Keywords

Introduction

Occult gastrointestinal (GI) bleeding refers to the presentation of a positive fecal occult blood test without an obvious cause for the blood loss [1]. Once a patient presents with occult GI bleeding, it is important to determine if iron deficiency anemia is present. In patients with a positive fecal occult blood test but no evidence of anemia, a colonoscopy should be considered. In patients with upper GI symptoms, an upper endoscopy should be performed as well [2, 3]. Upper GI symptoms include heartburn, difficulty swallowing, stomach pain, nausea, and vomiting [4]. For patients who have a positive fecal occult blood test and an iron deficiency anemia, both an upper endoscopy and colonoscopy are recommended [2, 3]. If upper endoscopy and colonoscopy do not indicate the source of the bleeding, the next step is to evaluate the small bowel [5]. The majority of these patients will undergo a wireless capsule endoscopy [6].

Upper Endoscopy

Upper endoscopy allows for the visualization of the esophagus, stomach, and proximal duodenum. It can also be used to sample tissue [7]. Typically upper endoscopies are performed using a high-definition white light endoscope [8]. Patients with upper GI symptoms, especially symptoms indicative of gastroesophageal reflux disease (GERD), often receive upper endoscopies [9]. In addition, if imaging of the upper GI tract shows suspected neoplasms, ulcers, strictures, mucosal abnormalities, or obstructions, an upper endoscopy may be performed [7]. Lesions in the upper digestive tract are often detected in those who test positive for fecal occult blood or have an iron deficiency anemia [10,11,12,13]. Upper GI symptoms are also associated with the detection of lesions in the upper digestive tract. However, the prevalence of lesions in the upper GI tract is greater than or equal to that of colonic lesions even in those without symptoms [10,11,12,13]. Upper GI sources of bleeding are found in 36–56% of patients with an iron deficiency anemia [14,15,16] and in 29% of patients who test positive for fecal occult blood and do not have an iron deficiency anemia. Approximately 50% of these patients will be symptomatic [14]. In addition, 5–17% of patients have both upper and lower GI lesions [14,15,16]. Upper endoscopy can employ a number of therapeutic interventions including biopsy, polypectomy, dilation of strictures, stent placement, removal of foreign bodies, percutaneous gastrostomy tube placement, treatment of GI bleeding with injection, banding, coagulation, sclerotherapy, and endoscopic therapy for esophageal intestinal metaplasia [7].

Colonoscopy

Colonoscopy is the preferred approach for evaluation of the colon, rectum, and the distal portion of the terminal ileum and can detect a wide range of lesions, including polyps, diverticula, cancers, and angiodysplasias. It allows for the visualization of the entire colonic mucosa as well as the ability to obtain tissue biopsies [17]. While colonoscopy is effective in reducing colon cancer rates overall, it is more effective in reducing the risk of rectal and left sided colon cancer than right sided colon cancer [18]. One technique to improve visualization is retroflexion, which is when the colonoscope is bent into a U-shape to allow the viewing lens to look backwards. Reflexion is often used in the right colon to improve the effectiveness of colonoscopy given the fact that right sided colon polyps can be located on the backs of haustral folds in the cecum and ascending colon [19]. Retroflexion in the right colon is successful in over 90% of cases with very low complication rates while yielding a significant improvement in the adenoma detection rate [20]. Good bowel preparation is important for all colonoscopies and is necessary for proper visualization. An excellent bowel prep will allow for 95% of the mucosal surface to be seen allowing for a high adenoma detection rate while a poor bowel prep will result in fecal matter blocking visualization and require a repeat bowel preparation [21]. Diagnostic indications include screening or surveillance for colon cancer, evaluating signs and symptoms suggestive of colonic or distal small bowel disease such as gastrointestinal bleeding or diarrhea, assessing a response to treatment for patients with colonic diseases like inflammatory bowel disease, and evaluating abnormalities found on imaging studies [17] including barium enema [22], abdominal computed tomography (CT) [23], positron emission tomography (PET) [24], and magnetic resonance imaging (MRI) [25]. Some radiographic findings that are considered abnormal and may warrant performing a colonoscopy include thickening of the wall of the colon or terminal ileum [26], mass lesions [27], and strictures [28]. It also can be used for therapeutic interventions, such as stricture dilation, stent placement, colonic decompression, and foreign body removal [17]. Colonoscopies are generally considered the gold standard for colon cancer screening and surveillance. If polyps are found during the colonoscopy, they are usually removed endoscopically if possible [29].

Small Bowel Evaluation

If a complete endoscopy and colonoscopy with adequate visualization do not reveal the source of occult gastrointestinal bleeding, evaluation of the small bowel is recommended [1]. Wireless capsule endoscopy is the preferred initial approach for evaluating the small bowel [1]. Other endoscopic options include push enteroscopy [30], single balloon endoscopy, double balloon endoscopy [31] and spiral enteroscopy.

Wireless Capsule Endoscopy

Wireless capsule endoscopy is generally the first choice for evaluating suspected small bowel bleeding. Wireless video endoscopy, also referred to as video capsule endoscopy (VCE), is a noninvasive technology designed to provide diagnostic imaging of the small intestine. It can also provide limited visualization of the esophagus, stomach, and cecum. The images acquired from wireless capsule endoscopy are of high resolution and have a 1:8 magnification, which is greater than that of a conventional endoscope. This allows for visualization of individual villi. The capsule moves passively, does not inflate the bowel, and images the mucosa in a collapsed state [31]. The main advantages of wireless capsule endoscopy are that it is relatively noninvasive and permits examination of the entire length of the small bowl most of the time. Its main disadvantage is that it cannot be guided nor steered and it does not allow for tissue sampling or therapeutic intervention. In addition, not all of the small bowel mucosa is visualized as the capsule passes through the small intestine while being pushed along by peristalsis [31]. The diagnostic yield of capsule endoscopy is highest when it is performed as close as possible to the bleeding episode [32,33,34,35]. Double-ended wireless video capsules, which can capture images from both ends of the video capsule, have also been developed for the examination of the colon [36].

Wireless video endoscopy identifies causes of small bowel bleeding more often than push enteroscopy in most reports [37,38,39,40,41,42,43,44,45]. Studies have suggested that wireless capsule endoscopy is equal to or more sensitive than other methods for the diagnosis of small bowel sources of blood loss. A meta-analysis of 14 observational studies compared wireless capsule endoscopy with other procedures for suspected small bowel bleeding and estimated that the overall yield of wireless capsule endoscopy was 63%, which is significantly higher than push enteroscopy with a yield of 26% and barium studies with a yield of 8% [37]. Overall, the yield of wireless video endoscopy for occult small bowel bleeding has been reported to be in the range of 30–70% [6, 32, 33, 37,38,39,40, 42, 46,47,48,49,50,51,52]. One trial of 89 patients with suspected small bowel bleeding that compared capsule endoscopy with push enteroscopy found that performing capsule endoscopy before push enteroscopy was a more effective strategy than beginning with push enteroscopy. The capsule endoscopy first strategy significantly reduced the percentage of patients needing a second procedure from 79% to 25% [53]. In another randomized trial of 136 patients with suspected small bowel bleeding who had undergone upper endoscopy, colonoscopy, and push enteroscopy, patients were assigned to either capsule endoscopy or radiographic evaluation. The diagnostic yield for capsule endoscopy was 30% in comparison to radiographic evaluation with a 7% yield, but the rate of recurrent bleeding between the two groups was the same [48]. Another study involving 305 patients undergoing capsule endoscopy for suspected small bowel bleeding did not find a significant difference between those with a positive and negative video capsule endoscopy. It also did not find a difference in rebleeding rates between those who underwent treatment and those who did not [54]. Repeat capsule endoscopy is recommended for patients whose initial capsule endoscopy is negative given that the entire small bowel mucosa may not be visualized with a single pass and could miss the source of GI bleeding. The capsule does not follow an axial path but rather tumbles and is unable to see behind all of the folds of the small intestine [55].

Push Enteroscopy

Push enteroscopy is an alternative means of visualization of the small bowel. It involves oral passage of a push enteroscope or a pediatric colonoscope past the ligament of Treitz. In the case of the enteroscope, the instrument is 200–250 cm long but the depth of insertion can be limited by looping within the stomach or small bowel or by patient discomfort. About 25–80 cm of the jejunum distal to the ligament of Treitz can be evaluated [56]. The amount of jejunum that can be viewed can be increased when an overtube designed to reduce looping in the stomach is used. However, it has not been conclusively determined whether or not this improves the diagnostic and therapeutic ability of push enteroscopy [57, 58].

Multiple studies have determined that the diagnostic yield of push enteroscopy in identifying bleeding lesions is estimated to be between 3% and 70% [2] with angioectasia being the most common diagnosis [59,60,61]. One benefit of push enteroscopy in comparison to wireless capsule endoscopy is that it can sample tissue and perform therapeutic maneuvers which include clipping of bleeding lesions or ablation and hemostasis of bleeding using bipolar cautery.

In a study of 95 patients with suspected small bowel bleeding who underwent push enteroscopy, it was concluded that many lesions detected during enteroscopy were within reach of a standard endoscope. This indicates that a careful repeat standard upper endoscopy may be appropriate prior to push enteroscopy or other diagnostic procedures [59].

Single Balloon

Single balloon enteroscopy allows for both evaluation and therapeutic intervention in the small bowel. Single balloon enteroscopy consists of a long, 1400 mm enteroscope, an overtube with a distal inflatable balloon, and a control unit to inflate and deflate the balloon. The overtube is designed to minimize looping of the small bowel while pleating it back over the overtube and the enteroscope [62]. It can be used anterograde via the mouth or retrograde via the rectum with intubation and advancement proximal to the ileocecal valve. Single balloon enteroscopy is typically performed with fluoroscopic assistance and the use of CO2 instead of air for insufflation of the bowel as CO2 is absorbed more quickly across the bowel mucosa (Fig. 3.1). Using air for the insufflation of the bowel can prolong the procedure time and single balloon enteroscopy requires higher volumes of gas insufflation, which can cause discomfort and limit advancement of the enteroscope [62]. Bowel prep is not required for enteroscopy. The enteroscope is initially advanced as far as possible using the same technique as a standard endoscope. The tip of the enteroscope is hooked on a fold in the bowel to stabilize it and the overtube is then advanced over the enteroscope. The balloon is inflated and both the enteroscope and overtube are withdrawn together. The balloon is deflated and the enteroscope is then advanced as far as possible at which point the process is repeated [62]. This results in pleating of the bowel over the overtube and subsequent shortening of the bowel. The combination of anterograde and retrograde enteroscopy can potentially allow for complete evaluation of the small bowel. Single balloon enteroscopy is a safe procedure with <1% risk of perforation during diagnostic procedures [62].

Fig. 3.1
figure 1

Fluoroscopic image of single balloon enteroscopy

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Double Balloon

Double balloon enteroscopy is similar to single balloon enteroscopy. The primary difference is that the enteroscope has a distal balloon in addition to the overtube balloon. The enteroscope is advanced as far as possible and the balloon is inflated to anchor its position [56]. The overtube is then advanced towards the end of the enteroscope at which point the overtube balloon is inflated and both enteroscope and overtube are withdrawn together pleating the bowel in an accordion like fashion over the overtube. The enteroscope balloon is deflated and the process is repeated. Double balloon enteroscopy allows for complete evaluation of the jejunum and ileum [56]. It is typically done in an antegrade fashion but can be done retrograde via the rectum. Diagnostic yields for obscure GI bleeding range from 40% to 80% [56]. Perforation is rare but is more common in patients who have had prior bowel surgery. Pancreatitis has been reported as a complication of double balloon enteroscopy as well [56].

Spiral Enteroscopy

Spiral enteroscopy allows for antegrade evaluation of the small bowel. It involves an overtube with a soft raised helix at its distal end. The enteroscope is manually turned in a clockwise manner to cause pleating of the small bowel on the enteroscope [63]. It has a shorter examination time in comparison to double-balloon and single-balloon enteroscopy as well as more stability during withdrawal but it requires two operators [64]. Motorized spiral enteroscopy have recently been developed that would allow for single operator use [65]. The drive motor is located in the endoscope handle and is activated by foot pedals, which controls the direction and speed of rotation of a coupler located in the middle of the endoscope’s insertion tube [66]. Studies have shown that motorized spiral enteroscopy have short procedural durations and high depth of maximum insertion while maintaining a high diagnostic and therapeutic efficacy [67].

Type

Overtube

Depth of Insertion

Procedure time

Completion Rate*

Diagnostic Yield

Capsule

No

Reaches cecum 85% of the time [68]

480 min [68]

51.2–94.2% [69,70,71]

48–60.9% [69, 72]

Push

Can be with or without [73]

46–80 cm beyond the ligament of Treitz with overtube [44, 57, 60, 74,75,76,77,78,79,80]

30 min [60, 74, 75]

0%

15–80% [81, 82]

Single balloon

Yes

Antegrade: 133–270 cm

Retrograde: 73–199 cm [83,84,85,86,87]

53–69 min [86, 88]

0–24% [83, 89,90,91]

41–65% [83,84,85,86,87, 89,90,91,92,93]

Double balloon

Yes

Antegrade: 220–360 cm

Retrograde: 124–183 [94,95,96,97,98]

73–123 min [94,95,96,97,98]

92% [95, 97,98,99,100,101,102,103]

40–80% [88,89,90,91,92, 104]

Spiral

Yes

175–262 cm (anterograde or retrograde) [105,106,107]

34–37 min [105,106,107]

8–92.6% [103, 108]

12–75% [64, 83,84,85,86,87, 89,90,91,92,93, 105,106,107]

  1. *Total small bowel visualization

Intraoperative Enteroscopy

Intraoperative enteroscopy involves the insertion of an endoscope through an enterotomy site, orally, or rectally during surgery [109, 110]. The surgeon telescopes the bowel over the endoscope, allowing for visualization of the entire length of the small bowel in more than 90% of patients. The diagnostic yield has been reported to be between 60% and 88% with rates of recurrent bleeding of 13–60% [2]. There can, however, be associated morbidity and mortality. Complications from intraoperative enteroscopy including serosal tears, avulsion of the superior mesenteric vein, congestive heart failure, azotemia, and prolonged ileus have been reported [110]. A large, multidisciplinary study looking at intraoperative enteroscopy for patients who had bleeding or anemia had a diagnostic yield of 69%. Segmental resection was performed in 90% of these patients with a symptom recurrence rate of 20%. There were no serious complications reported [111].

Technical Aspects

Endoscope technology has seen significant advances in recent years. Available endoscopes in the United States have been designed with improved resolution and magnification compared to earlier models, thus allowing for the ability to distinguish submillimeter closely approximated lesions. Upper endoscopes generally have outer diameters of 9.2–10.8 mm with slimmer 5.8 mm diameter endoscopes available for specific clinical situations such as esophageal strictures. Working lengths range from 1030 mm to 1100 mm allowing for intubation of the third portion of the duodenum (Fig. 3.2).

Fig. 3.2
figure 2

Olympus GIF 190 upper endoscope

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Available colonoscopes have outer diameters ranging from 9.5 mm for pediatric colonoscopes to 13.2 mm for adult colonoscopes depending on the manufacturer. Field of vision is generally 140 degrees up to 170 degrees for some colonoscopes [112] (Fig. 3.3).

Fig. 3.3
figure 3

Olympus CF 190 colonoscope

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A pixel is defined as a tiny area of illumination on a display screen. Standard Resolution (SD) is defined as a 4:3 (width: height) aspect ratio with a 640 × 480 pixel lines resulting in over 300,000 pixels to produce the image. Modern endoscopes allow for high definition (HD) imaging which produces increased image detail and thus the ability to discern more subtle mucosal lesions. HD endoscope systems allow for 1080 × 1024 up to 1920 × 1080 pixel format. In addition to high definition, many endoscopes have variable degrees of magnification as well as a near focus mode to improve detection of subtle lesions [112].

Endoscopes have left/right and up/down controls which allow for angulation of the tip (Fig. 3.4). A working channel allows for the use of various instruments such as biopsy forceps, snares, and coagulation devices to be passed through the endoscope (Fig. 3.5). Water irrigation and suction are also available to help clear visual fields of fecal residue or blood (Fig. 3.6). Variable stiffness colonoscopes allow for adjustment of the stiffness of the colonoscope to reduce looping [113] (Fig. 3.7).

Fig. 3.4
figure 4

Colonoscope control knobs

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Fig. 3.5
figure 5

Working channel cap

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Fig. 3.6
figure 6

Colonoscope tip with suction, irrigation, and biopsy channels

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Fig. 3.7
figure 7

Variable stiffness control

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Looping during colonoscopy most commonly occurs in the sigmoid colon and transverse colon, which results in paradoxical retrograde or static movement of the colonoscope relative to the bowel during antegrade intubation of the bowel. Looping is often associated with “redundant” colons and can reduce cecal intubation rates. Cecal intubation rates for endoscopists are a quality measure and should be at least 90–95% [114]. Risk factors for failure to reach the cecum include poor bowel preparation and female sex. Women have longer colons relative to men, increasing the risk of looping during colonoscopy [115]. Once the cecum has been reached, the colonoscope is slowly withdrawn using maneuvers that allow for careful inspection of the mucosa and haustral folds. The colonoscope is retroflexed in the rectum by bending backwards on itself to inspect the distal rectum. A similar maneuver is used in upper endoscopy to look back up at the cardia of the stomach, which is not well seen upon entering the stomach from the esophagus if only a forward view is utilized [116].

Endoscopic technology that enhances visualization of the mucosa and microvasculature compared to white light endoscopy has also been developed. Narrow Band Imaging utilizes an electronically activated filter allowing only blue and green light [117], which is absorbed by hemoglobin thus making blood and vascular structures dark and enhancing differences between the mucosa and the surrounding vasculature [118]. This technology has improved the detection of flat or carpet-like polyps and the ability to differentiate neoplastic from non-neoplastic tissue [119].

Endoscopies are not without risks. Preprocedural complications that arise from preparation for an endoscopy include respiratory distress or arrest from sedation, possibly with oxygen saturation dropping below 80% [120] as well as potential medication allergic reactions and side effects, such as cardiorespiratory complications from using diazepam (Valium) and midazolam (Versed) [121]. Midazolam is commonly used for conscious sedation and has been known to cause grand mal seizures [122]. Bowel preparations also come with a variety of potential complications, which include hypoglycemia in diabetic patients since the patient is required to be NPO for 6–8 hrs before the procedure and fluid and electrolyte imbalances can result from the preparations. Examples of electrolyte imbalances include hyperphosphatemia following a phosphate bowel preparation, especially in patients with renal failure [123], hypocalcemia [124], and hypovolemia. The use of topical anesthetic agents run the risk of disruption in pharyngeal motor function [125], angioneurotic edema, and in the case of using topical benzocaine, acute toxic methemoglobinemia [126].

Colonoscopies have a number of potential procedural complications. Perforation is estimated to occur in approximately 0.2% of diagnostic colonoscopies. One retrospective review found that 64% of perforations are rectosigmoid and 13% are cecal [127]. Perforation may be due to direct mechanical trauma from force at the tip of the endoscope or pneumatic distension when intraluminal pressure exceeds 210 mmHg [128]. In therapeutic colonoscopy, there is deliberate mucosal injury when performing a polypectomy or biopsy, which may directly cause perforation. As a result, the site of perforation in a polypectomy is most commonly the site of the polyp. Hemorrhage, endocarditis [129], bacteremia [130], splenic injury [131], and vasovagal reactions are other risks of colonoscopies.

The most serious complications involving upper endoscopies are perforation and hemorrhage. Perforations during upper endoscopies occur at a rate of 0.02–0.2% [125]. The most common site for perforation is the distal third of the esophagus [132]. Angulation of the posterior wall of the stomach may make it difficult to navigate and the distal third of the esophagus is most likely to be inflamed or have a tumor. Other risks include infection, aspiration, Mallory-Weis tears [133], and cardiac dysrhythmia [134].