Preface

*Esophageal Surgery - Current Principles and Advances* is a collection of chapters concerning technology innovation in medical practice. It covers a wide range of applications of esophageal surgery in fields of medicine such as radiology, gastroenterology and surgery.

This book is written for healthcare professionals wishing to understand the principles and applications of new technology in esophageal surgery. The material is accessible to anyone, regardless of technical skills. It is suitable as a textbook for undergraduate and postgraduate clinical training. I hope that other experts will be encouraged to contribute to this work through their own experiences. I would like to thank the authors who shared their intellectual and practical expertise and experiences. I also want to thank the staff at IntechOpen, especially Ms. Marica Novakovic and Ms. Jelena Germuth, for their assistance, competence and patience, without which the publication of this book would not have been possible.

I would like to thank my muse, Barbara, for her support every day.

*"Culture is the name for what people are interested in, their thoughts, their models, the books they read and the speeches they hear."*

*- Waller Lippmann*

**Andrea Sanna** Department of General Surgery, Saint Mary of Angels Hospital, Adria, Italy

> Aulss 5 Polesana, Rovigo, Italy

**1**

Section 1

Imaging

Section 1 Imaging

#### **Chapter 1**

## Introductory Chapter: Esophageal Cancer – Current Practice

*Enrico Piva and Andrea Sanna*

#### **1. Introduction**

Esophageal cancer as a part of upper GI cancers represents the VI leading cause of death for cancer worldwide. The overall 5-year survival rate is from 15 to 25% [1].

Histology of esophageal cancers are various; however, the two major histological subtypes are squamous cell carcinoma (SCC) and adenocarcinoma (AC). Differences in epidemiological distribution of these two major subtypes are observed in eastern and western countries: In east Asia and eastern and southern Africa, SCC has higher prevalence; differently from western countries where prevalence of AC is higher, it is continuously increasing [2, 3].

Esophageal cancer's treatments depend on stage at diagnosis and go from endoscopic resections to conversion surgery for metastatic disease.

Multidisciplinary approach and tailored surgery after multimodal treatment have strongly become current standard for esophageal cancer and R0 intended esophagectomy and continue to play a central role, despite high morbidity and mortality related to these procedures [4].

Effectiveness and oncological adequacy of minimally invasive surgical strategies strengthened their role in multimodal treatment.

#### **2. Early stage and endoscopic resection**

Endoscopic resection (ER) for esophageal cancer has become a standard for both AC and SCC confined within lamina propria (≤ stage IB) and with low propensity of lymph node metastasis. Nevertheless, in AC data for esophageal cancer lymph node metastasis propensity showed less consistency [5].

A recent study found that for AC lesion >30 mm propensity for submucosal invasion and lymph node invasion was higher and was defined as relative indication for ER, together with the submucosal layer invasion <200 μm. Endoscopic experience, epidemiology of early cancers in east Asia, and precise and accurate studies in eastern countries lead eastern surgeons to expand indications for ER with good oncological outcomes.

Japan Clinical Oncology Group (JCOG) reported a trial 0508 results for ER followed by CRT in patients with SCC staged Ic and they concluded that their strategy was an adequate and effective alternative for R0 esophagectomy in these patients [6].

#### **3. Squamous cell carcinoma treatment strategy**

Treatment strategies for SCC, because of its lower propensity of hematogenous metastasization and serosa spreading attitude, have developed differently from AC ones, according to evidences.

National Comprehensive Cancer Network (NCCN) Guideline, European Society for Medical Oncology Clinical practice guidelines, and Japanese guidelines consider standard for Esophageal cancer staged cT1-2 N0M0 upfront surgery subordinately for the assessment of adequacy of the patient to elective major surgery. In patients unfit for surgery or not willing to undergo major surgery, definitive CRT should be recommended [7–9].

Treatment for locally advanced resectable SCC has strongly become multimodal and in western country CROSS trial stated a milestone for esophageal cancer treatment. Other scheme for neoadjuvant CT-CRT and adjuvant strategies have been investigated and entered in current practice [9–15].

SCC differently from AC has a specific radiosensitivity and often after neoadjuvant CRT complete pathological response (CPR) has been reported (ypT0N0). The preSANO trial was a prospective multicenter diagnostic cohort study, which aims to establish the accuracy of detection of residual diseases after neoadjuvant CRT. The study showed that endoscopic ultrasonography, bite-on-bite biopsies, and fine needle aspiration (FNA) of lymph nodes were adequate techniques to detect locoregional residue disease together with PET CT for distant metastases. Based on this evidences, a phase III trial (SANO trial) is trying to propose definitive CRT for locally advanced esophageal SCC in patient with complete clinical response (CCR), and this will lead to new approaches for patients unfit for surgery and question the indication for major resection in fit patients as well [16–18].

In patients affected by initially unresectable SCC, conversion surgery has entered in current practice [18].

Resectability of an extended locally advanced disease or oligometastatic disease after neoadjuvant strategy has shown good overall survival (OS) and disease-free survival (DFS) in many different solid tumors' surgery. Although in colorectal surgery conversion therapy is commonly performed, significance of this approach for esophageal cancer is still under debate and lack of strong evidences [19, 20].

#### **4. Adenocarcinoma treatment strategy**

Adenocarcinoma is the prevalent histology in western countries and experiences differ with eastern ones [21].

Often adenocarcinomas concern to esophagus gastric junction EGJ and localization that slightly differs from thoracic and cervical location because of their different propensity of lymph node metastasization in abdominal district. Siewert classification differentiates type I above Z 2 cm above Z line, type II within 2 cm above Z line and 3 cm below it, and type III below 3 cm of Z line. Studies showed that Siewert III lymph node metastasization was more similar to gastric cancer than what Siewert I and II were [22, 23].

These evidences reflect on current multimodal strategy in which CRT plays a central role as in SCC did, but for distal EGJ AD perioperative CT strategy similar to gastric cancer gave marvelous results [10–12, 24–26].

In surgical strategies, these evidences in lymph node metastasis attitude and tropism for peritoneal spreading reflect in needing for mandatory preoperative laparoscopy for peritoneal assessment and accurate abdominal lymphadenectomy strategy.

#### **5. Technique: focus on minimally invasive surgery**

Minimally invasive esophagectomy (MIE) has slowly become standard in current practice after evidences about its safety and oncological adequacy.

Two randomized controlled trial were conducted about MIE. The TIME trial compared MIE versus open esophagectomy (OE) in patients affected by cT1-3, N0-1, M0 esophageal cancer evaluating pulmonary complication surgery related, quality of life (QOL), and hospital length of stay (LOS) [27]. Results showed lower ratio for pulmonary complication in MIE arm and better outcomes in terms of LOS and QOL. 3-year follow-up showed no differences in DFS or OS for OS vs. MIE [28].

The other randomized controlled trial was MIRO trial, which investigated transthoracic open procedure versus hybrid minimally invasive procedure (hMIE laparoscopy and thoracotomy) in patients who underwent subtotal Ivor-Lewis esophagectomy. Complications according to Clavien Dindo grade II or higher were assessed [29]. No differences in survival secondary outcomes and in complications rate between the two groups were assessed.

Currently, a phase III trial compares MIE and OE in ongoing [30].

Another MIE approach described is mediastinoscopy-assisted trans hiatal esophagectomy (MATHE), procedure that avoids single lung ventilation and seems to decrease pulmonary post-operative complications [31].

Robot-assisted surgery is a current practice in surgical oncology worldwide and robot-assisted MIE (RAMIE) has become a standard.

ROBOT trial is the only single-center randomized controlled trial comparing OE and RAMIE with primary endpoint overall complication rate (Clavien Dindo II or Higher). The overall complication rate resulted to be lower in patients underwent RAMIE procedure than OE [32]. RAMIE cost effectiveness is still in debate.

#### **Author details**

Enrico Piva1,2 and Andrea Sanna1,2\*

1 Department of General Surgery, Saint Mary of Angels Hospital, Adria, Italy

2 Aulss 5 Polesana, Rovigo, Italy

\*Address all correspondence to: and\_sanna@yahoo.it

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Annals of Surgical Oncology. 2012;**19**(1):68-74. DOI: 10.1245/s10434-011-2049-9

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[15] Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Japanese Journal of Clinical Oncology. 2013;**43**(7):752-755. DOI: 10.1093/jjco/hyt061

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[20] Terada M, Hara H, Daiko H, et al. Phase III study of tri-modality combination therapy with induction docetaxel plus cisplatin and 5-fluorouracil versus definitive chemoradiotherapy for locally advanced unresectable squamous-cell carcinoma of the thoracic esophagus (JCOG1510: TRIANgLE). Japanese Journal of Clinical Oncology. 2019;**49**(11):1055-1060. DOI: 10.1093/jjco/hyz112

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[23] Mine S, Kurokawa Y, Takeuchi H, et al. Distribution of involved abdominal lymph nodes is correlated with the distance from the esophagogastric junction to the distal end of the tumor in Siewert type II tumors. European Journal of Surgical Oncology. 2015;**41**(10):1348- 1353. DOI: 10.1016/j.ejso.2015.05.004

[24] Zanoni A, Verlato G, Giacopuzzi S, et al. Neoadjuvant concurrent chemoradiotherapy for locally advanced esophageal cancer in a single high-volume center. Annals of Surgical Oncology. 2013;**20**(6):1993- 1999. DOI: 10.1245/s10434-012-2822-4

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[26] Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;**393**(10184):1948-1957. DOI: 10.1016/S0140-6736(18)32557-1

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[32] van der Sluis PC, van der Horst S, May AM, et al. Robot-assisted minimally invasive Thoracolaparoscopic Esophagectomy versus open transthoracic Esophagectomy for Resectable esophageal cancer: A randomized controlled trial. Annals of Surgery. 2019;**269**(4):621-630. DOI: 10.1097/SLA.0000000000003031

#### **Chapter 2**

## Scope of Real Time Fluorescence Imaging in Esophagectomy

*Subramanyeshwar Rao Thammineedi, Srijan Shukla, Nusrath Syed, Ajesh Raj Saksena, Sujit Chyau Patnaik and Pratap Reddy Ramalingam*

#### **Abstract**

Esophagectomy is a challenging surgery that is known to be associated with high rates of morbidity. Anastomotic leaks, pneumonia, conduit necrosis and chyle leaks are the commonly reported complications. Perfusion assessment and tissue injection based fluorescence guided surgery (FGS) are the newer clinical applications of fluorescent dyes. With the advent and integration of real time fluorescence imaging with the existing minimal access platforms, the esophageal surgeon can employ these techniques to potentially improve outcomes. During thoracic dissection, thoracic duct lymphography, fluorescence guided airway visualization, tracheal perfusion assessment and sentinel lymph node biopsy/dissection are the reported clinical applications. In the abdominal dissection, gastroepiploic arcade identification, gastric conduit perfusion assessment and proximal esophagus perfusion assessment have been described. Using the different routes of administration, the same dye can be used for different uses at separate points in a single esophagectomy surgery. The principles and evidence pertaining to these applications have been outlined.

**Keywords:** esophagectomy, indocyanine green, ICG, fluorescence imaging, near infrared, thoracic duct, gastric conduit

#### **1. Introduction**

Real time fluorescence imaging with indocyanine green (ICG) is a promising technology with a potential to resolve many challenges during esophagectomy including the assessment of gastric conduit vascularity, ICG-guided navigation surgery for an adequate lymphadenectomy, detection of sentinel nodes in early stage cancer, defining trachea and bronchial tree and in delineating thoracic duct anatomy and identification of chyle leaks during and after surgery [1]. It is also useful in identifying and safeguarding gastroepiploic arcade vital for gastric conduit creation, especially in obese patients where arcade detection could be challenging. This article provides an overview of the principles of fluorescence imaging, types of fluorescence dyes, indications of fluorescence-guided surgery (FGS) and summarizes the utility of FGS in relation to esophageal surgery.

#### **2. Near-infrared fluorescence- the physics**

Intraoperative fluorescence utilizes the property of specific molecules which absorb light at a particular wavelength and emit light at a longer wavelength [2]. When stimulated by an external light source, these molecules are excited, and the emission occurs at a longer wavelength in the near-infrared range (NIR) (650– 900 nm). The emitted light is captured using a camera equipped with specialized filters, and the visualization of the fluorescence signal is relayed to an external display providing real-time in vivo imaging.

The light emitted in the NIR spectrum cannot be seen by human eyes. The NIR fluorescent cameras selectively capture it. Also, NIR fluorescence has the advantages of low background autofluorescence from blood components (hemoglobin and water) and an excellent signal-to-background ratio, providing clear fluorescence visuals.

#### **3. Fluorescent dyes- the chemistry**

Fluorescein, 5-amino levulinic acid, indocyanine green (ICG), and methylene blue are fluorescent dyes used for in vivo fluorescent imaging. Indocyanine green, small diameter water soluble tricarbocyanine dye, exhibits fluorescence when activated by NIR light within the wavelength of 760 to 780 nm delivered by a near-infrared optical system. On excitation, ICG emits a fluorescence emission between 800 and 850 nm, which the NIR device captures [3]. The depth of tissue visualization varies between 0.5 and 1 cm. When injected intravenously, ICG is tightly bound to the plasma proteins and remains within the intravascular compartment. This property is helpful for angiography assessment of the gastric conduit or tissue perfusion. It rapidly washes out with a short half-life of 150–180 seconds. When injected submucosal or intranodal, ICG is distributed through the lymphatic system. ICG concentrates in the liver and is excreted through the biliary system, which helps delineate the biliary system for fluorescence cholangiography. ICG is relatively safe with a low risk of adverse effects at a dose of 0.1 mg to 0.5 mg/mL/kg for human use [4]. Methylene blue (MB) is a thiazine dye and has also shown to have fluorescent properties. It has an excitation peak of approximately 700 nm with less tissue penetration but more background tissue autofluorescence. It can be administered orally, subcutaneously, or intravenously. MB is excreted through the kidneys and is contraindicated in patients with renal insufficiency [5].

#### **4. Routes of administration- the biology**

The versatility of fluorescent dyes has opened up many interesting clinical applications. The route of administration of the dye determines the drainage pathway of the dye. The resultant highlighted structures can help the surgeon make the intended surgical decisions (**Table 1**). The most commonly used route is the intravenous injection wherein the perfusion of the organ under interest has to be studied. ICG has been successfully studied in assessment of perfusion of anastomotic segments of colon, rectum and esophagus [6]. Because the predominant excretion of ICG happens via the biliary tract, delayed fluorescence imaging performed upto 15 hours after injection allows for cholangiography [7]. When ICG is injected directly into tissues, it gets drained by nearby lymphatic channels to the regional lymph node. This concept


#### **Table 1.**

*Various routes of administration of fluorescence dyes and their clinical applications.*

is utilized in sentinel lymph node biopsy (SLNB). Peritumoral ICG injection has been found to be a suitable alternative to other dyes in breast and endometrial carcinoma [8, 9]. Lymphatic system of retroperitoneum and thoracic duct can be imaged via ICG injection in groin lymph node. This has opened up a new avenue to visualize and manage thoracic duct and chyle leaks [10, 11]. Fluorescein aerosolization has been attempted and fluorescence confirmed on thoracoscopy [12]. Further studies are required to explore the administration of fluorescent dyes via airway.

#### **5. Technology integration**

Recent advances in esophagectomy include wide acceptance of minimal access surgery (MAS) approaches. MAS reduced the major morbidity associated with esophagectomy with equivalent oncological outcomes. With MAS came the advantages of magnification and better identification of surgical anatomy. To improve upon the previous iterations of camera systems, newer cameras have integrated fluorescence imaging capabilities. The first generation fluorescence integrated cameras required the surgeon to switch off white light and the fluorescent structure would get highlighted in a background of darkness. Second generation fluorescence integrated cameras overcame this by adding artificial intelligence to overlay the fluorescent structure over a well-lit background. This enabled interruption free instrumentation and accurate dissection. Portable handheld cameras with integrated fluorescence capabilities are also available now for open surgeries. With these modern adjuncts in the armamentarium, an esophageal surgeon stands at an advantage of having real time information pertaining to various critical steps of an otherwise complex procedure.

The technology has been increasingly utilized for real-time surgical decision-making. Various commercially available equipment for open, laparoscopic, and robotic platforms simultaneously provides high-definition fluorescence and white light images on the same screen. These systems have built-in NIR filters, a camera, and a visual processor for capturing high-definition fluorescent images. The fluorescence and white light modes can be conveniently toggled by clicking a button or using a foot pedal switch (**Table 2**) [5].


**Table 2.**

*Commercially available integrated fluorescence imaging platforms.*

#### **6. Challenges in esophagectomy**

Esophagectomy is a complex surgery requiring the surgeon to master both technical and cognitive skills. MAS approaches have their own learning curves and learning curve associated complications have also been reported [13, 14]. The major challenges for a team managing esophagectomy patients include prevention and management of these postoperative complications. Pneumonia, anastomotic leaks, chylothorax, conduit necrosis are the most often reported complications [15]. Patients who experience major complications tend to have poorer overall survival as well [15]. Predictive factors for anastomotic leaks have been studied and apart from the medical comorbidities of the patient, technique of surgery has also been found to be a significant risk factor [16]. It is generally accepted that ensuring and improving adequate blood supply affects leak rates in esophageal anastomoses [17]. Visual assessment of gastric conduit perfusion is considered inadequate [18]. Fluorescence perfusion assessment offers opportunity to study real time blood supply to the anastomotic segments.

During thoracic dissection in esophagectomy, thoracic duct is a difficult structure to appreciate under white light. As radiation therapy before surgery is being increasingly used for locally advanced tumors, the tissue planes can get fused making identification of thoracic duct even harder. Chylothorax can be very debilitating and may increase length of stay and mortality rates [19]. Fluorescence lymphography is being explored for accurate intraoperative identification of thoracic duct [11, 20]. Newer morphological patterns of thoracic duct previously not described are also being reported [20].

#### **7. Thoracic duct lymphangiography**

Chylothorax after thoracic surgeries is an infrequent postoperative complication. Incidence of chylothorax ranges from 1.4% after transthoracic esophageal resection to 2.4% after transhiatal esophagectomy [21]. Thoracic duct injury is a serious complication after chest surgery and major neck dissections that significantly increases hospital stay, with high in-hospital mortality [22–25]. Chyle leak carries high morbidity up to 38% and mortality as high as 25% [26]*.*

The non-visualization of the thoracic duct with its proximity to the esophagus makes it prone to iatrogenic injury during surgery, leading to chylothorax. The diagnosis is considered in the presence of excessive pleural output and established by biochemical and physical characteristics of the fluid. Intraoperative identification of the thoracic duct can be difficult, especially during reoperation. Because traditional conservative treatment of thoracic duct injury has a high failure rate, intraoperative image guidance is essential for proper surgical management. Presently, *Scope of Real Time Fluorescence Imaging in Esophagectomy DOI: http://dx.doi.org/10.5772/intechopen.107267*

lymphoscintigraphy and lymphangiography are available in preoperative setting to diagnose and recognize the site of thoracic duct injury; however, these procedures cannot accurately guide the surgeon during surgery [27, 28]. Oral administration of heavy cream before surgery is sometimes performed to visualize chyle leak [29].

Real time fluorescence imaging with ICG has the potential to solve all these issues. Thoracic duct NIR fluorescence imaging with ICG has been reported earlier for the recognition of site of chyle leak after esophageal and other thoracic surgeries in form of case reports [11, 30]. Using subcutaneous ICG injection at the inguinal area, Chang et al. identified and ligated chyle leak site through re-sternotomy in a 3-month-old infant with congenital heart disease who had refractory postoperative chylothorax despite multiple line of managements [31]. Kaburagi et al. performed successful mass ligation of thoracic duct at the level of the diaphragmatic crura following ICG injection in mesentery in a case of post esophagectomy chyle leak [32].

Vecchiato et al. reported their experience of minimally invasive esophagectomy with ICG injection in inguinal lymph nodes in 19 patients. The thoracic duct was identified in all patients after a mean of 52.7 minutes from injection time [11]. The protocol followed at the author's surgical unit is as follows. After induction of anesthesia, ICG is injected in groin node with ultrasound guidance. ICG is available as 25 mg powder (Aurogreen; Aurolabs, Madurai, India), which is reconstituted in 10 ml of sterile distilled water. One ml of the solution contains 2.5 mg of ICG. One ml is injected via ultrasound guidance in a groin node, one each on both sides. Generally, the node appears as an oval structure in ultrasound with central echoic and peripheral hypoechoic architecture. A successful administration is noted by tumescence of the node with loss of central hyperechoic architecture. Real time fluorescence lymphography is utilized at the time of thoracic dissection (**Figure 1**). Thoracic duct is visualized and safeguarded in all cases of esophagectomy, unless directly involved by the tumor (**Figure 2**) [1].

#### **Figure 1.**

*Comparison of thoracic duct visualization without and with real time fluorescence lymphography. (A) White light thoracoscopy with esophagus retracted towards surgeon to stretch mesoesophagus to allow for visualization of thoracic duct. (B) Real time fluorescence lymphography turned on, thoracic duct along its course is highlighted.*

#### **Figure 2.**

*Real time fluorescence lymphography depicting thoracic duct involvement by lower third esophageal carcinoma under different modes. (A) Overlay mode. (B) Color segmented fluorescence (CSF) mode.*

#### **8. Fluorescence nebulization for airway visualization**

In locally advanced upper and mid thoracic esophageal cancers, the posterior plane of dissection is limited by the membranous trachea. Bulky subcarinal and hilar lymph nodes can also pose difficulty in dissection over posterior surface of right and left bronchi. The fear of injuring the tracheobronchial membrane makes this part of thoracic dissection in esophagectomy an extremely challenging task. Fluorescence guided airway visualization could be an adjunct in this regard.

Thoracic surgeons have utilized ICG for determining the intersegmental plane in lung segmentectomies [33]. While intravenous ICG injection was studied initially, subsequently endobronchial injection has also been successfully attempted [34]. The authors have applied the same principle by performing nebulization of ICG for early visualization and accurate dissection of posterior membrane of trachea and bronchus in difficult tumors. Using the overlay mode of the NIR camera, esophagus and the lymph nodes can be safely separated from the highlighted membranous trachea and bronchus. **Figure 3** illustrates this technique. Fluorescence nebulization is being tested as a prospective study to standardize the application and evaluate the safety and potential advantages.

#### **Figure 3.**

*Fluorescence nebulization and airway visualization. (A) Middle third esophageal tumor (ESO) with contiguous bulky subcarinal lymph node (VII). Right main bronchus (RMB) is dissected away. Left main bronchus (LMB) remains to be dissected, posterior surface is starting to come into view and is highlighted via fluorescence. (B) Subcarinal lymphadenectomy and ventral dissection of esophagus over LMB is complete.*

#### **9. Sentinel nodal mapping and guided lymphadenectomy**

Real time fluorescence imaging can be used for lymphatic mapping in esophageal cancer to better delineate the lymphatic pathways and to aid nodal dissection. Yuasa et al. determined the feasibility of sentinel lymph node (SLN) detection using intraoperative ICG fluorescence imaging navigated by preoperative computed tomographic lymphography (CTLG) in 20 superficial esophageal cancer patients. Preoperative CTLG localized the number and site of SLNs during computed tomography. Further, SLNs were identified intraoperatively, resulting in successful SLN navigation [35]. Schlottmann et al. and Hachey et al. demonstrated the feasibility of sentinel nodal mapping in patients with esophagogastric junction and mid third esophageal malignancies [36, 37]. Schlottmann et al. identified the pattern of nodal drainage by submucosal injection of 2.5 mg ICG via endoscopy in 4 peritumoral quadrants 15–20 minutes before surgery. Left gastric nodes were the first lymph node station to exhibit fluorescence in 8 out of 9 cases. Hachey et al. utilized ICG: human serum albumin (ICG: HSA) to better delineate nodes with near infrared indocyanine green (NIR-ICG). In order to improve fluorescence-guided sentinel lymph node

biopsy, Kim et al., in an animal model, used a novel macrophage-targeting ICG bound to human serum albumin (ICG:MSA). This ICG:MSA compound when injected via endoscopy into esophageal tissue has provided promising results in sentinel lymph node detection in a porcine model [38].

#### **10. Gastric conduit perfusion assessment**

One of the most feared complications post esophagectomy is anastomotic leak (AL), occurring in 10–30% of patients [39]. While fashioning the gastric conduit, both left gastric and short gastric vessels are usually divided. The conduit solely relies on the right gastroepiploic artery for its blood supply. Inadequate perfusion at the tip of the gastric conduit is one of the most critical factors contributing to anastomotic leak. Conventional assessment techniques of the perfusion and viability of gastric conduit such as visual inspection of the gastric conduit color, warmth, pulsation of the arcade and bleed from the cut edges are considered unreliable. Accurate assessment of perfusion and selecting an appropriate anastomotic site are critical to reduce AL [40]. As a means of evaluating blood flow, indocyanine green (ICG) fluorescence angiography (FA) has recently been introduced to provide real-time assessment of the anastomotic area during esophagectomy [18]. ICG can be used as a vascular contrast agent for assessing perfusion of gastric conduit (**Figure 4**) [5].

A meta-analysis by Slooter et al. reported that ICG significantly decreases anastomotic leaks and graft necrosis after esophagectomy (OR 0.30, 95% CI: 0.14–0.63). The pooled change in management rate due to fluorescence angiography using ICG was 24.55%. Change in management included excision of the poorly perfused area of the gastric conduit and change in site of anastomosis. Despite the change in management, the pooled incidence of anastomotic leak and graft necrosis was as high as 14.08% [41]. Another meta-analysis by Degett et al. reported similar anastomotic leak rate (14%) in patients with esophageal anastomoses after intraoperative ICG fluorescence angiographic assessment [42].

Time to fluorescence is an important parameter which has been studied. The data pertaining to this aspect of the fluorescence angiography is heterogenous.

#### **Figure 4.**

*Real time fluorescence perfusion assessment of gastric conduit. (A-F) fluorescence perfusion assessed at various time intervals after intravenous injection of indocyanine green (ICG) dye.*

Ishige et al. studied different patterns of time to fluorescence intensity curves. They found a "normal" pattern, characterized by a sharp high peak in fluorescence intensity in gastric tubes followed by rapid decline to plateau level, prior to division of perigastric vessels in 6 cases (30%). The other 14 cases showed a "gradual" pattern, characterized by an obtuse and low arterial inflow peak and slow increase in fluorescence intensity over time. However, no anastomotic leak occurred in both groups [43]. Yukaya et al. described three types of curves, normal, outflow delayed and an inflow delayed. Anastomotic leak occurred in 23.1% (3/13) in the normal type, 40% (2/5) in the outflow delayed type and 44.4% (4/9) in the inflow delayed type, with no significant difference among the three types [44]. Koyanagi et al. stratified patients into two groups according to ICG fluorescence flow speed: a simultaneous group with identical speed in gastric conduit wall and the greater curvature vessels, and a delayed group where the ICG fluorescence was slower in the gastric conduit wall in comparison to the greater curvature vessels. They calculated a threshold ICG flow speed of 1.76 cm/s in the gastric conduit predicting anastomotic leak. None of the patients developed anastomotic leak in the simultaneous group, while it occurred in 47% (7/15) patients in the delayed group [45]. Kumagai et al. proposed a 90-second rule wherein all anastomoses were to be reconstructed in the area that showed an enhancement within 90 seconds after initial enhancement at the root of the right gastroepiploic artery [19]. The tip needed revision in 50% (35/70), and in 18 of those 35 patients, a change in anastomotic site was needed. Anastomotic leak occured in 1 out of 70 cases (1.4%) [46]. Slooter et al. reported that the time between ICG injection and enhancement of tip was not significantly prolonged in patients with an anastomotic leak versus no leak (63 vs. 45 seconds) (P = 0.066) and time to fluorescence from base of conduit to the planned anastomosis was significantly increased in patients with a postoperative anastomotic stricture (13 vs. 7 seconds [47].

Nakashima et al. described outcomes of fluorescence angiography assessment of the pedicled omental flap performed to reinforce the esophagogastric anastomosis. Poorly perfused omental tissue was excised on the demarcation line. Anastomotic leak and stricture occurred in 1/38 (2.6%) and 2/38 (5.3%) patients respectively [48]. The importance of proximal esophageal stump revision has been emphasized by Thammineedi et al. where 5 out of 13 patients (38.46%) underwent revision of proximal esophageal stump after ICG assessment [18]. Randomized controlled trials are warranted to prove the exact benefit of ICG fluorescence angiography in reducing anastomotic leaks and strictures in esophagectomy.

#### **11. Future directions**

Fluorescent dyes have been around for more than 40 years [3]. In the past decade interest has grown especially after incorporation of fluorescence capable MAS platforms. Most studies of fluorescence guided surgery have been single center experiences. Multicenter trials with better study designs are needed. International collaborations between societies can lead to standardization of techniques and uniform reporting of outcomes.

#### **Conflict of interest**

The authors declare no conflict of interest.

*Scope of Real Time Fluorescence Imaging in Esophagectomy DOI: http://dx.doi.org/10.5772/intechopen.107267*

#### **Author details**

Subramanyeshwar Rao Thammineedi, Srijan Shukla\*, Nusrath Syed, Ajesh Raj Saksena, Sujit Chyau Patnaik and Pratap Reddy Ramalingam Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India

\*Address all correspondence to: shuklasrajan@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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### **Chapter 3**

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

*Jihwan Ko*

#### **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.

**Keywords:** gastrointestinal endoscope, cancer screening, esophageal disease, esophageal cancer, diagnosis

#### **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.

#### **Figure 1.**

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

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.

#### **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.

*Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

#### **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 *Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

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 protonpump inhibitors (PPIs). Steroids may be helpful when a patient has an autoimmune condition [30].

**Figure 3.** *Sloughing esophagitis.*

*Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

#### **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].

#### **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

**Figure 5.** *Barrett's esophagus. (a) WLE. (b) NBI.*

salmon-colored mucosa proximal to the GEJ, BE is classified into two groups: shortsegment 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].

#### **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

*Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

**Figure 6.** *Esophageal squamous cell carcinoma. (a) WLE, (b) tone enhancement mode with i-scan.*

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].

#### **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].

#### **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

**Figure 8.** *Esophageal inlet patch. (a) WLE. (b) NBI.*

*Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

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.

#### **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 druginduced 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

#### **Figure 10.**

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

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].

### **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].

#### **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.

#### **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

**Figure 11.** *Esophageal squamous papilloma.*

*Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

**Figure 12.** *Sentinel polyp.*

**Figure 13.** *Hyperplastic polyp at the GEJ.*

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].

#### **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.*

*Upper Gastrointestinal Endoscopy for Screening or Surveillance: Complication Avoidance… DOI: http://dx.doi.org/10.5772/intechopen.105831*

#### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Jihwan Ko Baekyang Jeil Internal Medicine Clinic, Busan, South Korea

\*Address all correspondence to: jihwanko65@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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