Specific Etiologies and Treatments

The small bowel is an unusual but important source of GI blood loss. In patients with negative repeat endoscopy and colonoscopy, the small bowel should become the focus of further investigation. The overwhelming majority of small bowel bleeding originates from vascular lesions (ie, arteriovenous malformations [AVM]) and small bowel tumors. Other less common sources include drug-induced ulcerations, Crohn's disease (CD), Dieulafoy's malformation, and metastatic tumors to the small bowel. The likely bleeding source varies depending on the age of the affected individual (Table 59-4).

OGIB in patients 40 years of age and younger is more likely caused by small bowel tumors (primary and metastatic), CD, Meckel's diverticulum, and vascular malformations. Whereas patients older than 40 years of age with comorbidities, tend to have more AVMs, Dieulafoy's disease, and small bowel ulcerations secondary to NSAID use. Specific management strategies, depending on etiology, are discussed below.

Intestinal Angioectasias

The etiology of AVMs is not known but there is clear association with specific clinical conditions such as valvular heart disease, chronic liver/renal disease, collagen vascular disorders, intestinal radiation, vWD, and hereditary disorders like OWR. Most AVMs remain clinically asymptomatic; therefore, their prevalence is difficult to estimate. Unless specifically identified as the cause of bleeding they should not be treated. Bleeding is typically painless, and may be chronic, subacute, or, in approximately 15% of patients, acute and massive. Treatment is directed at both the underlying condition and the AVM itself. When diagnosed as the likely cause of bleeding, endoscopic therapy seems like a reasonable approach. However, the visualized AVMs may be indicative of others located distally, which can be the source of ongoing bleeding. Endoscopic therapy with electrocoagulation may be only temporizing and repeat endoscopic sessions at regular intervals may be necessary. Thermal contact, which can be applied effectively with heater probe, bipolar electrocoagulation (BICAP) and argon plasma coagulation (APC), are generally available and easy to use. Conversely, injection sclerotherapy is

TABLE 59-4. Obscure Gastrointestinal Bleeding Etiology Depending On Age

Age 40 Years or Younger

Small bowel tumors Crohn's disease Meckel's diverticulum Small bowel tumors Polyposis syndromes AVM

Dieulafoy's malformation von Willebrand's disease Drug-induced small bowel injury Portal hypertensive intestinal "opathy" Pancreatic hemosuccus

Older Than Age 40 Years

AVM GAVE

Cameron's ulcer

Drug-induced small bowel injury Dieulafoy's malformation Amyloidosis von Willebrand's disease Portal hypertensive intestinal "opathy" Pancreatic hemosuccus Osler-Weber-Rendu

Adapted from Mujica and Barkin, 1996. AVM = arteriovenous malformations; GAVE = gastric antral vascular ectasias.

rather ineffective. Hemostasis can be achieved in 50 to 85% of the lesions regardless of which contact endoscopic technique is used (Van Cutsem and Piessevaux, 1996). In patients with large and multiple AVMs, such as those with OWR, coaptation in a centripetal pattern with BICAP or APC is preferred to obliterate the AVM. Control of bleeding may be difficult. Massive or recurrent, severe bleeding may warrant angiographic and/or surgical intervention with enterotomy and resection.

Small Bowel Tumors

Neoplasms of the small intestine are uncommon and often remain clinically unrecognized. Bleeding occurs in 25 to 50% of patients with small bowel tumors (Bashir and Al-Kawas, 1996) and comprises approximately 5 to 10% of cases of bleeding of obscure origin. Benign tumors are more likely to bleed than malignant lesions. When recognized, most will warrant endoscopic resection or, when not amenable to endoscopic resection, surgical evaluation and resection. Benign small bowel lesions include adenomas, leiomyomas, lipomas, hamartomas, and rarely neural tumors. Occasionally, pain or obstructive-type symptoms may lead to their diagnosis. Although a pattern of obscure-occult bleeding is more characteristic of benign small bowel tumors, lesions in the duodenum may present with frank hematemesis and those in the ileum with hematochezia. Adenomas are usually found proximal to the ligament of Treitz and account for 25% of benign lesions. All adenomas in the small bowel should be viewed as premalignant lesions

TABLE 59-5. Causes of Small Bowel Ulceration

Drugs NSAIDs Potassium Salicylates Neoplasms Adenocarcinoma Lymphoma Melanoma Infections CMV

Tuberculosis Syphilis Yersinia Campylobacter Inflammatory Diseases Crohn's disease Celiac disease Behget's syndrome Ulcerative jejunoileitis Vasculitis Radiation enteritis

Adapted from Bashir and Al-Kawas, 1996.

CMV = cytomegalovirus; NSAID = nonsteroidal anti-inflammatory drug.

and removed regardless of bleeding. Duodenoscopy with a side viewing endoscope may be necessary for diagnosis and treatment of periampullary adenomas such as those seen in familial adenomatous polyposis (FAP). Leiomyomas are the second most common tumor of the small intestine and are also the most likely small bowel tumors to bleed. They are composed primarily of smooth muscle cells and as they enlarge, tumor necrosis results in a central umbilication and ulceration that predisposes to bleeding. If they become large, small bowel series may reveal an intraluminal mass. These are very vascular tumors and 86% will demonstrate a tumor blush on angiography (Cho and Reuter, 1980). Surgical resection is mandatory for large lesions as they are grossly indistinguishable from leiomyosarcomas. Lipomas rarely bleed and, in general, require no specific treatment. When larger than 4 cm, superficial ulceration may occur that can be treated locally with injection therapy or thermal coagulation.

Small bowel malignancies are rare, accounting for < 2% of all GI cancers. Primary small bowel lesions include adenocarcinomas, carcinoid tumors, lymphoma, and leiomyosarcomas. Metastatic lesions may arise from melanoma, Kaposi's sarcoma, lung, breast, and renal cell carcinoma. They are more commonly seen in patients in their fifth to seventh decade of life. Adenocarcinomas are the most common small bowel malignant tumors to cause intestinal bleeding with an incidence approaching 60% (Bashir and Al-Kawas, 1996). In the setting of CD, adenocarcinomas tend to occur distally and are more common in the small bowel than the colon. Endoscopic treatment of small bowel malignancies is highly unsuccessful and associated with the occurrence of a high rate of complications; therefore, treatment with surgical resection, if possible, is preferred.

Miscellaneous

Ulcers distal to the ligament of Treitz are rare causes of GI bleeding and are difficult to diagnose. Their multiple causes and associated conditions are reflected in Table 59-6. Recently, capsule endoscopy has shown that 58% of NSAID users develop small bowel lesions as compared to 17% of nonusers(Graham et al, 2003). Risk factors are likely similar to those for more proximal ulceration and include duration of use, age over 60 years, associated comorbidities, concurrent steroid use, and use of multiple NSAIDs, alcohol, and tobacco. Interestingly, Goldstein and colleagues confirmed that approximately 14% of healthy volunteers also have lesions (petechiae, erosions, and mucosal breaks) on capsule endoscopy (Goldstein et al, 2003) reminding us that visualized pathology may not necessarily constitute a definitive diagnosis.

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