Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance and a Closer Look at the Esophagus

Abstract

Upper gastrointestinal endoscopy is the most important test used to diagnose esophageal disease. Proper insertion of the endoscope is essential for accurate examination of the esophagus. However, due to coughing or the gag reflex, esophageal examinations can be difficult. Further, when a central ridge is present in the middle of the pyriform sinus, careful approach is necessary. Chromoendoscopy of the esophagus includes acetic acid chromoendoscopy for Barrett’s esophagus and lugol’s iodine chromoendoscopy for squamous cell carcinoma. In recent times, electronic chromoendoscopy is widely used. In this chapter, diagnosis and treatment of various esophageal diseases including esophagitis, Barrett’s esophagus, adenocarcinoma, squamous cell carcinoma, diverticulum, inlet patch, hiatal hernia, polyps, subepithelial lesions, and varix are discussed.

1. Introduction

Upper gastrointestinal endoscopy is the most important test for the diagnosis of esophageal disease. Accurate diagnosis is crucial for appropriate treatment of esophageal diseases, including surgical intervention. With advancements in the surgical treatment of esophageal diseases, the importance of upper gastrointestinal endoscopy has been increasing. In this chapter, the endoscopic techniques used in the examination of the esophagus are discussed.

2. Insertion technique

During endoscope insertion, the cough or gag reflex is induced and the movement of the esophageal lumen increases, thereby making esophageal examination difficult. Therefore, proper endoscope insertion is essential for accurate examination of the esophagus.

The first obstacle encountered during endoscope insertion is the uvula. Access to the pyriform sinus can be gained without difficulty if the endoscope is carefully inserted to the right or left of the uvula, taking care not to make contact with the centrally placed uvula. The second and most difficult part of endoscope insertion is the insertion of the endoscope into the pyriform sinus. This part is sometimes problematic for beginners, as well as for board-certified endoscopists. Upon reaching the left pyriform sinus, a slight clockwise rotation of the scope with gentle pressure is recommended for insertion in the left pyriform sinus [1]. This technique is successful in most cases; however, in some patients with anatomical variations, endoscopists experience severe resistance that may lead to bleeding or even perforation. Two types of pyriform sinus are shown in Figure 1. In Figure 1a, there is no central ridge; thus, the clockwise rotation technique can be used. In contrast, in Figure 1b, a central ridge is present in the left pyriform sinus, and the true lumen is more medial than normal, but its path runs upward (i.e., medially). After traversing the pyriform sinus, the path goes downward (i.e., laterally). Thus, performing the clockwise rotation technique without checking for the central ridge can result in severe pyriform sinus injury. Further, air insufflation is needed to determine the presence of a central ridge.

Figure 1.

Two types of pyriform sinus. (a) Left pyriform sinus without central ridge. (b) Left pyriform sinus with central ridge.

3. Chromoendoscopy

Chromoendoscopy entails the application of a chemical substance to the mucosal surface of the gastrointestinal tract to facilitate visualization and detection of dysplastic and malignant lesions [2]. Since the recent introduction and adoption of virtual chromoendoscopy methods such as narrow-band imaging (NBI), the importance of dye-based chromoendoscopy in day-to-day clinical practice has been decreasing [3]. Nevertheless, chromoendoscopy remains important in many clinical conditions. In this chapter, some chromoendoscopy methods still used in esophageal endoscopy will be discussed.

3.1 Acetic acid chromoendoscopy for Barrett’s esophagus (BE)

Acetic acid is a weak acid that breaks up the disulfide bridges of glycoproteins of the mucus layer, resulting in protein denaturation and surface pattern enhancement [2]. BE is a known risk factor of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Current nondysplastic BE surveillance guidelines recommend that random four-quadrant biopsy specimens be taken every 1–2 cm to check for dysplasia [4]. Due to the time-consuming and labor-intensive nature of the procedure, the American Society for Gastrointestinal Endoscopy Technology Committee released the Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) criteria for nondysplastic BE surveillance. These criteria help determine which advanced imaging technique with targeted biopsy can replace the current surveillance guidelines for the detection of HGD and EAC. The performance thresholds in the PIVI criteria are per-patient sensitivity ≥90%, negative predictive value ≥98%, and specificity ≥80% [1]. Based on these criteria, only acetic acid chromoendoscopy, NBI, and confocal laser endomicroscopy can replace the current guidelines [4]. However, the use of acetic acid chromoendoscopy is on the decline due to the long procedural time, uneven distribution of dye over the mucosa, and high interobserver variability due to lack of classification [5].

3.2 Lugol’s iodine chromoendoscopy

Lugol solution is an iodine-based solution used in the detection of dysplasia and cancer in squamous epithelia. Since iodine binds to glycogen, which is abundant in nonkeratinized squamous epithelium, and neoplastic tissues have low glycogen levels, they are not stained by Lugol solution [2]. Lugol staining has long been regarded as the gold standard for the detection and delineation of squamous cell carcinoma (SCC) and squamous dysplasia [6]. However, Lugol solution can cause thyrotoxicosis in patients with thyroid disease, iodine hypersensitivity, and retrosternal discomfort [2]. Regarding the avoidance of these side effects, several studies have compared Lugol’s iodine chromoendoscopy and NBI. A recent meta-analysis revealed no significant difference in diagnostic sensitivity between the two methods (88% versus 92%); it also revealed that NBI has a significantly higher specificity than Lugol’s iodine chromoendoscopy (88% versus 82%) [7]. Furthermore, several observational studies reported no significant difference in complete resection rate between the two methods [8, 9].

4. Electronic chromoendoscopy

Electronic chromoendoscopy involves endoscopic imaging technologies that provide detailed contrast enhancement of the mucosal surface and blood vessels in the form of electronic signals that can be analyzed using various image-processing techniques [10, 11]. There are various types of electronic chromoendoscopy, and they include NBI, i-SCAN, and flexible spectral imaging color enhancement (FICE).

4.1 NBI

NBI is an endoscopic optical image enhancement technology based on the penetration properties of light. An NBI filter in front of a xenon arc lamp produces two narrow bands of light with wavelengths of 415 nm and 540 nm [10]. Capillaries in the superficial mucosa are highlighted by the 415-nm-wavelength light band and appear brown. The longer 540-nm-wavelength light band makes deeper-lying veins appear blue-green [11]. Due to an abundance of blood vessels in the submucosal layer, a normal esophagus appears pale green on NBI [12]. Thus, lesions can be observed in great detail as a result of the color contrast effect at the mucosa of the gastroesophageal junction (GEJ) and in cases of early esophageal SCC (ESCC) [11].

4.2 i-SCAN

i-SCAN (Pentax, Tokyo, Japan) is another postprocessing digital contrast technology that consists of three enhancement features: surface enhancement, which sharpens the image; contrast enhancement, where darker (depressed) areas look bluer; and tone enhancement, a form of digital narrowed-spectrum imaging [13]. It was reported in several studies that i-SCAN is superior to white-light endoscopy (WLE) in the detection of reflux esophagitis and dysplasia in BE [14, 15]. However, i-SCAN is a relatively recent technology compared with NBI, and further research is still needed.

4.3 FICE

The FICE system takes an ordinary endoscopic image of different parts of the gastrointestinal mucosa from the video processor and arithmetically processes and estimates it to produce an image of a given dedicated wavelength between 400 and 700 nm. Single-wavelength images are randomly selected and assigned the colors red, green, and blue to build and display virtually enhanced color images [16]. A previous study compared WLE and the FICE system for the diagnosis of BE, but additional research is needed [17].

5. Artificial intelligence (AI)

In this section, understanding of the concepts of AI, machine learning (ML), deep learning (DL), and convolutional neural network (CNN) is essential. AI is the broadest term used in the description of machines that mimic human intelligence [18]. ML is a subfield of AI, and DL is a subfield of ML. ML is divided into supervised learning and unsupervised learning. In supervised learning, labeled datasets are used to train algorithms to classify data or predict outcomes accurately. In contrast, in unsupervised learning, unlabeled datasets are used to train algorithms [19]. In DL, unsupervised learning and neural networks are used. CNN is a type of artificial neural network used in image recognition and processing that is specifically designed to process pixel data [20]. AI is extensively used or studied with regard to the esophagus and will be considered at the end of the discussion of each disease.

6. Esophagitis

Esophagitis refers to inflammation or injury to the esophageal mucosa [21]. The types of esophagitis based on etiology include reflux esophagitis, infectious esophagitis, exfoliative esophagitis, eosinophilic esophagitis (EoE), and pill-induced esophagitis.

6.1 Reflux esophagitis

Gastroesophageal reflux disease (GERD) is a condition in which stomach contents reflux into the esophagus or beyond (e.g., into the oral cavity, larynx, or lungs) causing troublesome symptoms and complications [22]. The extent of mucosal breaks due to erosion or ulceration is the sole determinant of severity grade [23]. Grade A refers to one or more mucosal breaks no longer than 5 mm that do not extend beyond two mucosal folds. Grade B refers to one or more mucosal breaks more than 5 mm long that do not extend beyond two mucosal folds. Grade C refers to one or more mucosal breaks that extend beyond two or more mucosal folds but involve less than 75% of the esophageal circumference. Grade D refers to one or more mucosal breaks that involve at least 75% of the esophageal circumference. Currently, due to lack of interobserver agreement, minimal changes are not included in the GERD Los Angeles (LA) classification [23]. Recently, a DL model that uses CNNs for automatic classification and interpretation of routine GERD LA grades was proposed [24]. However, given that the available data are limited, more studies are needed.

6.2 Candida esophagitis

Esophageal candidiasis is the most common type of infectious esophagitis [25]. Immunocompromised patients are most at risk, and the most common symptoms are odynophagia, dysphagia, and retrosternal pain. Endoscopic examination is the best approach to diagnosing esophageal candidiasis, and multiple white plaques adherent to the mucosa are considered definitively diagnostic of the disease (Figure 2). The most common treatment is systemic and oral administration of fluconazole, an antifungal agent [25].

Figure 2.

Esophageal candidiasis.

6.3 Viral esophagitis

The two most common causes of viral esophagitis are herpes simplex virus (HSV) and cytomegalovirus (CMV). HSV esophagitis ulcers are circumscribed ulcers with raised edges that are described as volcano-like ulcers [26]. CMV esophagitis ulcers are well-demarcated vertical or horizontal linear shallow ulcers that occur in the middle and distal portions of the esophagus [27]. It is sometimes difficult to differentiate between HSV esophagitis and CMV esophagitis because their endoscopic characteristics often overlap [28]. Recently, an ML model for differentiating CMV esophagitis from HSV esophagitis was developed. It was developed based on the analysis of 87 patients with HSV esophagitis and 63 patients with CMV esophagitis using 666 endoscopic images of HSV esophagitis and 416 endoscopic images of CMV esophagitis. The sensitivity and specificity of the model were 100% [28].

6.4 Sloughing (exfoliative) esophagitis

Sloughing esophagitis is characterized by superficial necrotic squamous epithelium and endoscopic plaques or membranes (Figure 3) [29]. The symptoms include dysphagia, odynophagia, nausea, vomiting, abdominal pain, heartburn, chest pain, hematemesis, and obstructive symptoms secondary to the accumulation of casts in the esophageal lumen [30]. The pathogenesis is thought to involve exposure to drugs that cause esophageal damage or autoimmune conditions accompanied by esophageal damage. Such drugs include dabigatran, nonsteroidal anti-inflammatory drugs, bisphosphonates, and iron. The autoimmune conditions include celiac disease, pemphigus vulgaris, bullous pemphigoid, and lupus [30]. Prognosis is usually favorable, and long-term complications are rare. Treatment includes discontinuation of the offending agent and administration of proton-pump inhibitors (PPIs). Steroids may be helpful when a patient has an autoimmune condition [30].

Figure 3.

Sloughing esophagitis.

6.5 EoE

EoE is a chronic immune-mediated inflammatory condition of the esophagus. Its symptoms are mainly related to esophageal dysfunction and include vomiting, dysphagia, and feeding difficulties. Diagnosis of EoE requires endoscopy with biopsy. The endoscopic findings include furrows (i.e., vertical lines in the mucosa), concentric rings, white plaques, edema, and stricture (Figure 4). The American College of Gastroenterology (ACG) recommends a minimum of six biopsies. A finding of 15 or more eosinophils per high-power field in the maximally affected area is required for diagnosis [31]. The treatment options are PPIs, topical corticosteroids, and allergy testing–directed elimination diet. A previous study presented a graphical representation of a suggested management algorithm [32].

Figure 4.

Eosinophilic esophagitis.

6.6 Pill-induced esophagitis

Pill-induced esophagitis may present as erosions, kissing ulcers, and multiple small areas of ulceration with bleeding mainly in the middle third of the esophagus [33]. Treatment of pill-induced esophagitis consists of discontinuation of the offending drug and use of PPIs or sucralfate to hasten esophageal mucosal healing [34].

7. BE and early EAC

BE is a condition characterized by metaplasia of normal esophageal squamous epithelium to specialized columnar epithelium with goblet cells [35]. The ACG guidelines recommend considering BE when the length of the columnar mucosa is at least 1 cm. When BE is suspected, at least eight random biopsy samples should be taken if the BE segment length is <2 cm, and in patients with suspected long-segment BE, four biopsy samples should be taken for every 2 cm of BE segment [36]. Based on the length of salmon-colored mucosa proximal to the GEJ, BE is classified into two groups: short-segment BE and long-segment BE (Figure 5). Long-segment BE is defined as BE with segment length ≥ 3 cm, and short-segment BE is defined as BE with segment length < 3 cm [36]. Screening endoscopy is recommended for patients with chronic GERD symptoms and three or more additional risk factors of BE (e.g., male gender, age > 50 years, white race, tobacco smoking, obesity, and history of BE or EAC in a first-degree relative) [35]. If screening endoscopy does not reveal dysplasia, surveillance endoscopy should be repeated in 3–5 years. Further, a histological grade of “indefinite for dysplasia” should be confirmed by a second pathologist with gastrointestinal expertise, PPI therapy should be initiated, and endoscopic biopsy should be repeated within 6 months [35]. When the histological grade is low-grade dysplasia (LGD), endoscopic mucosal resection or endoscopic submucosal dissection of all visible lesions should be performed, followed by ablation of the remaining BE segment (i.e., endoscopic eradication therapy [EET]) with the goal of complete eradication of intestinal metaplasia (CEIM). Alternatively, surveillance can be performed every 6 months for the first year and annually thereafter [36]. When the histological grade is HGD or intramucosal carcinoma (T1a), EET with the goal of CEIM should be performed. It is recommended to enroll patients with LGD or HGD for surveillance and reflux control after CEIM is achieved [35]. Surveillance at 1 year after CEIM and every 2 years thereafter is recommended for patients with LGD. Surveillance at 3, 6, and 12 months after CEIM and annually thereafter is recommended for patients with HGD or intramucosal carcinoma [35]. Esophagectomy is typically recommended for patients with EAC and submucosal invasion (T1b). Alternatively, EET can be considered for patients with superficial submucosal invasion (sm1, to a depth < 500 μm) and low-risk features such as negative deep margin, well-moderate differentiation, and absence of lymphovascular invasion [35]. Regarding neoplasia detection, the sensitivity and specificity of AI are >90% and > 80%, respectively. Further, regarding neoplasia characterization, the sensitivity and specificity of AI are 90% and 88%, respectively [37].

Figure 5.

Barrett’s esophagus. (a) WLE. (b) NBI.

8. ESCC

ESCC is the most common type of esophageal cancer worldwide; it is especially common in Asia and Africa (Figure 6) [38]. The risk factors for ESCC include long-standing exposure to tobacco and alcohol, achalasia, head and neck squamous cell cancer, tylosis, history of lye ingestion, celiac sprue, and hot liquid ingestion [39]. In addition, the etiological role of human papilloma virus infection is under study [39]. Endoscopic screening should be considered in the presence of risk factors. Infiltration depth prediction is important since it is primarily associated with lymph node metastasis [40]. The Japan Esophageal Society uses a simplified classification of vessel irregularities known as intrapapillary capillary loops (IPCLs) to predict infiltration depth. Type A vessel refers to a normal or abnormal microvessel without severe irregularity, that is, a microvessel with normal epithelium or inflammation and low-grade intraepithelial neoplasia [41]. Abnormal microvessels with severe irregularity or highly dilated abnormal vessels are classified as type B1, B2, or B3. Type B1 vessels have loop-like formations and a predicted invasion depth of epithelium (EP) or lamina propria mucosae (LMP). Type B2 vessels do not have loop-like formations, and their predicted invasion depth is muscularis mucosae or submucosa (SM1). Type B3 vessels have highly dilated vessels and a predicted invasion depth of the submucosa (SM2) or deeper [41]. ESD is recommended for lesions with invasion depth of T1a-EP/T1a-LMP, noncircumferential lesions, and circumferential lesions with lengths ≤5 cm. Furthermore, ESD can be used to remove noncircumferential lesions with invasion depth of T1a-MM/T1b-SM1. Surgery or chemoradiation should be considered when the invasion depth is T1a-EP/T1a-LMP and lateral extension is circumferential with length > 5 cm. It should also be considered when the invasion depth is T1a-MM/T1b-SM1 and lateral extension is circumferential [39]. In a recent study by Everson et al., it was reported that the sensitivity and specificity of AI using CNN for the classification of abnormal IPCL patterns were 89.3% and 98%, respectively [42].

Figure 6.

Esophageal squamous cell carcinoma. (a) WLE, (b) tone enhancement mode with i-scan.

9. Esophageal diverticulum

Esophageal diverticula are a rare condition that causes dysphagia, regurgitation, and chest pain [43]. They are classified into two: pulsion diverticula and traction diverticula. Pulsion diverticula are associated with increased intraluminal pressure, which causes herniation. Zenker’s diverticulum, which is a pulsion-type pharyngoesophageal pseudodiverticulum, is the most common type of esophageal diverticulum (Figure 7) [44]. Surgery can be considered for the management of Zenker’s diverticulum. However, the current first-line treatment involves cutting the entire septum and creating a common cavity between the esophagus and the diverticulum [45]. There are two methods of endoscopic septum division. The first is conventional flexible endoscopic septum division, which entails full-thickness incision of the mucosa, submucosa, and the muscular fibers to create a common cavity between the esophagus and the diverticulum. The second is Zenker’s diverticulum per-oral endoscopic myotomy, which entails minimal mucosal incision to advance the endoscope into the submucosal space of the septum. Complete septotomy is then performed, and the mucosal incision site is securely closed with several endoclips [45].

Figure 7.

Zenker’s diverticulum.

10. Esophageal inlet patch

Esophageal inlet patches (IPs) are well-circumscribed areas of mucosa that are salmon-pink in color, variable in size, and oval-round or even geographically shaped (Figure 8) [46]. Most IPs are located just below the upper esophageal sphincter or in the postcricoid region of the esophagus [46]. Since most IPs present with no symptoms and are located in the upper esophagus, where endoscopists tend to pass the endoscope quickly, it is difficult to identify and observe IPs in detail. However, since adenocarcinomas sometimes arise in IPs, careful observation is necessary [47]. It is recommended that WLE be used first when inserting the endoscope and NBI be used to observe the esophagus up to the pyriform sinus when retracting the endoscope.

Figure 8.

Esophageal inlet patch. (a) WLE. (b) NBI.

11. Esophageal stricture

Esophageal stricture is an abnormal narrowing of the esophageal lumen (Figure 9). It can be benign or malignant. The etiology of benign esophageal stricture includes corrosive substance ingestion, EoE, radiation injury, and drug-induced esophagitis. Treatment includes mechanical or balloon dilation, esophageal stents, or surgical management [48].

Figure 9.

Esophageal stricture: (a) with a bean stuck in the stricture; (b) after bean removal.

12. Esophageal hiatal hernia

Hiatal hernia is a condition in which the upper part of the stomach bulges through an aperture in the diaphragm (Figure 10). There are four anatomical classifications of hiatal hernia: types 1, 2, 3, and 4. Type 1 or sliding hernias are associated with symmetrical ascent of the stomach through the diaphragmatic crus. A patient with type 1 hernia who has reflux symptoms can first undergo PPI therapy with lifestyle modification. In contrast, a patient with symptomatic paraesophageal hernia (types 2, 3, and 4) is at high risk for obstruction, and surgery should be considered for such a patient [49].

Figure 10.

Esophageal hiatal hernia: (a) sliding-type hiatal hernia; (b) paraesophageal hernia (mixed type).

13. Esophageal polyps

13.1 Esophageal squamous papilloma

Esophageal squamous papilloma is a wart-like exophytic mass located in the middle to distal esophagus (Figure 11). Most papillomas are benign, small, and can be easily removed during forceps biopsy. However, owing to the few reported cases of carcinomatous transformation of these lesions, definite removal is necessary if a papilloma bleeds, is unusually large, elicits foreign-body sensation, or shows atypical changes on histological examination [50].

Figure 11.

Esophageal squamous papilloma.

13.2 Sentinel polyp

Esophageal sentinel polyps (or sentinel folds) are inflammatory polyps at the GEJ associated with recurrent GERD (Figure 12) [51]. Although sentinel polyps are benign, biopsy is indicated if a lesion is discovered for the first time or if it changes in size or shape.

Figure 12.

Sentinel polyp.

13.3 Hyperplastic polyp

Hyperplastic polyps are uncommon lesions that most commonly occur at the GEJ (Figure 13) [52]. There are no reported cases of malignant transformation of esophageal hyperplastic polyps [52]. However, when the polyp size is larger than 10 mm, it is difficult to determine if the polyp originated from the GEJ or from the gastric cardia; in such cases, complete removal of the polyp should be considered [53].

Figure 13.

Hyperplastic polyp at the GEJ.

14. Esophageal subepithelial lesions

Subepithelial lesions (SELs) of the gastrointestinal tract are tumors that originate from the muscularis mucosa, submucosa, or muscularis propria [54]. The most common (70–80%) benign esophageal SEL is leiomyoma [55]. However, carcinoid tumors, lymphomas, glomus tumors, and gastrointestinal stromal tumors (GISTs) are malignant or have malignant potential and must be considered [56]. The 2022 European Society of Gastrointestinal Endoscopy (ESGE) guidelines do not recommend WLE or advanced imaging techniques for the characterization of SEL subtypes. Furthermore, the guidelines recommend endoscopic ultrasonography (EUS) as the best tool for the characterization of features of SEL (e.g., size, location, originating layer, echogenicity, shape), but EUS alone cannot distinguish between the types of SEL. Tissue diagnosis is required for SELs with features suggestive of GIST, size >20 mm, high-risk stigmata, or requirement of surgical resection or oncological treatment. The ESGE suggests esophagogastroduodenoscopy (EGD) surveillance at 3–6 months if asymptomatic SELs are found on EGD. EGD is recommended at intervals of 2–3 years for lesions <10 mm and at intervals of 1–2 years for lesions 10–20 mm in size. For asymptomatic unresected SELs >20 mm in size, the ESGE recommends surveillance with EGD plus EUS at 6 months, and then at intervals of 6–12 months [54].

15. Esophageal varix on screening and surveillance

Esophageal varices are dilated submucosal veins of the distal esophagus that connect the portal and systemic circulations (Figure 14) [57]. General rules for describing endoscopic findings of esophageal varix were proposed by the Japan Society for Portal Hypertension [58]. The rules define six main categories: location (L), form (F), color (C), red color (RC) signs, bleeding signs, and mucosal findings. Regarding location, Ls, Lm, and Li stand for Locus superior, Locus medialis, and Locus inferior, respectively. Regarding form, F0 denotes no varicose appearance, F1 denotes straight small-caliber varices, F2 denotes moderately enlarged and beady varices, and F3 denotes markedly enlarged, nodular, or tumor-shaped varices. Regarding color, Cw denotes white varices, Cb denotes blue varices, CwTh denotes thrombosed white varices, and Cb-Th denotes thrombosed blue varices. Regarding RC signs, RWM denotes red wale markings, CRS denotes cherry red spots, HCS denotes hematocystic spots, and Te denotes telangiectasia. Nonselective beta-blockers (e.g., nadolol, propranolol, carvedilol) should be considered if small (≤5 mm) varices with RWM or medium/large (>5 mm) varices are found on screening endoscopy [59].

Figure 14.

Esophageal varix.

Conflict of interest

The authors declare no conflict of interest.