhaps other vascular lesions in the gastrointestinal tract, is the use of antiangiogenic factors. Thalidomide was developed in the 1950s as a sedative, sleeping pill, and antiemetic for pregnant women, but it soon became notorious for causing phocomelia and other malformations in the newborn.³⁴ In 1994, D’Amato and colleagues reported that thalidomide inhibited VEGF and basic fibroblast growth factor-mediated angiogenesis, which led to further characterization and subsequent clinical applications of its antiangiogenic activity.^35,36 Recent data suggest the mechanism for its antiangiogenic effect is related to reduced expression of integrin genes and resulting decreased cell-cell surface interactions and response to angiogenic cytokines.³⁷ Several case reports and case series have described the successful use of thalidomide to treat life-threatening or refractory bleeding from intestinal AEs and Crohn’s disease with refractory bleeding.^38–42 After treatment with thalidomide for three months, substantial reductions in the number, size, and color intensity of AEs were observed by WCE.³⁹

Of the available antiangiogenic biologic therapies, most information regarding clinical efficacy and toxicity is available for bevacizumab (Avastatin), a humanized monoclonal antibody against VEGF that is effective against colon and renal cancers and that also has a strong antiangiogenic activity.⁴³ Curiously, dose-dependent nasal and GI bleeding is observed in up to 59% of patients during treatment, possibly caused by a loss of vascular integrity as a result of bevacizumab-induced endothelial-cell shedding in highly regenerative mucosal tissues with active angiogenesis. It is unclear why some antiangiogenic substances like bevacizumab cause mucosal bleeding and others like thalidomide do not; this disparity effect may be related to the phase of angiogenesis that is antagonized, or might reflect a particular strong antiangiogenic activity. Although VEGF-based antiangiogenic therapy is a promising therapy, the issue of aggravation of bleeding from vascular lesions needs further study. A more detailed understanding of the angiogenic cascade and how antiangiogenic substances act within it will be needed to resolve this issue.

Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser^3,6,44,45; endoscopic sclerosis¹¹; monopolar⁴⁶ and bipolar⁴⁷ electrocoagulation; heater probe⁴⁷; and, recently, hemoclips in combination with cautery,⁴⁸ endoscopic band ligation,⁴⁹ and argon plasma coagulation (APC)⁵⁰ have been used to ablate vascular lesions throughout the GI tract and can be used to control active bleeding (Fig. 36-9). Control of bleeding has been obtained with a variety of endoscopic thermal means in 47% to 88% of cases,³ and no technique has been established as superior to the next.¹¹ Severe delayed bleeding occurs in 5% of patients with colonic AEs after thermal therapy.⁴⁶ Recurrent bleeding from colonic AEs appears to be reduced after these therapies, but more than one treatment session is usually necessary.⁴⁷ Rebleeding can be expected to increase with time after the procedure and has been seen in 28% to 52% of patients over a follow-up period ranging from 15 to 36 months.³

Figure 36-9. Endoscopic images showing angioectasia and diverticulosis of the colon. A (upper), A single angioectasia (AE) nestled among diverticula in the ascending colon of an older adult man with lower intestinal bleeding. AEs and diverticula are probably the two most common causes of major recurrent lower intestinal bleeding in older adults, therefore finding them together in the same patient is not unusual. A (lower), The lesion after treatment with argon plasma coagulation. B (upper), Multiple AEs in the ascending colon. B (lower), AEs after treatment with a heater probe. Not every vessel must be ablated for the bleeding to resolve. C (upper), A solitary AE. C (lower), The heater probe is being used to ablate the lesion.

In preparation for endoscopic ablation of vascular lesions, aspirin and aspirin-containing drugs, other nonsteroidal anti-inflammatory agents, anticoagulants, and antiplatelet agents should be withdrawn at least one week to 10 days before the procedure, if possible. During colonoscopy, care should be taken not to distend the cecum fully because the wall would be further thinned and the risk of perforation increased. Aspiration of some luminal gas just before thermal therapy adds a measure of safety. Again, use of meperidine should be minimized and, if it is used, its effects should be reversed by naloxone before treatment in order to detect vascular lesions more accurately.

Right hemicolectomy is indicated when AE has been identified by either colonoscopy or angiography and when therapy by either or both of these two modalities is unsuccessful, cannot be performed, or is unavailable. The presence or absence of diverticulosis in the left colon does not alter the extent of colonic resection in this circumstance; only the right half of the colon is removed, but it is important that the entire right half of the colon be removed to ensure that no AEs are left behind. If the site of bleeding (and its cause) is not identified, and bleeding recurs or is continuous, recent experience suggests that a subtotal colectomy is appropriate surgical therapy. Older literature emphasized that the morbidity and mortality rates of a right hemicolectomy (which would remove all bleeding AEs and 50% to 70% of bleeding diverticula) followed by a left hemicolectomy (if bleeding recurred postoperatively) were less than the morbidity and mortality rates of a subtotal colectomy. More recent literature suggests that morbidity and mortality rates of a subtotal colectomy are not statistically different from those accompanying a “blind” hemicolectomy, that is, when the bleeding site is not identified.^51,52 In one surgical series and review, mortality for subtotal colectomy was 0% to 40% with a rebleeding rate of 0% to 8%, and mortality and rebleeding rates for a directed limited colectomy were 2% to 22% and 0% to 15% respectively⁵¹; in contrast, the mortality and rebleeding rates for a blind limited colectomy were 20% to 57% and 35% to 75%, respectively. In another surgical series, frequency of bowel movements after limited colectomy was 2.4 per day, a number not substantially different from the 3.5 bowel movements per day documented after subtotal colectomy.⁵²

HEREDITARY HEMORRHAGIC TELANGIECTASIA (OSLER-WEBER-RENDU DISEASE)

This autosomal dominant familial disorder is characterized by telangiectasia of the skin and mucous membranes, as well as recurrent GI bleeding.^53–55 The pathogenesis may relate to mutations of the endoglin (ENG) and activin receptor–like kinase 1 (ALK-1) genes, which have an important role in determining the properties of endothelial cells during angiogenesis (see later).⁵⁶ Lesions typically are noticed in the first few years of life, and recurrent epistaxis in childhood is characteristic of the disease. By age 10, about half of patients have had some GI bleeding. Severe hemorrhage is unusual before the fourth decade and has a peak incidence in the sixth decade. In most patients, bleeding presents as melena; bright red blood per rectum and hematemesis are less frequent. Hematochezia in a patient with hereditary hemorrhagic telangiectasia (HHT) suggests bleeding from a source other than telangiectasia. Bleeding is chronic and may be severe; patients may receive more than 60 transfusions in a lifetime. A family history of the disease has been reported in 80% of patients with HHT but is less common in those who bleed later in life. Telangiectasias usually are present on the lips, oral and nasopharyngeal membranes, tongue, and periungual areas; lack of involvement of these sites casts suspicion on the diagnosis (Fig. 36-10).

Figure 36-10. Telangiectasias of hereditary hemorrhagic telangiectasia. A, Multiple telangiectasias on the nose and lips. Telangiectasias of varying size and shape in the proximal gastric body (B), antrum (C), and duodenal bulb (D).

(From Wilcox CM. Atlas of Clinical Gastrointestinal Endoscopy. Philadelphia, Pa: WB Saunders; 1995. p 123.)

The clinical diagnosis of HHT currently requires the presence of at least three of four relevant clinical criteria. These so-called Curaçao criteria include epistaxis (spontaneous and recurrent nosebleeds); telangiectases (multiple at characteristic sites, e.g., lips, oral cavity, fingers or nose); visceral lesions (e.g., pulmonary, hepatic, cerebral, spinal, or GI vascular malformations); and family history (a first-degree relative with HHT).⁵⁷ The clinical diagnosis of HHT can be confirmed by molecular genetic analysis. In most cases, HHT is caused by mutations in one of the two known HHT genes. Mutations of the ENG lead to type 1 HHT.⁵⁸ The ENG gene is located on chromosome 9q34.1 and encodes for endoglin, a type III transforming growth factor-β (TGF-β) receptor. Type 2 HHT is attributed to mutations of the activin A receptor type II-like 1 gene (also termed activin receptor-like kinase-1 (ALK1),⁵⁹ which codes for the ACVRL1 protein, a type I TGF-β receptor. Both receptors are members of the TGF-β receptor family, are expressed predominantly on vascular endothelium, and play essential roles in maintaining vascular integrity. Evidence for the existence of two other as yet unidentified HHT genes has been reported.^60,61 Despite genotypic heterogeneity in HHT, the clinical expression of the different HHT genotypes appears to be the same. HHT and nonhereditary intestinal AE (see earlier) are characterized by increased production of VEGF. High serum levels of VEGF, which also correlate with severity of bleeding, are found in patients with HHT.^62,63 Vascular involvement of the liver is common in HHT and frequently is asymptomatic; hepatic manifestations during the course of the disease are seen in 8% to 31% of patients. Typical clinical presentations of liver involvement are high-output heart failure resulting from arteriovenous shunting, portal hypertension, and biliary tract disease.^64,65 Serious complications, including liver failure necessitating liver transplantation, have been reported. Telangiectasias occur in the colon but are more common in the stomach and small bowel, where they also are more apt to cause major bleeding.

Telangiectasias are seen easily on endoscopy, although in the presence of severe anemia, blood loss, or hypotension, they transiently may become less obvious or even invisible; after correction of blood volume and blood pressure, they become prominent again. Evaluation by conventional angiography or newer techniques such as helical CTA⁶⁶ and MRA may be unrevealing or demonstrate arteriovenous communications, conglomerate masses of abnormal vessels, phlebectasia, and aneurysms.⁶⁷ Angiography may be misleading when it demonstrates multiple vascular abnormalities because some of these lesions may be in the mesentery rather than in the bowel and are not potential sites of GI blood loss.

Grossly, the telangiectasias are the size of millet seeds and typically appear as cherry red, smooth hillocks. Pathologically the major changes involve the capillaries and venules, but arterioles also may be affected. Lesions consist of irregular, ectatic, tortuous blood spaces lined by a delicate single layer of endothelial cells and supported by a fine layer of fibrous connective tissue. No elastic lamina or muscular tissue is present in these vessels, so they cannot contract; this property may explain why the lesions tend to bleed. Arterioles show intimal proliferation and commonly have thrombi in them, suggesting vascular stasis. In contrast to the thinned venules of AEs, venules are abnormally thick in HHT; have prominent, well-developed longitudinal muscles; and apparently play a major role in regulating blood flow in telangiectasias.⁶⁶

Many forms of treatment have been recommended for telangiectasias, including estrogens,⁶⁸ aminocaproic acid,⁶⁹ endoscopic thermal ablation,^6,45 and resection of involved bowel. Endoscopic ablation, including the use of the APC and thermal contact devices, is most promising when lesions are within reach of the endoscope and not too diffuse. Endoscopic therapy may be performed during active bleeding or between bleeding episodes and has reduced the need for emergency bowel resection. Long-term follow-up studies are necessary to evaluate the ultimate efficacy of the various forms of therapy.

Bevacizumab, the humanized monoclonal antibody against VEGF discussed earlier, was used to treat a 47-year-old woman with HHT and severe liver involvement. Significant clinical improvement was observed three months after initiating treatment with reversal of cholestasis, resolution of cardiac failure and ascites, and improvement in nutritional status. A marked reduction in liver vascularity and liver volume also were seen over a six-month interval.⁷⁰

PROGRESSIVE SYSTEMIC SCLEROSIS (see also Chapter 35)

Vascular lesions are a prominent feature of progressive systemic sclerosis, especially in the calcinosis, Raynaud’s phenomenon, esophageal dysmotility, scleroderma, and telangiectasia (CREST) variant.⁷¹ Sites most frequently involved by these telangiectasias are the hands, lips, tongue, and face, but gastric, intestinal, and colorectal lesions have been reported. These tiny lesions may be the source of occult or clinically significant bleeding and are best treated, if possible, by endoscopic thermal ablation.⁷²

GASTRIC ANTRAL VASCULAR ECTASIA (WATERMELON STOMACH) AND PORTAL HYPERTENSIVE GASTROPATHY

Gastric antral vascular ectasia (GAVE), or watermelon stomach, describes a vascular lesion of the gastric antrum that consists of tortuous, dilated vessels radiating outward from the pylorus-like spokes of a wheel and resembling the dark stripes on the surface of a watermelon.⁷³ This lesion may cause acute hemorrhage and chronic occult bleeding. Its cause is unknown, although it has been proposed that gastric peristalsis causes prolapse of the loose antral mucosa with consequent elongation and ectasia of the mucosal vessels (Fig. 36-11).⁷³ GAVE also has been thought to result from delayed gastric emptying, as well as from humoral factors such as hypergastrinemia, prostaglandin E₂, 5-hydroxytryptamine (serotonin) produced by neuroendocrine cells, and vasoactive intestinal polypeptide (VIP).

Figure 36-11. Endoscopic appearance of watermelon stomach, also referred to as gastric antral vascular ectasia (GAVE).

GAVE is seen particularly in middle-aged or older women and in association with achlorhydria, atrophic gastritis, cirrhosis, and the CREST syndrome, as well as after bone marrow transplantation.^71,74 The association with cirrhosis and portal hypertension in approximately 40% of reported cases of GAVE suggests that this lesion may be caused by portal hypertension or hepatic veno-occlusive disease.⁷⁵ Microscopic features of GAVE include dilated capillaries with focal thrombosis, dilated and tortuous submucosal venous channels, and fibromuscular hyperplasia of the muscularis mucosa.

Some researchers believe that GAVE and portal hypertensive gastropathy (PHG) are different manifestations of the same pathogenetic process, whereas others view them as separate entities with distinct clinical and histologic features. Recent evidence suggests that these are distinct entities.⁷⁶ The pathophysiology of GAVE does not appear to involve portal hypertension because it does not respond to therapies directed at reducing portal pressure. Given case reports of GAVE resolution after liver transplantation, however, it is possible that liver insufficiency may play a role in its pathophysiology.^77,78

PHG is characterized endoscopically by three patterns: (1) fine red speckling of the mucosa; (2) superficial reddening, especially on the tips of the gastric rugae; and, most commonly, (3) the presence of a mosaic pattern with red spots (snakeskin appearance) in the gastric fundus or body (Fig. 36-12). Histologically, the stomach in PHG contains dilated, tortuous, irregular veins in the mucosa and submucosa, sometimes with intimal thickening, usually in the absence of significant inflammation.⁷⁶

Figure 36-12. Portal hypertensive gastropathy. A, Mild disease is manifested by prominence of the areae gastricae, with areas of erythema and subepithelial hemorrhage. This appearance is not pathognomonic and may be noted with other disorders that induce mucosal edema, such as Helicobacter pylori gastritis. B, Severe gastropathy with diffuse subepithelial hemorrhage in a snakeskin pattern. C, Low power photomicrograph showing prominent edema of the lamina propria with multiple congested blood vessels. No histologic evidence of gastritis is seen.

(From Wilcox CM. Atlas of Clinical Gastrointestinal Endoscopy. Philadelphia, Pa: WB Saunders; 1995. p 109.)

Limited therapeutic options are available for treating GAVE. Estrogen-progesterone has been tried⁷⁹ and appears to have some efficacy. Successful use of tranexamic acid, an antifibrinolytic agent,^80,81 and thalidomide⁸² also have been reported. Transjugular intrahepatic portosystemic shunting (TIPS) does not appear to be effective for GAVE.⁸³ This is not surprising given that the pathophysiology of GAVE may not be related to portal hypertension.^78,84 Antrectomy has been used for patients in whom pharmacologic and endoscopic therapies have failed.⁸⁵ Portal hypertension in a patient with GAVE and GI bleeding makes the bleeding more difficult to manage; bleeding is usually greater and more resistant to treatment in the presence of portal hypertension.⁸⁶ Several case reports have detailed reversal of GAVE after liver transplantation,⁷⁷ however, the data are insufficient to recommend this therapy unless the patient is otherwise a liver transplant candidate.

Iron therapy and blood transfusions were the mainstays of medical treatment for GAVE, and antrectomy often was required in severe cases before development of transendoscopic thermal ablation techniques. All of the available endoscopic therapies have been used successfully to ablate GAVE, and now antrectomy is rarely required.⁸⁷ TIPS offers another modality when GAVE is associated with portal hypertension or when bleeding resulting from PHG is not controlled by transendoscopic coagulation therapy (see also Chapters 19 and 90).

The initial management of PHG is with iron supplementation and nonselective beta blockers. Propranolol is the nonselective beta blocker that was investigated in the classic randomized controlled trial evaluating the role of beta blockade in preventing recurrent bleeding in severe PHG.⁸⁸ In this study, patients who received propranolol had a significantly lower rebleeding rate at 12 months (35% versus 62%) and at 30 months (48% versus 93%) compared with patients taking a placebo. If a patient is refractory to beta blocker therapy, however, shunt therapy (TIPS or shunt surgery) is indicated. TIPS placement or shunt surgery has been effective in almost all cases.^83,89–92 The choice between TIPS or surgery should be made based on local expertise.

Somatostain analogs such as octreotide, which are established as effective treatment for acute variceal bleeding, also have been shown to be effective for bleeding from PHG. In two studies evaluating the effect of these vasoactive drugs in acute hemorrhage from PHG,^93,94 bleeding was successfully treated in all patients who received somatostatin or octreotide. Vasopressin and its analog, terlipressin, also have been tried, but results have been mixed.^93,95

PORTAL COLOPATHY AND ENTEROPATHY

Portal colopathy is the term used to describe vascular manifestations of portal hypertension in the colon. Manifestations include hemorrhoids, varices, and spider-like telangiectasias (Fig. 36-13A and B). Mucosal lesions of portal colopathy typically resemble those seen in PHG and may have a diffuse, colitis-like appearance, including granularity, erythema, telangiectases, and friability. Varices and spider-like telangiectases also may be seen in the small intestine, warranting the term portal enteropathy. Histologic changes of portal colopathy and enteropathy are similar to those of portal gastropathy.⁹⁶ The lesions of portal colopathy and enteropathy are amenable to the same thermal therapies used for GAVE and PHG.⁹⁷

Figure 36-13. Endoscopic images showing two examples of portal colopathy. A, A solitary lesion that resembles a spider-like telangiectasia or angioectasia is seen in the rectosigmoid. B, Patchy foci of erythema in the descending colon of a patient with cirrhosis and portal hypertension.

DIEULAFOY’S LESION

This vascular lesion is an unusual cause of massive GI hemorrhage, usually from the stomach, but sometimes from the small or large bowel (Fig. 36-14).⁹⁸ It is twice as common in men as in women and presents at a mean age of 52 years. The vascular abnormality is the presence of arteries of persistently large caliber in the submucosa and, in some instances, the mucosa, typically with a small, overlying mucosal defect. Dieulafoy called the lesion “exulceratio simplex” because he thought it was the initial stage of a gastric ulcer. This lesion also has been called an atherosclerotic aneurysm, an inaccurate term because the caliber of the artery’s walls is uniform throughout and shows no unusual degree of arteriosclerosis. It is believed that focal pressure from these large “caliber-persistent” vessels thins the overlying mucosa, leading to erosion of the exposed vascular wall and resulting hemorrhage. Massive hematemesis or melena typically is not preceded by any GI tract symptoms and usually is followed by intermittent and severe bleeding over several days. The most common site of bleeding is 6 cm distal to the cardioesophageal junction, where the arteries are largest, but many lesions have been reported in extragastric locations, including the esophagus, small bowel, rectum,⁹⁸ and even outside the GI tract in the bronchus, presenting as hemoptysis. It may be difficult to find a Dieulafoy lesion in a patient with upper GI bleeding because the overlying mucosal defect may be small and hidden between the gastric rugae, and the caliber-persistent vessel may constrict and retract after the bleeding episode.

Figure 36-14. Endoscopic images of a Dieulafoy’s lesion. A, Arterial bleeding (spurting) just distal to the gastroesophageal junction. B, The bleeding point was a small defect without endoscopic evidence of ulceration.

(From Wilcox CM. Atlas of Clinical Gastrointestinal Endoscopy. Philadelphia, Pa: WB Saunders; 1995. p 122.)

The mortality rate for older adult patients with this lesion has been high, nearly 80% before diagnostic endoscopy was available and more than 20% in cases reported between 1970 and 1986. The high mortality rate resulted from the inability to localize the bleeding site and the frequent need for emergency gastric surgery. Current angiographic and endoscopic techniques used to localize and treat bleeding lesions have led to an improvement in 30-day mortality rates, now reported to be 13%. Therapeutic approaches to bleeding Dieulafoy’s lesions include injection therapy, heater probe, laser, APC, band ligation, and hemoclip placement.⁹⁹

HEMANGIOMAS

Considered by some to be true neoplasms, hemangiomas generally are thought to be hamartomas because most are present at birth. Hemangiomas are the second most common vascular lesion of the colon and may occur as solitary or multiple lesions limited to the colon or part of diffuse GI or multisystem angiomatoses. Hemangiomas may be classified as cavernous, capillary, or mixed types. Most are small, ranging from a few millimeters to 2 cm, but larger lesions occur, especially in the rectum.

Bleeding from colonic hemangiomas usually is slow, producing occult blood loss with anemia or melena. Hematochezia is less common, except with large cavernous hemangiomas of the rectum, which may cause massive hemorrhage. The diagnosis is best established by endoscopy, including enteroscopy because roentgen studies, including angiography, frequently are normal. The diagnosis of cavernous hemangioma of the rectum often can be suggested on plain films of the abdomen by the presence of phleboliths and displacement or distortion of the rectal air column (Fig. 36-15). On barium enema, the affected rectal lumen typically shows narrowing and rigidity, scalloping of the rectal wall, and widening of the presacral space (see Fig. 36-15). Endoscopically, one sees elevated plum-red nodules or vascular congestion; ulcers and proctitis also may be present. Angiography can demonstrate these lesions but seldom is necessary to establish the diagnosis.

Figure 36-15. Two examples of cavernous hemangioma of the rectum. A, Plain film of the pelvis reveals a soft tissue mass with foci of calcification in abnormal vascular channels. This appearance of pelvic phleboliths in a child is pathognomonic for a cavernous hemangioma. B, A barium enema film shows the characteristic phlebolith pattern outside the colon, with scalloping of the bowel lumen caused by pressure from the vascular lesion.

Hemangiomas are well circumscribed but not encapsulated. Grossly, cavernous hemangiomas appear as polypoid or mound-like reddish purple lesions on the mucosa. Histologically, numerous dilated, irregular blood-filled spaces are seen within the mucosa and submucosa and sometimes extend through the muscular wall to the serosal surface. The vascular channels are lined by flat endothelial cells with flat or plump nuclei, and their walls are composed of fibrous tissue. Capillary hemangiomas are plaque-like or mound-like reddish purple lesions composed of a proliferation of fine, closely packed, newly formed capillaries separated by little stroma. The endothelial cells are large, usually hypertrophic, and in some areas may form solid cords or nodules with ill-defined capillary spaces.

Small hemangiomas that are solitary or few in number and can be approached endoscopically are locally ablated. Most large or multiple lesions require resection of either the hemangioma alone or the involved segment of colon. Local measures to control massive bleeding from cavernous hemangioma of the rectum usually are effective only temporarily. Embolization and surgical ligation of major feeding vessels also have been used, but ultimately excision of the rectum often is required.¹⁰⁰

In a particular entity known as diffuse intestinal hemangiomatosis, numerous lesions, usually of the cavernous type, involve the stomach, small bowel, and colon; hemangiomas of the skin or soft tissues of the head and neck frequently are present. The occurrence of bleeding or anemia in childhood typically leads to the diagnosis, which usually is made after various studies including endoscopy, barium series, scintigraphy with ^99mTc-labeled red blood cells,¹⁰¹ and contrast-enhanced CT. Angiographic findings can be normal despite the number of lesions. Surgical intervention may be required for continuous, slow bleeding or for intussusception. At operation, all identifiable lesions should be excised either through enterotomies or by limited bowel resections. Intraoperative endoscopy may be helpful in finding small lesions. Repeated operations may be necessary to control blood loss.¹⁰² Semaxanib, a small-molecule inhibitor of VEGF receptor 2, recently has been used for treatment of hemangioblastoma in patients with von Hippel-Lindau disease (vHLD). In vHLD, a loss of von Hippel-Lindau protein results in an accumulation of hypoxia-inducible factor and subsequently, excessive production of VEGF.¹⁰³ Recent studies have reported regression or stabilization, with improvement of macular edema, in patients with hemangioblastoma treated with semaxanib, which suggests inhibition of VEGF^103,104 and a role for VEGF inhibitors in the management of hemangiomas.

BLUE RUBBER BLEB NEVUS SYNDROME

In 1860, an association among cutaneous vascular nevi, intestinal lesions, and GI bleeding was described, and almost a century later this constellation of findings was named blue rubber bleb syndrome by Bean to distinguish it from other cutaneous vascular lesions (Fig. 36-16). Although the GI tract is most frequently involved, other sites may be affected, including the eyes, nasopharynx, parotid glands, lungs, liver, spleen, heart, brain, skeletal muscles, urinary bladder, and penis. Orthopedic abnormalities may be present, and calcification, thrombosis, and consumptive coagulopathy (with thrombocytopenia) may occur within the lesions.¹⁰⁵ A familial history is infrequent, although a few cases of autosomal dominant transmission have been reported¹⁰⁶ and one analysis has identified a responsible locus on chromosome 9.

Figure 36-16. Fingertip lesion in a patient with the blue rubber bleb nevus syndrome.

The lesions are distinctive: they are blue and raised, vary from 0.1 to 5 cm in diameter, and have a wrinkled surface. Characteristically, the contained blood can be emptied by direct pressure, leaving a wrinkled sac. Lesions may be single or numerous and are usually found on the trunk, extremities, and face. They may involve any portion of the GI tract but are most common in the small bowel. In the colon they are more common distally. They are detected infrequently by barium or angiographic studies and are seen best by endoscopy. Originally the lesions were thought to be hemangiomas, but they are now considered to be venous malformations. Resection of the involved segment of bowel is recommended for recurrent hemorrhage. Endoscopic laser coagulation may be dangerous because these lesions may involve the full thickness of the bowel wall; successful sclerotherapy and band ligation of GI tract lesions have been reported.

CONGENITAL ARTERIOVENOUS MALFORMATIONS

Arteriovenous malformations (AVMs) are embryonic growth defects and are considered to be developmental anomalies. Although AVMs are found mainly in the extremities, they may occur anywhere in the vascular tree. In the colon they may be small and resemble AEs or they may involve a long segment of bowel. The most extensive lesions typically are in the rectum and sigmoid. Histologically, AVMs are persistent congenital communications between arteries and veins located primarily in the submucosa. Characteristically, there is “arterialization” of the veins (i.e., tortuosity, dilatation, and thick walls with smooth muscle hypertrophy and intimal thickening or sclerosis). In long-standing AVMs, the arteries are dilated with atrophic and sclerotic degeneration. Angiography is the primary means of diagnosis (Fig. 36-17). Early-filling veins in small lesions and extensive dilatation of arteries or veins in large lesions are typical. Patients with significant bleeding from large AVMs should undergo resection of the involved segment; transendoscopic therapy may be beneficial for smaller lesions.

Figure 36-17. Mesenteric angiogram in a patient who presented with recurrent lower intestinal bleeding. The angiogram shows a complex, racemose configuration of vessels in a large congenital arteriovenous malformation involving the superior and inferior mesenteric arterial circulations.

KLIPPEL-TRENAUNAY AND PARKES WEBER SYNDROMES

In its initial description, the Klippel-Trenaunay syndrome consisted of (1) a vascular nevus involving the lower limb; (2) varicose veins limited to the affected side and appearing at birth or in childhood; and (3) hypertrophy of all tissues of the involved limb, especially the bones.¹⁰⁷ Subsequently, a variety of vascular lesions associated with the hypertrophic limb were described and some authors now divide the syndrome into two: Klippel-Trenaunay and Parkes Weber; the former is a pure low-flow condition, whereas the latter is characterized by arteriovenous fistulas. Several genetic defects in the regulation of the angiogenic factor VG5Q have been shown in patients with this syndrome.¹⁰⁸ The cause of bony elongation is controversial, but one theory invokes in utero venous hypertension and stasis.¹⁰⁷ Edema of the involved leg is common, and if the thigh is involved, a variety of lymphatic abnormalities are usually present (e.g., chylous mesenteric cysts, chyloperitoneum, protein-losing enteropathy; see Chapters 28 and 37).

Symptomatic GI involvement is rare. In the largest series, the most common GI symptom was hematochezia, reported by only 6 of 588 patients.¹⁰⁷ GI bleeding may be recurrent and mild or severe and usually is caused by a rectal hemangioma, localized rectovaginal varices resulting from obstruction of the internal iliac system, or portal hypertension with varices. Bleeding may be intensified by consumption coagulopathy, which may occur within the smaller sinusoids of the vascular lesion. Physical examination is diagnostic, and various imaging techniques are used to define the anatomy and plan surgical repair.¹⁰⁹ Most recently, MRA has been used for diagnosis and to detect arteriovenous shunting.¹¹⁰ Endoscopic thermal ablation therapy is useful in controlling hemorrhage and preventing or minimizing recurrent GI bleeding, especially when the lesions are relatively well localized (L. Brandt, personal experience).

ABDOMINAL AORTIC ANEURYSM

Approximately 95% of abdominal aortic aneurysms (AAAs) are atherosclerotic in origin, but other factors such as genetic predisposition are also important; less common causes include trauma, vasculitis, infection, and congenital abnormalities. Eighty-five percent of affected people are men. Familial clustering of AAAs has been noted in 15% to 20% of cases, and in some families an abnormality has been identified on chromosome 16¹¹¹; defects in procollagen III in patients with Ehlers-Danlos syndrome type IV and altered gene expression causing abnormalities of the elastin and collagen content of aneurysms have been shown in other families.¹¹¹

Most AAAs are asymptomatic. The most common symptom is epigastric pain, often radiating through to the back; severe pain may presage rupture. On physical examination, a pulsatile epigastric mass may be palpable. Distinguishing an aneurysm from an overlying abdominal mass with transmitted pulsations may be difficult on physical examination and is best done by imaging studies. A bruit may be present, but unless recent in onset, it is usually of no diagnostic help.

Abdominal plain films may show a soft tissue mass with peripheral calcification in the region of the abdominal aorta. With large aneurysms, erosion of the lumbar vertebrae or displacement of surrounding viscera, including bowel, kidneys, and ureters, may be seen. Because plain film studies are not sufficiently sensitive to establish the presence or size of an aneurysm, ultrasonography, CT, and MRI have become the standard means of evaluation. These procedures are simple, safe, and accurate in the diagnosis and sizing of aneurysms. Ultrasonography is less sensitive than CT in determining the extent of the aneurysmal process, but it is useful for following changes in the size of the aneurysm.¹¹² CT and MRI are used preoperatively to demonstrate aortic and vascular anatomy. Preoperative angiography is not used as frequently as in the past and is most appropriate in patients with evidence of peripheral vascular disease, severe hypertension, symptoms of chronic mesenteric ischemia (see Chapter 114), if thoracic or iliac artery involvement is suspected and, in cases of horseshoe or pelvic kidneys, to demonstrate renal artery anatomy. Angiography is not used to estimate the size of the aneurysm because intraluminal laminated thrombus limits delineation of the entire lumen.

The major complication of AAAs is rupture, which is heralded by the sudden onset or worsening of pain in the abdomen, flank, or back; pain may be present for several weeks and is attributable to “leakage” that precedes overt rupture. Pain may be exacerbated by lying recumbent and relieved by sitting or leaning forward. In one series, only 14% of patients referred for treatment of rupture had been known to have an aneurysm previously.¹¹³ Severe abdominal pain also may be seen with aortic dissection as the splanchnic vessels become compromised and acute intestinal ischemia develops. The consensus among vascular surgeons is that the most important predictor of rupture is the size of the aneurysm. The risk of rupture for small aneurysms is negligible and in one series was reported to be 0% at five years¹¹⁴; the five-year risk for aneurysms that are 5.5 to 5.9 cm in size is about 20% to 25%; for a 6-cm aneurysm, the risk is 35% to 40%; and for those larger than 7 cm, the risk is 75%.¹¹¹ Other risk factors for rupture include hypertension and the presence of chronic obstructive pulmonary disease. AAAs most commonly rupture into the retroperitoneal tissues that surround the aorta. Less commonly, the aneurysm may communicate with the peritoneal cavity, in which case shock develops rapidly. Patients whose aneurysm ruptures into the small intestine, usually the third or fourth portions of the duodenum, typically present with massive GI bleeding; bleeding may be intermittent because a clot alternately forms and is dislodged from the eroded bowel or fistulous opening. Indeed, many of these patients will have a “herald bleed” followed by massive hemorrhage several hours or days later.¹¹⁵ Endoscopy is the most sensitive method for diagnosing this complication. Rarely, abdominal aneurysms rupture into the inferior vena cava; if so, a loud bruit can be heard.

Operative management of an AAA usually consists of replacement of the aneurysm with a prosthetic graft, which may be done via laparotomy through a retroperitoneal or groin incision and use of an endovascular graft. In elective cases, preoperative angiography is useful for demonstrating additional vascular disease (e.g., stenosis or occlusion of the splanchnic arteries) and, by allowing planned vascular reconstruction, may help avoid postoperative bowel ischemia. The mortality of aneurysm repair in good-risk patients is 1% to 4%¹¹⁵; mortality increases sharply to 34% to 85% when surgery is done as an emergency for rupture or impending rupture.^113,116,117 Increasingly, endovascular aneurysm repair (EVAR) is being used as an alternative to open repair of an AAA. Recent studies have shown that both can be performed safely in patients treated for elective infrarenal AAAs. EVAR has the perioperative advantages of reduced blood loss, and reduced length of intensive care unit and hospital stay^118,119; however, concerns have been raised about endovascular leaks and late rupture.^115,120

Aneurysms larger than 5 cm, symptomatic aneurysms, or enlarging aneurysms of any size should be treated electively in good-risk patients. Patients who cannot tolerate an open operation may sometimes still be treated with an endovascular graft.^120–122 Patients with asymptomatic and nonexpanding aneurysms that are 4 to 5 cm in diameter are best treated conservatively because rupture of such small AAAs is rare. Aneurysms that are not treated surgically should be followed by ultrasound every three to six months. The growth rate of AAAs is variable and has been less in recent studies than in older ones. Study of the growth rate of small aneurysms (average initial size of 4 cm) in a large population of well-studied patients revealed that over an average of 3.3 years, 58.4% of patients had no change or a decrease in aneurysm size, 25.3% had an expansion between 0.1 and 0.25 cm, 12.6 had an increase of greater than 0.25 cm, and only 3.7% had an enlargement of more than 0.5 cm.¹¹¹ On average, the growth rate of an AAA is 0.35 cm per year.

MYCOTIC ANEURYSMS

Mycotic aneurysms of the aorta and splanchnic vessels are rare. They were so-named by Sir William Osler because their appearance reminded him of fungi (mykes, fungus). In the past, mycotic aneurysms were most commonly caused by septic emboli from bacterial endocarditis. Today the main risk factor is intravenous drug use. Other important risk factors include contiguous spread from adjacent infectious processes, arterial manipulation, and immunocompromise (e.g., alcoholism, diabetes mellitus, chemotherapy, and treatment with glucocorticoids). Salmonella (especially Salmonella choleraesuis) and Staphylococcus are the most common infecting organisms. The celiac artery (CA) is most often affected, followed by the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). Early in the course, symptoms of mycotic aneurysms are nonspecific. Later, fever, chills, and abdominal pain are typical. Diagnosis is by imaging the vasculature: mycotic aneurysms typically are lobulated and saccular and affect the upper abdominal aorta (Fig. 36-18). The destructive process can develop quickly, leading to rapid expansion and rupture. Treatment is surgical, usually with resection of the aneurysm and vascular reconstruction.¹²³

Figure 36-18. Spiral computed tomographic scan of the abdomen revealing an irregular pseudoaneurysm arising from a calcified left common iliac artery. Contrast material is seen in the clot and extends outside the wall of the vessel and into the adjacent bowel.

(Courtesy Dr. Alla Rozenblitt, Bronx, New York.)

PARAPROSTHETIC ENTERIC AND AORTOENTERIC FISTULAS

An uncommon but potentially catastrophic complication of aortic aneurysmectomy and other procedures in which vascular prostheses are placed in the retroperitoneum or abdomen is the formation of a fistula between the graft and the adjacent bowel, usually the third or fourth portion of the duodenum (Fig. 36-19).^124,125 The frequency of this complication is between 0.6% and 2.35%. Such fistulas develop as early as 21 days postoperatively, but in most cases, they are delayed beyond two years; in one case, an interval of 14 years was documented. This complication is thought to result from local conditions at the time of, or subsequent to, graft placement, including infection, damage to the duodenum or its blood supply during the dissection, and subsequent erosion of the duodenal wall by the graft. Newer surgical techniques, including the use of nonabsorbable sutures and antibiotics, strict hemostasis, and covering of suture lines with retroperitoneal tissue and peritoneum, as well as the increasing use of endovascular grafts, may reduce the frequency of fistula formation.

Figure 36-19. Endoscopic view of the third portion of the duodenum, where part of an aortic graft is seen. Patients with aortic graft-enteric fistulas typically present with gastrointestinal bleeding, abdominal pain, and fever because the graft usually has become infected by the time it erodes into the gastrointestinal tract.

Patients with aortoenteric fistulas present with upper or lower GI bleeding that if untreated may be massive and rapidly fatal. Upper GI endoscopy is the procedure of choice for aiding diagnosis by excluding other obvious lesions, but CT imaging is helpful.¹²⁶ The most important clue to the diagnosis is awareness of the possibility in a patient with GI bleeding who has had an aortoiliac artery graft. Prompt diagnosis and expedient surgical repair are essential for survival.

SUPERIOR MESENTERIC ARTERY SYNDROME

The third portion of the duodenum is cradled in an angle of about 45 degrees formed by the root of the SMA and the wall of the aorta. When this angle is narrowed to less than 25 degrees, the SMA impinges on the duodenum, thereby leading to gastric and intestinal obstruction, a condition referred to as Wilkie’s syndrome or the superior mesenteric artery syndrome (Fig. 36-20).^127,128 The latter term may be confusing because the condition is not one of vascular insufficiency. Symptoms may be acute or chronic and typically include epigastric pain, vomiting, and early satiety. The syndrome has been associated with immobilization in a body cast; rapid growth in children; and marked, rapid weight loss in adults, particularly young women with an eating disorder (see Chapter 8). Rarely, anatomic anomalies predispose to the condition, including a high ligament of Treitz or low origin of the SMA.

Figure 36-20. Film from an apper gastrointestinal and small bowel follow-through in a patient with superior mesenteric artery syndrome. The patient had symptoms compatible with gastric outlet obstruction, and on this film the second and third portions of the duodenum are markedly dilated.

(Courtesy Dr. Ellen Wolf, Bronx, New York.)

Barium studies may show an abrupt cutoff in the third portion of the duodenum with dilatation proximally, particularly when the patient is supine. Treatment approaches have included small feedings or a liquid diet. Modern imaging techniques such as CTA and MRA can provide noninvasive and detailed anatomic information that can be used in diagnosing the condition and planning surgical approaches.^129,130 Symptoms typically improve after restoration of lost weight or removal of a body cast. Surgery is necessary only rarely. Duodenojejunostomy may relieve the symptoms and has been performed for this condition laparoscopically.¹³¹

CELIAC AXIS COMPRESSION SYNDROME

Whether celiac axis compression syndrome (CACS) is a cause of GI ischemia has been a subject of controversy ever since the description of postprandial pain and an epigastric bruit in a patient in whom angiography showed narrowing of the CA caused by compression of a fibrotic celiac ganglion.¹³² After release of the artery, the murmur and postprandial pain disappeared. Since that description, compression of the CA by the median arcuate ligament of the diaphragm and the celiac ganglion has been identified but is not well understood.

A major difficulty in determining the validity of CACS as an entity, also sometimes referred to as Dunbar syndrome, arises from the different criteria used by various investigators to define it.^133,134 At the least, clinical features that should be present to diagnose CACS include postprandial epigastric pain, diarrhea, weight loss, and an abdominal bruit that intensifies with expiration.

Compression of the CA is demonstrated by lateral aortography or selective studies of the CA. Endoscopic ultrasound, CTA, and MRA are noninvasive means of demonstrating the anatomy and compression of the CA.¹³⁵ Compression by the crural fibers of the diaphragm or the celiac ganglion produces a smooth, asymmetrical narrowing of the superior aspect of the celiac axis and displaces it toward the SMA (Fig. 36-21). These findings are shown best during expiration.

Figure 36-21. Film from a lateral flush aortogram showing typical compression of the origin of the celiac axis with some poststenotic dilatation. The study is from a patient with no gastrointestinal complaints related to this finding.

(From Boley SJ, Brandt LJ, Veith FJ. Ischemic disorders of the intestines. Curr Probl Surg 1978; 15:1.)

The clinical significance of narrowing of the CA on angiography has been questioned because it occurs with equal frequency in patients in whom intestinal angina is suspected, in those with GI diseases not primarily characterized by pain, and in those with miscellaneous problems that do not involve the alimentary tract. Because the anatomic lesion that forms the basis for the syndrome is narrowing of the major artery to the upper abdominal viscera, the pain most frequently has been attributed to ischemia. This concept has persisted, despite clinical and experimental evidence that isolated compromise of the CA is almost always compensated by collateral circulation from either the SMA or the IMA.

A popular alternative theory to the ischemic origin of the pain in CACS is that the pain arises in the celiac ganglion itself, possibly secondary to pressure or throbbing by the compressed artery. The increased splanchnic blood flow and dilation of the artery that accompany the ingestion of food may explain the relationship of pain to meals.

Operative approaches to CACS include division of the median arcuate ligament, with or without gangliectomy, or arterial reconstruction or bypass. Laparoscopy has been successful in releasing the compression.¹³⁵ Results of operations for CACS have varied as much as have the criteria used to diagnose them. In the largest study of the long-term results of patients treated for CACS, Evans found that 83% of patients were asymptomatic 6 months after a decompression procedure, but only 41% remained asymptomatic 3 to 11 years later.¹³⁶ Furthermore, no correlation existed between the presenting symptoms and the results of surgery and no clinical patterns emerged to identify those patients who might benefit from surgery. Additionally, of 12 patients treated nonoperatively, 9 remained free of pain at the time of Evans’s report.

The controversy concerning CACS continues. A small number of patients who have otherwise unexplained abdominal pain not helped by standard regimens are relieved by some aspect of the operations performed for celiac axis compression.¹³⁷ If surgery is performed only in patients who fulfill the criteria previously described, unnecessary procedures should be kept to a minimum.