【经验】不明原因消化道出血的处理策略

哈佛医学院John R. Saltzman 博士

不明原因消化道出血是消化道出血的一种类型，它包括多种自然病史，预后，以及处理措施。我们如此定义不明原因消化道出血：持续性或反复发生的消化道出血，并且经上消化道内镜和结肠镜检查未发现明显病因（辐射性检查不再需要，如小肠钡餐造影）。另外，将不明原因消化道出血分为显性和隐性两种亚组是很有帮助的，前者是指出血症状肉眼明显，常见于便血、褐色样便、黑粪症，后者是指肉眼看不见的出血，常见于伴有或不伴有缺铁性贫血的粪便潜血实验阳性。

背景

不明原因消化道出血在消化道出血患者中发生率为5%，发病部位大部分（75%）位于小肠。对于轻度不明原因消化道出血，或者那些出血速度较慢但并发症明显的患者，目前没有额外的诊断检查，恰当的治疗措施是补铁和/或输血的保守治疗。

诊断

1. 无线摄像胶囊内镜在诊断不明原因消化道出血的出血来源方面发挥重要作用，胶囊内镜可以窥视整个小肠。严重消化道出血患者经上消化道内镜和结肠镜检查后，接下来应行胶囊内镜检查。

2. 有小肠梗阻病史或者怀疑小肠梗阻时进行胶囊内镜检查需谨慎，因为胶囊会被卡在梗阻部位上方。中到高度可疑小肠狭窄的患者，须先用探路胶囊（一种不透明的可分解的胶囊）评估是否存在严重狭窄。

3. 胶囊内镜检查阴性的严重消化道出血患者，我会重复行上消化道内镜（或推进式小肠镜检查）和结肠镜检查，寻找在第一次检查时可能错过的微小病变。

4. 选择哪种内镜进行复检依赖于现有症状，例如，便血极有可能是低位消化道出血，而咯血极有可能是上消化道出血。黑粪症没有特异性部位。

5. 上消化道内镜检查可能会发现很多初次检查时错过的诊断，包括卡梅伦溃疡（食管裂孔疝溃疡或糜烂），杜氏病，胃窦血管扩张（西瓜胃），动静脉畸形，胰源性出血，主动脉-肠瘘。我建议重复行上消化道镜检的时候行推进式小肠镜，并在重复进行上消化道内镜检查时使用侧面视野。小肠活检可以用来排除乳糜泻。

6. 结肠镜检查也可能会发现很多初次检查时错过的诊断（尤其是准备一般或较差时），包括血管病变，杜氏病，憩室出血，痔疮，炎症性肠病，放射性直肠炎，极少数可能会发生在出血性结肠息肉或肿物。

7. 若患者高位和低位消化道出血来源都被排除，行胶囊内镜也未发现出血来源，须行深度小肠镜检查。深部小肠镜包括双气囊小肠镜，单气囊小肠镜，以及螺旋小肠镜。隐性不明原因消化道出血患者由于临床症状不明显，因此临床观察是合乎情理的。然而，显性不明原因出血患者应行深部小肠镜检查。

8. 一般而言，如果出血来源尚不明确，最好自上端开始行深部小肠镜检查，因为这样的路线可看到小肠近端三分之二部分。如果这样检查结果显示为阴性，或者胶囊内镜提示出血来源位于小肠远端三分之一处，应自下端行深部小肠镜检查。

9. 胶囊内镜发现消化道出血来源时，接下来须行深部小肠镜以便确诊，提供可能的治疗，或者用于手术之前标记出血部位。而且，如果出血部位不确定，我们标记好可能性最大的部位，这样进一步检查时可以此为指导，例如从另一个方向行深部小肠镜时，重复行胶囊内镜检查时，或者手术时。

10. 小肠出血来源因年龄而变化。和大部分疾病不同，与年老患者相比，年轻患者消化道出血原因往往是肿瘤（多为良性）。

11. 年龄小于40的患者更可能患有小肠肿瘤（消化道间质瘤、淋巴瘤、类癌）和炎症性肠病，杜氏病，或者Meckel憩室。

12. 年老患者更倾向于血管损伤导致出血，包括血管病变，药物所致糜烂（NSAIDs）。肿瘤也是老年患者出血的原因。

13. 出现口唇或者口咽毛细血管扩张意味着遗传性出血性毛细血管扩张症的可能（如sler-Weber-Rendu综合征）。

14. 一般在内镜检查包括摄像胶囊内镜未明确诊断之后行放射学检查。放射学检查有CT，或磁共振肠道成像（专用于排除小肠肿瘤和小肠静脉曲张），或双相或三相多探头CT扫描，可以发现并定位出血活跃的部位。

15. Meckel扫描（静脉注射99mTc同位素的高锝酸盐，它可以与胃粘膜结合，然后放射追踪，辨别出大部分Meckel憩室中胃粘膜异常的区域）应在年轻（年龄＜50岁）的严重的显性不明原因消化道出血患者中进行，以及经过内镜检查包括胶囊内镜未发现出血来源的患者。

16. 血管造影往往在扫描结果为阳性后进行，一般用于持续性的严重出血（需要输血）的、出血来源尚未明确的患者，以及为可能的治疗提供帮助。

17. 在手术期间行内镜检查很少见，仅针对那些不能用任何其他方法学手段定位出血点，而且出血持续的严重消化道出血患者。

治疗

1. 治疗应该直接针对潜在损伤部位，因此明确出血来源十分必要。

2. 内镜治疗是指注射肾上腺素，烧灼出血点，或放置止血夹，或者各种方法联合。小肠血管病变往往用氩等离子凝固烧灼治疗。

3. 血管造影和手术一般用于持续出血的患者，经大量检查后仍未发现明确出血来源的患者，内镜治疗无反应的患者，损伤部位明确但是对保守治疗无反应的患者（如Meckel憩室和小肠肿瘤）。

Obscure gastrointestinal (GI) bleeding is a category of GI bleeding that includes a variety of conditions with variable natural histories, prognoses, and management strategies. It can be defined as GI bleeding that is persistent or recurrent without an obvious etiology following upper endoscopy and colonoscopy (radiologic studies such as a small bowel follow-through are no longer required). In addition, it is useful to further subcategorize obscure GI bleeding as overt obscure and occult obscure, with the former being evident bleeding that manifests as hematochezia, maroon stools, or melena, and the latter being without visible GI bleeding that manifests only by guaiac-positive stool with or without iron deficiency anemia.

Background

Obscure GI bleeding occurs in about 5% of patients with GI bleeding.
The location of most causes of obscure GI bleeding (75%) is the small bowel.
In patients with trivial amounts of obscure bleeding or in those with significant comorbidities with slow rates of blood loss, no additional diagnostic testing and conservative management with iron supplementation and/or transfusions may be appropriate.

Diagnosis

Wireless video capsule endoscopy has a central role in determining the source of obscure GI bleeding as it can visualize the entire small bowel. Capsule endoscopy should generally be the next step after upper endoscopy and colonoscopy in a patient with significant GI bleeding.

Be careful of performing capsule endoscopy if there is a history of or a suspicion of a small bowel obstruction, as the capsule can get caught above the obstruction. In patients in whom there is a moderate to high suspicion of a small bowel stricture, a patency capsule (a collapsible shell of the capsule that is radio-opaque) can be first given to the patient to assess if there is a significant stricture.

In patients with a negative capsule endoscopy study and significant GI bleeding, I repeat the upper endoscopy (or perform push enteroscopy) and colonoscopy examinations, looking for subtle lesions that could have been missed on the initial examinations.

The choice of which endoscopic procedure to repeat may depend on the presenting symptoms; for example, hematochezia is more likely to have a lower GI source whereas hematemesis strongly suggests an upper GI location. Melena is not a specific localizing symptom.

Upper endoscopy may reveal several diagnoses that could have been missed on initial examination, including Cameron ulcers (ulcers or erosions in a hiatus hernia), a Dieulafoy’s lesion, gastric antral vascular ectasia (watermelon stomach), AVMs, hemosuccus pancreaticus, and aorto-enteric fistula. I consider doing a push enteroscopy as well as using a side-viewing scope when repeating an upper endoscopy. Biopsies of the small bowel can be obtained to exclude celiac disease.

Colonoscopy may also reveal several diagnoses that could have been missed on initial examination (especially if the preparation was fair or poor) including angioectasias, a Dieulafoy’s lesion, diverticular bleeding, hemorrhoids, inflammatory bowel disease, radiation proctitis, and, less likely, a bleeding colonic polyp or mass.

In patients without a source of bleeding seen on capsule study in whom both upper and lower GI bleeding sources have been excluded, deep small bowel enteroscopy can be performed. Deep small bowel enteroscopy includes double-balloon enteroscopy, single-balloon enteroscopy, and spiral enteroscopy. In those with obscure occult GI bleeding that is not clinically significant, it is reasonable to observe the clinical course. However in those with overt obscure bleeding, deep small bowel enteroscopy should be performed.

It is generally best to start with deep small enteroscopy from above if the source has not been identified, as this route typically allows visualization of the proximal two-thirds of the small bowel. If this test is negative or if a capsule endoscopy shows a source in the distal third of the small bowel, deep small bowel enteroscopy from below is indicated.

In patients with a source of GI bleeding seen on video capsule endoscopy, a deep small bowel enteroscopy is usually the next step to confirm the diagnosis, provide possible therapy, or to mark/tattoo prior to surgery. In addition, if the bleeding site is not identified, the point of maximal insertion is often marked with a tattoo such that further evaluations can use this as a guide, such as for a deep enteroscopy from the other direction, repeat capsule endoscopy examination, or surgery.

Possible small bowel sources are dependent on age. Unlike most other conditions, young patients are more likely to have tumors (usually benign) as a source of the GI bleeding compared with older patients.

Patients younger than 40 years of age are more likely to have small bowel tumors (GI stromal tumors, lymphoma, and carcinoid) as well as inflammatory bowel disease, a Dieulafoy’s lesion, or a Meckel’s diverticulum.

Older patients are more likely to bleed from vascular lesions including angioectasias and erosions due to medications (NSAIDs). Tumors can also be the source of bleeding in older patients.

The presence of telangiectasias on the lips or of the oropharynx suggests the possibility of bleeding due to hereditary hemorrhagic telangiectasia (eg, Osler-Weber-Rendu syndrome).

The role of radiology is typically after endoscopic examinations including video capsule endoscopy have been performed and are non-diagnostic. Possible radiological tests include CT or MR enterography (especially to exclude small bowel tumors and small bowel varices) or dual- or tri-phase multi-detector CT scans, which can detect and localize active bleeding.                                                                     

Meckel’s scans (which involve the IV administration of 99mTc pertechnetate, which binds to gastric mucosa, followed by scintigraphy to identify areas of ectopic gastric mucosa that is found in most Meckel’s diverticula) should be considered for younger patients (<50 years of age) with significant overt obscure GI bleeding and no source seen on endoscopic examinations including video capsule endoscopy.

Angiography often after a positive bleeding scan is reserved for patients with ongoing severe (transfusion-requiring) GI bleeding in whom a definitive source has not been localized and for possible therapy.

Intra-operative enteroscopy is rarely needed for those patients in whom a source cannot be localized by any other methodology and who continue to experience significant GI bleeding.

Treatment

Treatment should be directed toward the underlying lesion, and thus it is imperative to identify the source of bleeding.

Endoscopic treatment is with injection of epinephrine, cautery, or hemoclips placement, or a combination of methods. Small bowel angioectasias are most commonly treated with cautery using argon plasma coagulation therapy.

Angiography and surgery are generally reserved for those with ongoing bleeding, those with no defined source after extensive testing, those who do not respond to endoscopic therapy, and those whose lesions are identified but not responsive to more conservative therapy (such as Meckel’s diverticulum and small bowel tumors).      

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