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Chronic gastrointestinal (GI) hemorrhage may be overt or occult. Overt bleeding is defined as chronic if it is persistent but not severe enough to cause circulatory compromise. It may be seen in the form of melena or red rectal bleeding. If bleeding is occult, patients may present with symptomatic anemia and evidence of occult bleeding with stool testing. In some patients, chronic hemorrhage may be clinically interspersed with acute episodes. Acute GI bleeding is discussed in detail in Chapters 14 – 17 .
Chronic GI bleeding includes common clinical scenarios, yet the meaning and diagnostic criteria for the different terms are not well delineated. Chronic bleeding from the gut is always significant; in particular, malignant tumors of the gut that are curable may be present. There is no universal agreement regarding the nomenclature of GI lesions that can cause chronic bleeding. Development of new technology, mainly wireless video capsule endoscopy (CE) and balloon-assisted enteroscopy, has provided an opportunity to revisit the traditional classifications of the source of GI bleeding into upper or lower GI bleeding based on the location of the bleeding, either proximal or distal to the ligament of Treitz.
Some authors propose reclassifying GI bleeding into three categories: upper GI, mid-GI, and lower GI bleeding. Bleeding above the ampulla of Vater, within the reach of esophagogastroduodenoscopy (EGD), is defined as upper GI bleeding; small intestinal bleeding from the ampulla of Vater to the terminal ileum, best investigated by CE and balloon-assisted enteroscopy, is defined as mid-GI bleeding; and colonic bleeding, which can be evaluated by colonoscopy, is defined as lower GI bleeding. A simple classification is presented in Table 18.1 . This chapter discusses the evaluation and some of the most frequent causes of occult or unexplained chronic GI bleeding.
Gastrointestinal Lesions | |
Within Reach of Upper Endoscope | May Be Beyond Reach of Upper Endoscope |
Esophagitis | Celiac sprue |
Cameron lesions | Crohn's disease |
Peptic ulcer disease | Intestinal lymphoma |
Gastritis and erosions | Small bowel angiodysplasia |
Duodenitis and erosions | Small bowel tumors |
Angiodysplasia | Small bowel ulcers and erosions, including NSAID- and other drug-induced lesions |
Portal hypertensive gastropathy | Small bowel diverticulosis |
Gastroesophageal cancer | Small bowel varices |
Gastric or duodenal polyps | Lymphangioma |
Gastroduodenal lymphoma | Radiation enteritis |
Partial gastrectomy | Blue rubber bleb nevus syndrome |
GAVE | Osler-Weber-Rendu syndrome |
Dieulafoy's lesion | Small bowel polyposis syndromes |
Gardner's syndrome | |
Amyloidosis | |
Meckel's diverticulum | |
Hemosuccus pancreaticus, hemobilia | |
Klippel-Trénaunay-Weber syndrome | |
Colonic Lesions | |
|
Vascular lesions are a common cause of chronic GI bleeding. Arteriovenous malformations (AVMs) of the small bowel account for 30% to 40% of unexplained chronic GI bleeding and are the most common source in older patients. The categorization of vascular abnormalities in the GI tract has been inconsistent and a source of confusion. It can be based on histologic characteristics, gross appearance, or association with systemic diseases. These considerations permit categorization into three broad groups, as follows:
Vascular tumors , which can be benign (e.g., hemangiomas) or malignant (e.g., Kaposi's sarcoma or angiosarcoma).
Vascular anomalies associated with congenital or systemic diseases, such as blue rubber bleb nevus syndrome, Klippel-Trénaunay-Weber syndrome, Ehlers-Danlos syndrome, pseudoxanthoma elasticum, the CREST ( c alcinosis, R aynaud's phenomenon, e sophageal dysmotility, s cleroderma, and t elangioectasias) variant of scleroderma, and hereditary hemorrhagic telangiectasia.
Acquired or sporadic lesions , such as angiodysplasias, gastric antral vascular ectasia, portal hypertensive enteropathy, radiation-induced vascular ectasias, and Dieulafoy's lesions.
Younger individuals (< 40 years of age) most commonly have chronic unexplained bleeding due to Crohn's disease or Meckel's diverticulum–associated ulceration(s). Small bowel neoplasms (e.g., GI stromal tumor, lymphoma, carcinoid, adenocarcinoma, or other polypoid lesions) and Dieulafoy's lesions can occur in both younger and older patients. Nonsteroidal antiinflammatory drug (NSAID) enteropathy has been associated with mucosal erosions, ulcers, and strictures of the small bowel. Less common causes of unexplained GI bleeding include hemosuccus pancreaticus, Strongyloides stercoralis infection, radiation-induced enteritis, and pseudoxanthoma elasticum.
Patient age, symptoms, medical/surgical history, physical examination findings, and laboratory data may all provide clues and help guide diagnostic investigations. Recurrent hematemesis indicates bleeding proximal to the ligament of Treitz, whereas recurrent passage of hematochezia without hemodynamic instability usually suggests a colonic source. Melena can originate from a bleeding site located anywhere from the upper GI tract to the right colon. Thus, a history of melena provides only limited value in terms of localization of obscure GI bleeding. A thorough review of medications may reveal inadvertent use of NSAIDs. A family history of cancer occurring at an early age, particularly colorectal or endometrial, may suggest the presence of hereditary nonpolyposis colorectal cancer. Skin, nail, and oral mucosal changes may suggest the presence of several disorders associated with obscure GI bleeding or iron deficiency anemia, including telangiectasias, which may reflect hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome); other conditions with cutaneous and GI manifestations include Kaposi's sarcoma, Peutz-Jeghers syndrome, tylosis, pseudoxanthoma elasticum, Ehlers-Danlos syndrome, blue rubber bleb nevus syndrome, Henoch-Schönlein purpura, neurofibromatosis, malignant atrophic papulosis, and Klippel-Trénaunay-Weber syndrome.
Second-look upper endoscopy may be helpful in identifying bleeding lesions potentially overlooked or unrecognized at the time of the initial endoscopic evaluation. Data suggest that 2% to 25% of lesions causing obscure gastrointestinal bleeding may be overlooked and are within reach of a standard upper endoscope. More recent studies using double-balloon enteroscopy (DBE) and CE have also confirmed these findings. Commonly overlooked lesions in the upper GI tract include Cameron's erosions or ulcerations in large hiatal hernias, isolated gastric fundal varices, peptic ulcers, AVMs including gastric antral vascular ectasia (watermelon stomach), and Dieulafoy's lesion. An aorto-enteric fistula should always be considered in patients with prior abdominal aortic aneurysm repair. If second-look upper endoscopy is selected, push enteroscopy may be the chosen method to more thoroughly examine the distal duodenum and proximal jejunum in addition to the more proximal upper GI tract.
Although the reported yield of repeat colonoscopy is low (6%–23%), it may be helpful in selected patients when the original colonoscopy examination was documented to have had a mediocre or poor preparation, the extent of the examination was not to the cecum, the patient is older and risk of a previously missed neoplastic lesion is considered, or the terminal ileum was not previously evaluated. Lesions missed or unrecognized during colonoscopy may include AVMs, polyps, solitary rectal ulcers, rectal varices, and neoplasms.
Vascular ectasia of the GI tract, also referred to as angiodysplasia (AD) or less accurately as AVM, is a distinct clinical and pathologic entity. It is the most common vascular abnormality of the GI tract and probably the most frequent cause of lower intestinal bleeding in patients older than 60 years. Although the terms angiodysplasia and arteriovenous malformation have been used synonymously, the term angiodysplasia (Greek angeion, “vessel”; dys , “bad” or “difficult”; plasis , “a molding”) means a poorly formed vessel but with a lesser connotation of congenital origin than with the word malformation . AD are usually distinguished from telangiectasias, which, although anatomically similar, are usually referred to in the context of systemic or hereditary diseases. Because most vascular abnormalities are detected during endoscopy, a classification based on endoscopic appearance has been proposed. The classification system recognizes the location, size, and number of AD.
AD are composed of ectatic, dilated, thin-walled vessels that are lined by endothelium alone or by only small amounts of smooth muscle. Arteriovenous communications are present because of incompetence of the precapillary sphincter. Enlarged arteries are also present in bigger AD and may be associated with arteriovenous fistulas, which explains why bleeding can be a risk in some patients. Histologic examination shows dilated vessels in the mucosa and submucosa, sometimes covered by a single layer of surface epithelium. The pathogenesis of AD is not well understood. Several theories have been proposed, as follows:
AD may develop in response to chronic partial, intermittent, low-grade obstruction of the submucosal veins at the point where they penetrate the muscle layers of the colon. Following this logic, the prevalence of vascular ectasias in the right colon can be attributed to a greater tension in the cecal wall compared with other parts of the colon, according to LaPlace's principle. Over many years, repeated contraction and distention of the cecum results in dilation and tortuosity of the submucosal vein and, later, the venules and capillaries draining into it. Finally, the capillary rings dilate, the precapillary sphincters become incompetent, and a tiny arteriovenous fistula develops.
AD may be a complication of chronic mucosal ischemia, which can occur during episodes of bowel obstruction or straining stools.
AD may be a complication of local ischemia associated with cardiac, vascular, or pulmonary disease.
AD may be congenital, which is probably more likely in young patients or patients who have angiodysplasias associated with congenital diseases.
Increased expression of angiogenic factors, namely vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, has been demonstrated in human colonic AD and is therefore likely to play a very important role in the development of these lesions as well as in modifying the risk of bleeding.
The prevalence of GI angiodysplasias in the overall population is not well known, but angioectasiases have been seen in 0.2% to 2.9% of “nonbleeding persons” and in 2.6% to 6.2% of patients evaluated specifically for occult blood in the stool, anemia, or hemorrhage. AD occur most often in the colon, where they are an important cause of lower GI bleeding, particularly in patients older than 60 years of age, although presentation in patients in their 30s has been described. There is no gender predilection.
AD can remain clinically silent or cause bleeding. The estimated incidence of active GI bleeding in patients with AD is less than 10%. These lesions may be located throughout the GI tract with a variable rate of bleeding associated with them and presentation ranging from hematemesis or hematochezia to occult anemia. Bleeding is usually chronic or recurrent and, in most cases, low grade and painless.
AD of the stomach have been found to be the cause of blood loss in 4% to 7% of patients with GI bleeding. AD in the stomach or duodenum are found incidentally in approximately 50% of cases. The risk that an incidentally found gastric or duodenal AD will subsequently bleed is uncertain. Patients who have bled from gastric or duodenal AD do rebleed. This rebleeding was illustrated in a series of 30 patients with gastric or duodenal AD; 77% had experienced at least one episode of overt bleeding before diagnosis. Approximately 5% of patients presenting with GI hemorrhage have no source found by upper endoscopy and colonoscopy. In approximately 75% of these patients, responsible lesions can be detected in the small bowel. In patients presenting with obscure overt bleeding (defined as the presence of recurrent melena or hematochezia with normal evaluation by upper endoscopy and colonoscopy), small bowel angioectasias are detected in 30% to 60% of examinations.
The colon is the most common site of AD in the GI tract; colonic lesions are most often found in the cecum and ascending colon. In some reported experiences, AD of the colon account for approximately 20% to 30% of cases of acute lower GI bleeding, approaching the frequency of acute colonic diverticular bleeding. Foutch et al (1995) noted the prevalence of AD to be 0.83% from three prospective studies in which screening colonoscopies were performed in 964 asymptomatic individuals (mean age 61 years) and none of them developed bleeding over a mean follow-up of 3 years.
AD is the second most common cause of GI bleeding in patients with end-stage renal disease. These lesions account for approximately 20% of upper GI bleeds and 30% of lower GI bleeds, and approximately 50% of recurrent upper GI bleeds. In a prospective study of upper GI hemorrhage over a 50-month period, vascular ectasia was the etiology of upper GI hemorrhage in 13% of patients with renal insufficiency and was the etiology of bleeding more often in patients with renal insufficiency than in patients with normal renal function. The prevalence of vascular ectasia as a cause of upper GI bleeding was related to the duration of renal failure and the requirement of hemodialysis. Although the reason for the increased prevalence among patients with end-stage renal disease is unknown, a possible explanation is that there is an increased risk of bleeding associated with uremia-induced platelet dysfunction (aggregation and adhesion).
von Willebrand's disease is a bleeding disorder that results from a qualitative or quantitative defect in von Willebrand factor (vWF). vWF is a complex multimeric glycoprotein present in platelets, plasma, and subendothelium, and is essential to platelet adhesion and aggregation at the site of vascular injury. In a study of patients with both bleeding and nonbleeding angioectasias of the GI tract and control patients with colonic diverticular hemorrhage, Veyradier et al (2001) showed that most patients with bleeding angioectasias of the GI tract lack the largest multimers of vWF induced by a latent acquired form of von Willebrand's disease. Because these specific multimers are the most effective in inducing platelet aggregation in high shear stress that is commonly present in the microcirculation of angioectasias, it was concluded their deficiency contributes to active bleeding.
Approximately 50% of patients with bleeding vascular ectasias have evidence of cardiac disease, and 25% have been reported to have aortic stenosis (AS). Bleeding from angiodysplasias in patients with AS (Heyde's syndrome) has been repeatedly reported but is highly controversial. Support for this hypothesis comes from evidence of improvement or cessation of chronic GI bleeding in the vast majority of patients with AS after aortic valve replacement. This effect was sustained for up to 12 years after surgery in the largest case series of 91 patients.
Two possible explanations have been proposed to explain this observation. Patients with AS may develop an acquired form of von Willebrand's disease, which can be reversed after aortic valve replacement. Patients with AS may be more likely to bleed from existing AD. Another explanation is that existing AD may bleed as a result of ischemic necrosis in patients who have a low cardiac output. However, this explanation is inconsistent with the observations that bleeding AD have not been observed with other forms of heart disease associated with a low cardiac output and that a low cardiac output is a late complication of AS.
Several retrospective, uncontrolled studies and a prospective, controlled investigation do not substantiate a causative role or association of aortic valve diseases with colonic angioectasias. Replacement of the aortic valve for control of bleeding secondary to these vascular lesions is not universally accepted. A logical approach to patients with both lesions is to treat the colonic lesion first endoscopically, regardless of whether the patient's cardiac status warrants surgery. If valve replacement is necessary and endoscopic therapy is unsuccessful, further endoscopic or surgical treatment of the colonic AD should be delayed until after cardiac surgery. Further attempts at endoscopic treatment or surgical resection are indicated if bleeding recurs.
Vascular lesions are a prominent feature of progressive systemic sclerosis, especially in the CREST variant. In patients with progressive systemic sclerosis, sites most frequently affected by telangioectasias are the hands, lips, tongue, and face, but gastric, intestinal, and colorectal lesions have been reported. These lesions may be the source of occult or clinically significant bleeding and are best treated by endoscopic coagulation.
Patients with left ventricular assist devices have higher rates of GI bleeding, most commonly from angioectasias in the upper digestive tract and small bowel.
Angioectasias have a characteristic appearance of a cherry-red, fern-like pattern of arborizing, ectatic blood vessels radiating from a central vessel ( Fig. 18.1 ). This pattern should be specifically looked for because angioectasias may be confused with other erythematous mucosal lesions or with normal vessels ( Table 18.2 ). Because traumatic and endoscopic suction artifacts may resemble vascular lesions, all lesions must be evaluated immediately on insertion, rather than during withdrawal. “Anemic halos” are often seen surrounding angioectasias of the bowel. Although these halos do not differentiate the various types of vascular lesions, they distinguish true vascular lesions from artifacts. Newer alternative imaging options, such as narrow-band imaging, allow precise discrimination of vascular structures from artifactual mucosal hemorrhage. Punch biopsy samples of vascular lesions obtained during endoscopy are usually nonspecific; the bleeding induced by performing biopsies of these abnormalities is not justified.
Vascular | Nonvascular | Colitis |
---|---|---|
Arteriovenous malformations | Trauma | Ischemic |
Angiomas | Polyps | Infectious |
Phlebectasia | Adenomatous | Radiation (acute) |
Varices | Hyperplastic | Inflammatory bowel disease |
Venous stars | Lymphoid |
Angioectasias may be difficult to visualize during colonoscopy in patients who do not have an optimal bowel cleaning. Because the appearance of angioectasias is influenced by blood pressure, blood volume, and state of hydration, these lesions may not be evident in patients with severely reduced blood volumes or who are in shock until red blood cell and volume deficits are corrected. Cold water lavage of the colon, as is sometimes done to clean the luminal surface from debris during colonoscopy, reportedly may mask these lesions. Meperidine also has been implicated in masking lesions because of a transient decrease in mucosal blood flow. Minimizing use of meperidine and reversal with naloxone to increase the yield of detection has been advocated by some clinicians. Naloxone has been reported to enhance the appearance of normal vasculature in approximately 10% of patients and to cause angioectasias to appear (2.7%) or increase in size (5.4%). Reversal of narcotic analgesia may affect the comfort of an examination, particularly if therapeutics are performed.
Some patients presenting with GI bleeding have no source found by upper endoscopy and colonoscopy, even after second-look endoscopy. In these cases of unexplained chronic GI bleeding, endoscopic examination of the small bowel has been limited by several factors. The length of the small intestine, in addition to its free intraperitoneal location, vigorous contractility, and overlying loops, confounds the usual diagnostic techniques, including barium studies, endoscopic intubation, and identification of specific sites by special imaging techniques of nuclear medicine scans and angiography. The bleeding rate may be slow or intermittent, not allowing identification by either angiography or radionuclide bleeding scan. Because of the inability to localize a bleeding site in the small bowel, patients with obscure GI bleeding from a small bowel source typically presented with prolonged occult blood loss or recurrent episodes of melena or maroon stool without a specific diagnosis. In this group of patients, previous noninvasive tests, such as small bowel follow-through, radioisotope-labeled red blood cell scan, and push enteroscopy, have had suboptimal diagnostic yields of 20% to 40%. Invasive methods, such as laparotomy or intraoperative enteroscopy, may improve the yield up to 70%.
An early diagnosis of the bleeding site has become possible recently with the development of several endoscopic modalities for assessment of the small bowel that include wireless CE and deep small bowel enteroscopy (DBE, single-balloon enteroscopy, and spiral enteroscopy [SE]).
When performing a second-look endoscopy, useful adjunctive diagnostic maneuvers include use of a cap-fitted endoscope to examine blind areas, such as the high lesser curve, under the incisura angularis, and the posterior wall of the duodenal bulb; use of a side-viewing endoscope to examine the ampulla in patients with suspected pancreaticobiliary pathology; and use of a push enteroscope to examine the C-loop of duodenum carefully after injection of glucagon. Although the yield is low (6%), repeat colonoscopy may be useful in the setting of prior poor bowel preparation. Use of naloxone may improve the detection of colonic angioectasias that were not obvious at the index examination. When all the findings on standard examinations (upper endoscopy and colonoscopy) are negative, the small bowel may be presumed to be the source of blood loss. CE should be the third test in the evaluation of patients with GI bleeding ( Fig. 18.2 ). CE, balloon, and spiral enteroscopy, as well as other diagnostic modalities for suspected small bowel bleeding, are discussed in detail in Chapter 17 : Middle Gastrointestinal Bleeding.
Similar to other authors, we recommend CE as a first-line investigation over balloon-assisted enteroscopy in view of its convenience, higher chance to visualize the entire small intestine, and similar diagnostic yield. A recent updated and revised meta-analysis of 10 studies involving 642 patients demonstrated that the pooled overall diagnostic yield for video CE (VCE) and DBE was 62% and 56%, respectively. The diagnostic yield of DBE was significantly higher when performed after a positive VCE compared with negative VCE (75% vs. 27.5%). No test substitutes for good clinical judgment, however, and all small bowel diagnostic studies must be considered in difficult cases of obscure GI bleeding, particularly in a young patient.
In the setting of unexplained overt GI bleeding, CE should be performed close to the bleeding episode. In case of negative CE, we recommend that a second endoscopist reread the CE study. We also recommend a second-look EGD with special attention to areas less optimally examined by CE, especially the duodenum, before concluding with a final diagnosis of obscure GI bleeding. Second-look CE has also been suggested for patients with a prior nondiagnostic CE. Bar-Meir et al (2004) reported that 7 out of 20 patients (35%) who underwent second-look CE had positive or suspicious findings. Another study showed that patients with a nondiagnostic CE test would benefit from a second-look CE if the bleeding presentation changed from occult to overt, or if the hemoglobin value decreased 4 g/dL or more.
The natural history of colonic angioectasias is benign in healthy, asymptomatic individuals, and the risk of bleeding is small. It is estimated that only approximately 50% of colonic lesions ever bleed. There is a risk of bleeding and perforation following attempts at endoscopic obliteration. For all these reasons, in incidentally found angioectasias at all levels of the gut, endoscopic therapy is not warranted.
Pharmacotherapy should be considered whenever endoscopic therapy, surgical intervention, or angiographic therapy is impractical or ineffective, such as in patients in whom the source and the etiology of bleeding are unknown or the pathology is too diffuse to be amenable to ablative therapies.
Nonbleeding AD detected during evaluation of occult bleeding or iron deficiency anemia should be considered to be causative, if no other cause is found. In patients with occult bleeding, bleeding from AD may be more likely in patients who have multiple lesions and a bleeding diathesis (e.g., anticoagulation). As a result, a graduated approach with primary or adjunctive iron-replacement therapy may be initiated, with pursuit of more aggressive therapeutic options guided by the clinical circumstances. The aims of iron-replacement therapy should be to restore hemoglobin levels and mean corpuscular volume to normal, and to replenish body stores.
Numerous oral iron preparations are available, although ferrous sulfate and ferrous gluconate are the preferred forms because of low cost and high bioavailability. A liquid preparation is often tolerated better. Ascorbic acid enhances iron absorption. Parenteral iron should be used when there is intolerance to at least two oral iron preparations or noncompliance, when there is a suboptimal clinical response secondary to suspected iron malabsorption, and when blood transfusion becomes difficult to achieve because of excessive antibodies that challenge crossmatching.
Estrogen-progesterone combination hormonal therapy has been used to treat patients with angioectasias of the GI tract. The effect, which is not immediate, seems to be estrogen dose–dependent. Hormonal therapy acts by enhancing microvascular circulation, coagulation, and vascular endothelial integrity. The most common combination schedule has been ethinyl estradiol 0.01 to 0.05 mg and norethisterone 1 to 3 mg. This therapy should be used in 6-month courses with pauses to reduce the incidence of adverse effects, mostly secondary to the estrogen component. The results of several prospective, controlled trials examining hormonal therapy have been divergent. In a long-term observational study, combination hormonal therapy was shown to stop bleeding in patients with occult GI bleeding of obscure origin, likely to have resulted from small bowel AD. Although uncontrolled studies suggest that combination estrogen-progesterone therapy prevents bleeding episodes secondary to AD, the evidence from the largest placebo-controlled trial to date suggests that this therapy is ineffective. These authors considered that efficacy of hormonal therapy in these patients remains to be proven by a large, randomized, placebo-controlled trial with long-term follow-up.
Reports of efficacy of octreotide in the treatment of AD have been limited to case reports and small series in which a response has been reported in some patients. Octreotide produces vasoconstriction secondary to inhibitory effects on growth hormone and multiple GI vasodilator hormones, and markedly reduces splanchnic blood flow. Its antiangiogenic properties have been shown in different tissues (eye, placenta, liver, and GI neuroendocrine tumors); however, applicability and utility in obscure GI bleeding remain unknown.
The dosage of octreotide can be tapered to the lowest quantity that prevents rebleeding. Response is immediate, and the drug can be administered intravenously (50 µg/hr) or subcutaneously (50–100 µg two or three times a day). Its subcutaneous administration and its longer half-life (90–100 minutes) make octreotide superior to somatostatin and allow use in the outpatient setting. A 6-month course of therapy has been used to treat most patients. A meta-analysis reported by Jackson and Gerson in 2014 including four studies with a total sample size of 77 patients concluded that there is a significant effect on bleeding cessation rates for the somatostatin analogs with a pooled odds ratio of 14.52 (95% confidence interval [CI]: 5.9–36). The standard mean reduction in number of transfusions after 1 year of therapy was 0.55 (95% CI: 0.29–0.82). However, it is difficult to ascertain whether this represents the true effect of octreotide, as this meta-analysis had some inherent weaknesses.
Sandostatin LAR Depot (Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a depot formulation of octreotide for long-term maintenance therapy currently approved for acromegaly and GI and pancreatic neuroendocrine tumors. Compared with conventional octreotide, Sandostatin LAR Depot is administered at a dose of 20 mg intramuscularly once a month with a similar efficacy and safety profile. Sandostatin LAR Depot does not require hospital admission, which makes it an attractive outpatient option for long-term therapy in patients with chronic GI bleeding, but is more expensive than conventional octreotide.
Thalidomide is a drug with powerful immunomodulatory, antiinflammatory, and antiangiogenic effects that was withdrawn from the market in the 1960s because of its teratogenicity. It has been reintroduced more recently and has been demonstrated to inhibit VEGF-dependent angiogenesis. Thalidomide administered orally at a variable dose of 100 to 300 mg/day is an innovative and promising therapeutic option for GI bleeding associated with AD and can be used in refractory cases or when other drugs or therapies are contraindicated. Thalidomide is contraindicated in patients with peripheral neuropathy and pregnant women and women with childbearing potential because of its teratogenic effects, and it should be used cautiously in patients with cardiovascular or neurologic disorders and hepatic or renal impairment. Owing to its immunosuppressant activity by blocking tumor necrosis factor, use of thalidomide may also be discouraged in patients at risk for infection or chronic infectious disease, especially patients with HIV infection. In all these clinical settings, Sandostatin LAR Depot may be safer than thalidomide.
Two recent studies explore the use of thalidomide for gastrointestinal angiodysplastic lesions (GIADs) in a series of patients. The first study from China in 2011 randomized patients to 100 mg of thalidomide versus iron therapy for 4 months and demonstrated efficacy when rebleeding rates and transfusional requirements were analyzed. The second study from Spain treated 12 refractory patients and demonstrated an increase in hemoglobin values after 4 months.
Other agents that have been used for management of angioectasias with limited available data include tranexamic acid, danazol, desmopressin, and recombinant activated factor VII.
The goal of endoscopic therapy is thrombosis of the bleeding vessel. Studies directly comparing the effectiveness of the different approaches have not been performed. The approach depends on the location of the lesion, the experience of the endoscopist, and the availability of equipment.
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