Advances in gastrointestinal endoscopy: A comprehensive review of innovations in cancer diagnosis and management

Abstract

The field of gastroenterology has experienced revolutionary advances over the past years, as flexible endoscopes have become widely accessible. In addition to enabling faster, less invasive, and more affordable treatment, flexible endoscopes have greatly improved the detection and endoscopic screening of malignancies and prevented many cancer-related deaths. The development and clinical application of new diagnostic endoscopic technologies, such as magnification endoscopy, narrow-band imaging, endoscopic ultrasound with biopsy, and more recently, artificial intelligence enhanced technologies, have made the recognition and detection of various neoplasms and sub-epithelial tumors more possible. This review demonstrates the latest advancements in endoscopic procedures, techniques, and devices applied in the diagnosis and management of gastrointestinal cancer.

Key Words: Endoscopy; Colonoscopy; Endoscopic ultrasound; Cancer diagnosis; Therapeutic endoscopy; Gastroenterology; Endoscopic submucosal dissection

Core Tip: This review comprehensively explores the latest advancements in gastrointestinal (GI) endoscopy, highlighting innovations in diagnostic and therapeutic techniques for GI cancers. Cutting-edge technologies such as magnification endoscopy, narrow-band imaging, endoscopic ultrasound with fine-needle biopsy, and artificial intelligence-enhanced methods are transforming cancer detection, staging, and management. Endoscopic approaches like submucosal dissection and mucosal resection are improving outcomes for premalignant and malignant lesions. These developments underscore the pivotal role of endoscopy in reducing morbidity, mortality, and healthcare costs associated with GI cancers.

INTRODUCTION

The field of gastroenterology has undergone a transformative evolution over the past several decades, driven by remarkable advancements in endoscopic technologies. Endoscopy has not only revolutionized the diagnosis and staging of gastrointestinal (GI) cancers but has also emerged as an indispensable tool in their management. From high-definition imaging to artificial intelligence (AI)-enhanced diagnostics, these innovations have redefined clinical practice, enabling earlier detection, more precise interventions, and improved patient outcomes.

This chapter explores the pivotal role of endoscopy in the diagnosis, staging, and treatment of upper and lower GI malignancies. It delves into cutting-edge techniques such as endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and the integration of novel technologies like narrow-band imaging (NBI) and confocal laser endomicroscopy (CLE). Furthermore, it highlights the expanding role of endoscopic ultrasound (EUS) and its evolution from a diagnostic imaging modality to a tool for therapeutic interventions, including fine-needle biopsy (FNB) and tumor staging.

By bridging the gap between innovation and clinical application, this chapter aims to provide a comprehensive overview of the advancements in endoscopic techniques and their implications for GI oncology. Through the lens of evidence-based practice and emerging trends, the discussion underscores how these technologies are shaping the future of gastroenterology and cancer care.

ENDOSCOPIC ADVANCEMENTS IN GI CANCER DIAGNOSIS AND MANAGEMENT

Upper GI endoscopy

The field of gastroenterology has experienced revolutionary advances over the past fifty years as flexible endoscopes have become widely accessible. In addition to enabling faster, less invasive, and more affordable surgical treatment, flexible endoscopes have greatly improved detection and endoscopic screening of malignancies and prevented many cancer-related deaths. The development and clinical application of new diagnostic endoscopic technologies, such as magnification endoscopy (ME), NBI, EUS with biopsy, and more recently, AI enhanced technologies have made the recognition and detection of various neoplasms and subepithelial tumors more possible.

The gold standard for identifying a variety of upper GI (UGI) cancers is conventional video endoscopy. Video endoscopy has historically been used in conjunction with chromoendoscopy, an intra-procedural staining and dyeing technique, to enhance diagnostic output. High-resolution endoscopy has been made possible by developments in high-definition imaging, which enable closer magnification and more distinct visualization of the mucosa. Methods like NBI serve as a contemporary form of "computerized virtual chromoendoscopy", with lower interobserver variability than traditional chromoendoscopy and potentially comparable, if not superior, diagnostic accuracy. Another type of image-enhancement endoscopy that is receiving a lot of attention is autofluorescence imaging, which depends on identifying variations in light absorption/emission between dysplastic and normal tissue, despite this, its usefulness is currently restricted by a high false-positive rate. Two more recent and promising methods, CLE and endocytoscopy, seek to examine the mucosa at the cellular level in real-time, however more research is required to fully understand their best clinical potential[1-4].

EUS was introduced in the 1980s and since then its role has expanded form a diagnostic imaging method for various GI cancers to EUS-guided fine-needle aspiration (FNA) or FNB for further histopathologic examination and locoregional staging of cancers[1-4].

ROLE OF ESOPHAGOGASTRODUODENOSCOPY AND EUS IN DIAGNOSIS AND STAGING OF UGI CANCERS

Diagnosis of esophageal neoplasms

Esophageal epithelial tumors: (1) Esophageal squamous papilloma (ESP): Benign growth of the esophageal epithelium, the exact etiology is unknown, however it has been linked to human papillomavirus virus. Only 0.45% of patients undergoing endoscopy are incidentally found to have ESP. On endoscopy they are characterized by the triad of wart-like projections, exophytic growth, and surface vessel crossing seen on NBI[5,6].

(2) Adenoma: Esophageal adenomas are a rare entity as the esophagus is lined by squamous epithelium rather than columnar epithelium. However, adenomas may develop in Barrett’s esophagus patients, hence malignant transformation is possible via adenoma-carcinoma sequence. They are usually located in the distal end of the esophagus near the gastroesophageal junction, on endoscopy they appear as sessile or pedunculated polyps, they may be nodular or lobulated. Biopsy is crucial to assess malignant status[5].

(3) Inflammatory fibroid polyp: Also known as inflammatory pseudo polyp or eosinophilic granuloma. Inflammatory fibroid polyps are benign growths that are mostly found in the stomach, the esophagus is a rare location. They are sub-mucosal based polypoid lesions with perivascular fibroblastic proliferation. Endoscopic findings include a sessile or pedunculated polyp usually located in the distal end of the esophagus near the gastro esophageal junction, Diagnosis is confirmed via biopsy showing concentric fibroblastic proliferation with thin-walled blood vessels[5-8].

(4) Leukoplakia: Epidermal metaplasia that involves hyperkeratosis, epithelial dysplasia and occasionally carcinoma, it rarely involves the esophagus and is usually found in the oral cavity. Endoscopic appearance includes a slightly elevated whitish plaque that cannot be rubbed off, it may be translucent, or cobble stone in texture with tiny nodules. Endoscopic surveillance and resection are recommended due to malignant potential[5,6].

(5) Glycogenic acanthosis: Benign condition of unknown etiology. It consists of hyperplastic squamous epithelium with abundant cytoplasmic collagen. It’s a degenerative condition incidentally found on endoscopy with no malignant potential. Endoscopic features include small whitish plaques, biopsy shows epithelial cells rich in glycogen[5,6].

(6) Barrett’s Esophagus: Pre-malignant lesion characterized by esophageal squamous epithelium metaplasia into columnar epithelium. It develops as a result of repeated exposure of the esophageal epithelium to refluxed acid from the stomach in the setting of gastroesophageal reflux disease (GERD). Gross endoscopic picture of Barret includes salmon-pink tongue-like projections at the gastroesophageal junction. Biopsy reveals columnar metaplasia and goblet cells. Due to the substantial risk of malignant transformation into esophageal adenocarcinoma surveillance of Barrett is crucial[2,3,5,6,9].

(7) Esophageal squamous cell carcinoma: The most common form of esophageal cancer worldwide. It is the seventh-most common cancer and sixth-most common cause of cancer-related death worldwide. Two of the major risk factors for esophageal squamous cell carcinoma (ESCC) are smoking and alcohol consumption. Due to the high burden of the disease, early detection and treatment of ESCC is of high importance. ESCC arises in the upper and middle third of the esophagus, and can appear as a mass, nodule, stricture, depression, ulceration, or subtle irregularity in the mucosa. White-light endoscopy (WLE) is the standard modality of diagnosis, however it has some limitations especially in early ESCC when the features are subtle. Image-enhanced endoscopy, including dye-based chromoendoscopy and virtual chromoendoscopy and NBI with or without ME is a novel diagnostic technique that has helped detection of tumors and evaluation of depth of invasion. Chromoendoscopy utilizes dyes such as lugol’s iodine, acetic acid, and methylene blue and indigo carmine to enhance mucosal structural details and distinguish abnormal mucosa from normal mucosa. Virtual Chromoendoscopy utilizes hardware to obtain a detailed and enhanced image of the lesion, techniques include NBI with or without ME, and software-based techniques such as i-SCAN and flexible spectral imaging color enhancement (FICE), most recently introduced techniques include blue laser imaging (BLI) and light color imaging. One novel method that has been increasingly prevalent in diagnosing esophageal cancer is AI, convolutional neural networks (CNNs) and deep learning (DL) have made breakthroughs in early detection of esophageal cancer. AI assisted diagnostic techniques achieve the functions of lesion recognition, real-time marking, and analysis of the lesion. EUS is also increasingly used for staging of the tumor and evaluation of regional lymph nodes involvement. Endoscopy with biopsy yields the most diagnosis of ESCC, with biopsy showing nests of malignant keratinocytes and keratin pearls[2,3,5,6].

(8) Esophageal adenocarcinoma: The most common form of esophageal cancer in western countries and the second most common form of esophageal cancer worldwide. GERD is a strong risk factor for EAC, Barret esophagus is the only confirmed pre-malignant lesion for EAC. Another strong risk factor for EAC is obesity, smoking is also a risk factor for EAC though in a lower rate than ESCC, and unlike ESCC alcohol consumption has no role in EAC. Diagnosis of EAC is essentially the same as ESCC as both lesions constitute esophageal cancer, only difference is EAC biopsy shows irregular, malignant glands with luminal mucin production and signet ring cells[5,6].

And (9) Esophageal melanoma: Primary esophageal melanoma is a rare aggressive tumor with early metastasis and a very bad prognosis. It mainly affects men over 60 years old and involves the middle and lower third of the esophagus. Endoscopic features of the tumor include a pigmented non ulcerated tumor, though amelanotic variant of the tumor exists. Satellite lesions occur a few centimeters around the primary tumor due to intramural metastasis. EUS can be used to assess the lymph node involvement but since the tumor is very aggressive and distant and lymph node metastasis are common on presentation, fluorodeoxyglucose-positron emission tomography is currently the most accepted method for metastasis detection[5,6].

Esophageal subepithelial tumors: (1) Granular cell tumor: Benign tumor that is rarely found in the GI tract, the most common site of GI involvement is the esophagus. It has a neural derivation and arises from Schwan cells. The endoscopic appearance of the tumor includes a solitary yellowish submucosal mass that is usually located at the distal end of the esophagus[5,6,10].

(2) Leiomyoma: The most common benign esophageal tumor, and the most common esophageal mesenchymal tumor. It originates from the muscularis propria and is commonly located in the middle or distal esophagus. Endoscopically it appears as a submucosal solitary or multiple masses with overlaying normal mucosa. EUS is the modality of choice to diagnose leiomyoma, and it shows a round hyperechoic lesion arising from the muscularis propria[5,6].

(3) Fibrovascular polyp: Rare benign tumor-like structures almost exclusively found in the cervical esophagus. They occur as a result of dragging of the loose submucosal tissue of the cervical esophagus by the esophageal peristalsis and consist of adipose cells, stroma, and blood vessels covered by normal epithelium. On endoscopy they appear as pedunculated polyps that are always attached to the cervical esophagus by a pedicle. EUS is recommended before excision of large polyps to detect the presence of large blood vessels[5,6].

(4) Hamartoma: Rare esophageal polyps that are endoscopically indistinguishable from fibrovascular polyps, however hamartomas are much less common and histologically they may contain different types of tissues like bone, cartilage, etc. Rarely, multiple esophageal hamartomas can be found in patients with Cowden’s disease[5,6].

(5) Lipoma: The esophagus is the least common site of GI lipoma. Endoscopy shows raised yellowish nodules in the proximal esophagus with pillowing or indentation with palpation. EUS shows a hyperechoic, homogeneous lesion with smooth surface[5,6,11].

(6) Hemangioma: Rare vascular malformations of the esophagus. Rarely, multiple esophageal hemangiomas may be found in Osler-Weber-Rendu disease. There are two types of esophageal hemangiomas: Cavernous and capillary and most lesions are of the cavernous type. Endoscopically, they appear as blue- to red-colored submucosal nodules that blanch with compression[5,6].

(7) GI stromal tumor (GIST): The most common mesenchymal tumor of the GI tract, only 1%-3% of cases occur in the esophagus. Endoscopically they appear as solitary submucosal masses in the distal esophagus. EUS is the modality of choice for diagnosis of esophageal GIST and shows hypoechoic heterogenous lesions, it can also help predict malignant potential[5,6].

(8) Lymphoma: Esophageal lymphoma can be primary or secondary with primary lymphoma being the less common accounting for only 1% of esophageal malignancies. Esophageal lymphomas can be Hodgkin’s or non-Hodgkin's lymphoma (NHL). Diffuse large B cell lymphoma (DLBCL) is the most common subtype of NHL and has been associated with immunosuppressive states such as AIDS. Few cases have been reported and the endoscopic picture varies from submucosal nodules to ulcers to masses. EUS-FNA aids in the diagnosis and staging of the tumor[5,6].

And (9) Sarcoma: Esophageal sarcoma encompasses leiomyosarcomas, GISTs, rhabdomyosarcoma, fibrosarcoma, liposarcoma, fibrous histiocytoma, Kaposi’s sarcoma, and choriocarcinoma. Leiomysarcoma is the most common type and on endoscopy they appear as polypoid or infiltrative lesions. EUS-FNA is helpful in diagnosis and staging[5,6].

Diagnosis of gastric neoplasms

Gastric epithelial tumors: (1) Adenoma: There are four general types of gastric adenoma, the intestine type, foveolar type, pyloric gland type, and oxyntic type. On endoscopy they can be flat or polypoid and are usually solitary, occurring mostly in the antrum, but pyloric and oxyntic types can occur in the fundus and cardia. Malignant potential depends on the size of the lesion, lesions more than 2 cm in size have almost 50% chance of turning malignant. ME with NBI and enhanced ME with acetic acid instillation can be used to assess malignant potential, irregular borders and microvascular pattern suggest malignant transformation into early adenocarcinoma. WLE can also help identify malignant transformation via color change of the lesion from pale to red under the endoscopy[12,13].

(2) Adenocarcinoma: The most common histological type of gastric cancer accounting for 95% of all gastric malignancies. It ranks as the third most common cause of cancer-related fatalities globally. Endoscopic screening lowers the death rate from gastric cancer, as evidenced by several case-control studies from Japan and South Korea that found that subjects who had gastric endoscopic examinations had a significantly lower odds ratio for dying from the disease than those who did not[13].

Gastric adenocarcinoma can be divided into two types according to location, Cardia (proximal) adenocarcinoma, and non- cardia (distal) adenocarcinoma. On endoscopy, the lesions may be elevated, flat, or depressed. According to Borman’s classification of macroscopically large gastric tumors, adenocarcinoma can be divided into polypoid (type I), fungating (type II), ulcerated (type III), and infiltrative (type IV)[13,14]

Another entity is early gastric cancer (EGC) which is defined as invasive gastric cancer limited to the mucosa or submucosa, regardless of lymph node metastasis. The Paris classification was developed to categorize superficial lesions based on their morphology, lesions classified as Paris classification 0-I are polypoid lesions and can be sessile (0-Is), semi-pedunculated (0-Isp), or pedunculated (0-Ip). 0-I lesions have a rough surface with granular or lobulated appearance and are typically bigger in size than benign polyps. Flat lesions (0-II) can either be slightly elevated (0-IIa), at mucosal level (0-IIb), or slightly depressed (0-IIc), while excavated or ulcerative lesions fall under Paris classification (0-III). The hardest of these to identify are the 0-IIb lesions, which might be confused with atrophic gastritis. low rate of lymph node metastasis[15].

Endoscopy is the gold standard for screening and diagnosis of gastric cancer, it allows visualization, staging and biopsy of the lesion. Regarding EGC, determining the depth of invasion is crucial, conventional WLE is the most popular method for determining the depth of invasion. Cancer invasion deeper than 500 μm from the submucosa is indicated on WLE by tumor size ≥ 30 mm, irregular surface, marked hyperemia, marginal elevation, non-extension sign, and submucosal tumor-like raised margins. EUS can help optimize tumor staging when combined with endoscopy and radiologic modalities by offering details regarding the depth of tumor invasion and the degree of peri-gastric lymphadenopathy[13,14,16-19].

(3) Oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type: Extremely rare type of gastric adenocarcinoma, it’s benign in nature and according to World Health Organization classification it is called an oxyntic gland adenoma when it’s limited to the mucosa, if infiltration of the submucosa occurs, it's termed gastric adenocarcinoma of the fundic gland type (GAFG). On endoscopy, they mimic fundic gland polyps or gastric neuroendocrine tumors (NETs) as they are found in the fundus, cardia, and upper third of the body of the stomach, and originate from deeper parts of the mucosa. The most frequent endoscopic findings of oxyntic gland adenoma/GAFG are whitish color, dilated branching vessels, submucosal tumor shape with normal background mucosa without atrophic changes[13].

Gastric subepithelial tumors: (1) Inflammatory fibroid polyp: Rare benign polypoid tumor arising from the submucosa. It’s characterized by proliferation of highly vascular fibrous tissue and infiltration by different inflammatory cells. On endoscopy it usually appears as a solitary, sessile or pedunculated intraluminal polyp mostly located at the gastric antrum. EUS shows an irregular, hypoechoic lesion with heterogeneous echotexture and diffuse margins arising from the 2^nd layer of gastric wall[7,8,13].

(2) Granular cell tumor: Generally benign soft tissue tumor arising from schwann cells. On endoscopy it appears as a yellowish lesion with intact mucosa. On EUS it appears as hypoechoic, homogeneous, round lesion with fine margins[10,13].

(3) NET: Originates from the submucosa and is derived from the enterochromaffin-like cells (ECL cells). The most common type of NETs is carcinoid tumor. On endoscopy it can be sessile or polypoid, small, rounded, with dilated vessels and central erythematous depressions or ulcerations. EUS shows hypo- or isoechoic lesions with smooth margins arising from the submucosa[13].

(4) Leiomyoma: Benign submucosal tumor arising from muscularis mucosa and sometimes from muscularis propria. Endoscopy usually shows a submucosal mass with Schindler's sign (tenting and loss of gastric folds as mucosa is stretched over the submucosal mass). EUS distinguishes leiomyoma from more sinister entities such as GIST, it shows a round, homogeneous, hyperechoic lesion arising from the 2^nd or 4^th layer of the gastric wall[13].

(5) Lipoma: Small, benign tumors. They are usually asymptomatic but rarely can ulcerate and bleed. Endoscopic findings usually consist of a yellowish sessile or pedunculated submucosal mass with smooth covering mucosa, if the covering mucosa is thick, the lesion might not appear yellowish, occasionally lipomas may be lobulated or ulcerated. Endoscopic signs specific to lipoma include; The “cushion” sign demonstrates the spongy nature of the mass when indented, the “naked fat” sign is produced after taking multiple biopsies the overlying mucosa when fat protrudes from the mass, and the “tenting” sign which entails grasping the mucosa and pulling or “tenting” it away from the underlying mass. EUS features include a hyperechoic, homogeneous, round submucosal mass[11,13].

(6) Schwannoma: Rare mesenchymal tumors arising from the nerve plexus in the gut wall. On endoscopy they appear as submucosal masses with or without central ulceration. They can be evaluated by contrast-enhanced harmonic EUS, they usually appear as hypoechoic, exophytic heterogenous enhancements on EUS[13].

(7) GIST: The most common mesenchymal tumors of the GI tract. They originate from the 4^th layer of the stomach wall (Muscularis propria) from pluripotential mesenchymal stem cell programmed to differentiate into the interstitial cell of Cajal. The stomach is the most common site of GIST, followed by the small intestine, colon and rectum, and esophagus. They are typically present as solitary lesions, but in pediatric population they may appear as multiple lesions. They are mainly located in the gastric body 70%, followed by cardia and fundus 15% and gastric antrum 15%. Endoscopic features include a smooth, firm, yellowish submucosal mass that may or may not be associated with ulceration due to pressure necrosis. Diagnosis is usually confirmed by EUS where the tumors appear as hypoechoic, round or irregular heterogenous lesions with cystic spaces, they are surrounded by a marginal halo and usually associated with lymphadenopathy. EUS-FNB is used to confirm the diagnosis with high yield of approximately 86%[13,20].

And (8) Gastric lymphoma: Rare indolent tumors that respond well to treatment. The stomach is the most common site of GI lymphoma, it may be the primary site of lymphoma or be involved as a part of systemic disease. The majority of gastric lymphomas (> 95%) are NHL, mostly B-cell type. The rest are Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, DLBCL, with much less common occurrences of mantle cell lymphoma and follicular lymphoma. The gold standard for diagnosis is esophagogastroduodenoscopy (EGD), on endoscopy gastric lymphomas appear in a wide spectrum of patterns, they may be localized or diffuse. They can appear as nodules, polypoid or exophytic masses or as submucosal tumors. Another appearance of lymphoma is localized or diffuse thickening of the gastric folds, cobble-stone mucosa, or erosions and ulcerations. The endoscopic findings usually involve the distal part of the stomach. Deep endoscopic biopsy is usually implemented rather than the superficial biopsy, as the superficial biopsy might yield no diagnosis. Biopsy is usually obtained via endoscopic snare technique, jumbo forceps, or mucosal resection. EUS is used to evaluate the depth of invasion and the involvement of local lymph nodes via EUS-FNA[13,21].

MANAGEMENT OF MALIGNANT, PREMALIGNANT, AND DYSPLASTIC LESIONS OF THE ESOPHAGUS, STOMACH, AND DUODENUM

ESD

ESD is a well-recognized technique of endoscopic resection first described in 1988 by Hirao et al[22]. It allows for en bloc margin-negative curative removal of superficial GI neoplasms, thus eliminating the need for invasive surgery and preserving the affected organ[22].

Method: The technique is achieved in a step-wise manner and involves: (1) Marking the perimeter of the lesion with cautery; (2) Submucosal injection of a lifting agent (such as normal saline, hypertonic saline, dextrose water, Hydroxyethyl starch, Hydroxypropyl methylcellulose, Hyaluronic acid, and Eleview) around the perimeter of the lesion; (3) Incision of the mucosa and cutting around the lesion using an electrosurgical knife; (4) The submucosa is injected and dissected using an electrosurgical knife in a free-hand manner until the lesion is completely resected; and (5) Bleeding at any point is managed via cleaning with waterjet, clamping with hemostatic forceps, hemostatic agents such as polyglycolic acid sheets, fibrin glue, and PuraStat, and electrocautery of blood vessels via electrosurgical knife[23,24].

Indications: (1) Barrett’s esophagus: Current guidelines support endoscopic resection as treatment for visible changes of Barrett’s esophagus. Both EMR and ESD can be used, however EMR is considered the first line treatment of Barrett’s esophagus. ESD is advised for Barrett’s esophagus in the following conditions, high grade dysplasia (HGD) to moderately (G1 or G2) differentiated T1a (m1-m3) lesions equal to or more than 15 mm (not amenable to en bloc resection by EMR), patients with Barrett’s esophagus and the following features: Large or bulky area of nodularity, equivocal preprocedural histology, intramucosal carcinoma, suspected superficial submucosal invasion, recurrent dysplasia, and EMR specimen showing invasive carcinoma with positive margins[25-27].

(2) ESCC: Since ESCC has a higher risk of lymph node metastasis at early stage, the need for accurate histological evaluation is of high importance. Hence the goal should always be en bloc resection with ESD as first-line treatment. ESD has shown higher rates of en bloc, R0 curative resection and lower rates of recurrence than EMR.

European guidelines support the use of ESD for HGD to well (G1) to moderately (G2) differentiated and Paris 0-II lesions.

Japanese Esophageal Society guidelines divide the indications of ESD into absolute indications (T1a esophageal cancer involving the epithelium or lamina propria, occupying < 2/3 of the lumen of the esophagus), and relative indications (Esophageal cancer involving the muscularis mucosa or < 200 μm invasion of the submucosa)[25-29].

And (3) Stomach: EGC is well established candidate for ESD. United States National Comprehensive Cancer Network discusses the role of ESD for treating patients with superficial gastric cancer in their guideline on gastric cancer.

According to the Japanese Gastric Cancer Association guidelines, the absolute indications for ESD use for EGC are mucosal adenocarcinoma (and lesions with HGD), intestinal type, G1 or G2 differentiation, size ≤ 2 cm with no ulceration, since this group of patients have a negligible risk of lymph node metastasis. The expanded indications include[25-30] (Table 1).

Table 1 The expanded indications.

Histological type	Differentiation grade	Size	Ulceration	Invasion
Intestinal adenocarcinoma	G1 or G2	Any size	Without ulceration	No submucosal invasion
Intestinal adenocarcinoma	G1 or G2	Not specified	Not specified	Submucosal invasion < 500 μm
Intestinal adenocarcinoma	G1 or G2	≤ 3 cm	With ulceration	No submucosal invasion
Diffuse adenocarcinoma	G3 or G4	≤ 2 cm	Without ulceration	No submucosal invasion

EMR

EMR is a specialized technique developed to remove superficial GI tract lesions safely and effectively. It was pioneered in Japan for management of EGC, ang gained popularity since the development of strip biopsy method in 1984. EMR allows for separation of the lesion and surrounding mucosa from the underlying submucosa and then removal of the lesion either en bloc or in a piecemeal method[31,32].

Method: EMR procedures can be divided into suck and cut (suction) or lift and cut (non-suction) techniques. The left and cut technique requires the submucosal injection of a lifting agent to separate the lesion of the underlying muscle layer. The suction method, often used in Barrett’s dysplasia entails the use of a multiband mucosectomy device without submucosal injection where a pseudopolyp is formed using a band and then resected with a snare. During cap- assisted EMR submucosal injection is carried out; the lesion is then sucked into the cap and removed using a pre-looped snare. At the moment, the lift and cut method is the most applied.

There are multiple methods to perform EMR, however the methods follow the same general steps: (1) The lesion is located endoscopically with white light, NBI and dye-based chromoendoscopy; (2) The borders of the lesion are marked with a snare tip or argon plasma coagulation (APC); and (3) All methods utilize snare resection with or without injection, suction banding, cap etc[31,32]. Depending on the size of the lesion, it may need to be in a piecemeal manner or en bloc.

Piecemeal EMR is used for lesions larger than 2 cm, it involves injection of a lifting agent, 1-3 snare extensions and inspection of the mucosal defect. Resection should start at one edge of the lesion and include a 2 to 3 mm margin of normal mucosa using the edge of the advancing mucosal defect as a convenient step for the next snare placement and the mucosal defect is then washed with fluid jet. Piecemeal EMR is considered a risk factor for polyp recurrence especially in colorectal polyps[33].

En bloc EMR is appropriate for lesions up to 20-25 mm, it involves injection of a lifting agent and elevation of the lesion. One the lesion is sufficiently elevated making sure the resection is not the submucosal plane it is then surrounded entirely by the snare and removed completely. En block EMR is associated with lower recurrence rates than piecemeal EMR[33].

Types of EMR: (1) Conventional (injection-assisted)/hot EMR: Conventional EMR entails injecting a lifting agent into the submucosa in order to elevate the lesion from the underlying musclaris propria. Submucosal injections are performed using different solutions. The most commonly utilized agent is normal saline; however, it is absorbed quickly. Other agents such sodium hyaluronate, 50% dextrose, 4% succinylated gelatine, hypertonic saline, etc., are frequently employed to solve this issue. An injection needle is used to administer injections at one or more locations surrounding the lesion. After elevation of the lesion. It is then resected with a snare. Depending on the size of the lesion, it may need to be removed in several pieces or all in one. To reduce the possibility of residual lesion tissue, piecemeal resection involves pivoting the snare along the excised area's edge and resecting the remaining lesion in an overlapping manner and repeating these steps until the entire lesion is excised. Piecemeal excision of a lesion should result in ablated, normal-appearing tissue at the lateral edges of the resection bed. Either APC or snare tip soft coagulation can be used to accomplish this[31,32]; and (2) Cold EMR: The use of electrocautery in hot EMR can cause some adverse events such as bleeding or perforation. The cold EMR approach has been developed to alleviate these events. The basic procedures for cold snare EMR are the same as for hot EMR, but instead of using electrocautery to resect the lesion, a smaller, stiffer snare with a thin cutting wire is frequently employed[31,32].

Indications: Esophagus: Barrett esophagus with dysplasia and early adenocarcinoma: EMR is considered the first line treatment of Barrett’s esophagus with HGD, it allows for accurate staging of the lesion and is considered to be therapeutic and curative when R0 resection is achieved. EMR is considered definitive therapy when: (1) The lesion is well-to-moderately differentiated; (2) The lesion is limited to the mucosal layer; (3) It is ≤ 2 cm; and (4) Has no lymph vascular invasion. low-risk submucosal invasion (T1sm1) can also be considered for endoscopic therapy[27,28].

Squamous cell carcinoma: EMR can be used in lesions with the following characteristics. (1) Lesion < 2 cm; (2) Limited to esophageal mucosa (corresponding to stage T1a); and (3) Involve less than one third of the esophageal circumference[27,28].

Stomach: EMR is widely used for treatment of EGC as an alternative to surgery in Japan. Gastric lesions are removed en bloc via EMR, and the main features of EGC that indicate EMR are: (1) Elevated lesions < 2 cm in size; (2) Depressed lesions less than 1 cm in size without ulceration; (3) Well or moderately differentiated adenocarcinoma of intestinal type; and (4) Absence of lymph node metastasis[27,28].

Duodenum: EMR can be used to remove peri-ampullary or duodenal adenomas, neuro-endocrine tumors and subepithelial stromal tumors. Endoscopic snare papillectomy is increasingly performed with curative intent for benign ampullary lesions. However, available evidence suggests that duodenal EMR and ESD may be associated with a substantial rate of complications, particularly in the treatment of submucosal lesions[27,28].

Endoscopic clipping and suturing

Over the past 15 years, endoscopic clips and suturing devices have advanced significantly, enabling their use in a broad range of procedures such as closing perforations, leaks, fistulas, mucosal defects after resections, and even in anti-reflux and weight loss treatments. These technological advancements in endoscopy have led to innovative approaches in managing a variety of esophageal and foregut conditions. Endoscopic suturing techniques include devices like through-the-scope and over-the-scope clips (OTSC), the endoscopic suturing OverStitch system, and the through-the-scope suturing X-Tack device.

Through the scope clips: Through the scope clip use was first described over 30 years ago, and since then, the variety and capabilities of modern clips have grown exponentially enabling control of GI bleeding and the closure of mucosal injuries and full-thickness defects.

These clips can be highly effective as a standalone treatment for hemostasis, offering advantages over injections or thermal coagulation. Their compact size allows for excellent visualization and field exposure, most current through-the-scope clips are compatible with endoscopes featuring a 2.8 mm working channel, which is standard for the majority of diagnostic endoscopes on the market.

Some of through the scope clips available on the market are, Resolution 360 (Boston Scientific, Marlborough, MA, United States); Instinct (Cook Medical, Bloomington, IN, United States); Dura Clip 11 mm (ConMed, Utica, NY, United States); Quick Clip Pro (Olympus America, Center Valley, PA, United States); and SureClip 16 mm (Microtech, Ann Arbor, MI, United States)[34,35].

Over the scope clips: The over the scope clip system includes an OTSC, an applicator cap, a hand wheel, and a twin or anchor type grasper. The clip is pre-mounted on the applicator cap and deployed using the hand wheel. It is constructed from a nitinol alloy, which has elasticity and shape memory, allowing it to return to its original form once released on the tissue. The clip's teeth can suture the targeted lesion to full thickness. To accommodate various lesion sizes, the OTSC comes in three sizes: 11, 12, and 14 mm. Additionally, there are three claw shapes designed for different purposes: A blunt atraumatic type (a type) used for controlling bleeding, a pointed traumatic type (t type) used to close fistulas, perforations, and a special type for gastric wall closure (gc type). The Ovesco Clip (Ovesco Endoscopy AG, Tubingen, Germany) is an over-the-scope nitinol clip, known as a “bear trap” or “bear claw” for its characteristic appearance[36].

OverStitch endoscopic suturing system: The OverStitch Endoscopic Suturing System (Apollo Endosurgery, Austin, TX, United States) was developed in 2009, however it was not Food and Drug Administration (FDA) approved till 2010. In 2011 an updated version that was compatible exclusively with double-channel Olympus endoscopes was released. In 2018 the OverStitch SX was introduced, enabling use with single-channel endoscopes and making it compatible with all four major commercial platforms (Olympus, Pentax, Fuji, and Storz). Although it is more expensive and time-intensive compared to through-the-scope or OTSC, the OverStitch system allows for traditional surgical suturing, which may offer superior closure for larger or irregularly shaped defects.

The device consists of several key components, including an end cap that attaches to the end of the scope, a needle driver handle, an anchor exchange catheter, and a tissue retraction helix device, which helps in bringing the tissue together. The original OverStitch system is mounted on the distal end of a double-channel therapeutic endoscope, while the OverStitch SX works with single-channel endoscopes.

The suture is first loaded onto the exchange catheter, which is then passed through the operating channel and handed off to the needle driver. The helix device anchors to the tissue, retracting it into position. By closing the needle driver handle, the anchor and suture are pushed through the tissue. Next, the anchor exchange catheter is advanced over the anchor and secured. After the anchor is locked in place, the catheter is retracted, and the tissue is released from the helix device. Releasing the needle driver handle leaves a full-thickness suture. This process can be repeated for additional closure using either interrupted or continuous sutures. To finalize the closure, the anchor exchange catheter is released, disengaging the anchor. The cinch catheter is then advanced, and the suture is tightened to seal the defect. The cinch is deployed, securing the suture in place, and then the suture is cut. The device allows for multiple reloads without needing to remove the endoscope[34,37].

X-Tack: The X-Tack (Apollo Endosurgery, Austin, TX, United States) is a recently introduced through-the-scope suturing tool that allows for nearly surgical-quality closure of tissue defects through the endoscope channel. The device features helical coil tissue tacks pre-loaded on a suture, which can be applied along the edges of resected tissue and tightened to bring the tissue back together. The key advantages of the X-Tack are its ability to close defects in areas that are difficult to access with larger devices and the convenience of being ready for use immediately, without needing to remove the endoscope to install the suturing tool[34].

Clinical applications of the endoscopic clipping and suturing devices

Acute full-thickness GI defects: Acute defects can occur iatrogenically, such as perforations during endoscopic procedures, or spontaneously in cases like malignancies, ulcers, or Boerhaave syndrome. They can also be caused by trauma from foreign objects, blunt force, or penetrating injuries. Endoscopic repair of acute full-thickness defects can be carried out using OTSC and through-the-scope clips. The 90% successful closure rate of acute defects was achieved with OTSC in a study reviewing 24 publications[38]. Multiple case reports have reported 100% success rate of closure was reported with through-the-scope clips in smaller perforations less than 10 mm[39-41].

Non acute full-thickness GI defects: Non acute full-thickness GI defects result from leaks, which can be caused by anastomotic breakdown, infections, or inflammation. Over time these leaks may form epithelialized tracts, leading to fistulas. Endoscopic suturing techniques have advanced the minimally invasive treatment of leaks and fistulas, allowing for surgical-like closure of defects via an endoscopic approach. The use of the OverStitch device in managing UGI leaks showed a 100% success rate for those who had no prior attempts at leak management, while in cases with previous endoscopic treatments, the procedure was unsuccessful, necessitating further interventions[42]. Fistula closure using the OverStitch device demonstrated 100% initial success rate, with 30% of patients requiring additional endoscopic procedures[43].

Stent anchoring: Malignant strictures, perforations, leaks, and fistulas are frequently treated with covered self-expanding esophageal stents, nonetheless, stent migration occurs frequently in up to 40% of cases. Clips and snares have been used for stent fixation; however, they present some technical challenges. Recently endoscopic suturing has become the preferred method for securing stents placement. Of 125 patients with benign UGI diseases, such as strictures, leaks, fistulas and perforations who underwent stent placement were analyzed and showed a reduction in migration rates from 33% to 16% with suture fixation[44]. A meta-analysis reviewed 14 studies involving 212 patients and found a 17% migration rate after endoscopic suture fixation, patients had longer time till migration, and better clinical outcomes overall[45]. A comparative study in esophageal cancer patients found that stent migration rates were more than three times lower in the suture fixation group[46].

Endoscopic suturing for GERD management: The increasing prevalence of GERD has necessitated the focus on new treatment approaches. While medical therapy remains the standard initial treatment, patients who do not respond to it often require anti-reflux surgery. To address the growing demand for less invasive alternatives, several endoscopic procedures have been developed. Although limited data is available on the use of the OverStitch device in treating GERD, some studies suggest it can be useful in managing post-esophagectomy reflux, also known as gastric tube-esophageal reflux (GTER). One animal study demonstrated the feasibility of using the OverStitch device to create an anti-reflux valve in a post-esophagectomy pig model. The study showed improved reflux angles and stable pH levels after the procedure[47]. In a clinical case, this procedure was replicated in a 69-year-old esophageal cancer survivor with severe GTER, leading to significant improvement in pH control and the patient's quality of life[48].

Peroral endoscopic myotomy: Achalasia, a common esophageal motility disorder, is typically treated with pneumatic balloon dilation or surgical cardiomyotomy. In recent years, peroral endoscopic myotomy (POEM) has emerged as a safe, minimally invasive alternative. The POEM procedure consists of four main steps: Mucosotomy, submucosal tunneling, myotomy, and mucosotomy closure. Proper closure of the mucosotomy is essential to prevent leakage of luminal contents into the mediastinum. This can be achieved with either endoscopic clips or the OverStitch device. A case-control study comparing mucosotomy closure with endoclips vs endoscopic suturing during POEM procedures found that clipping resulted in shorter closure times and lower costs compared to suturing. However, suturing proved advantageous in cases where larger defects were present, as clips may have been insufficient due to their limited jaw span[49].

Bariatric procedures: Obesity affects nearly two billion people worldwide, making it a serious public health issue. In the United States, obesity is the second leading cause of preventable death and is associated with several life-threatening conditions, including heart disease, diabetes, and cancer[50]. Although bariatric surgery is an effective treatment, complications such as leaks, perforations, and fistulas occur in 3%-20% of cases, with a mortality rate of 0.1%-0.5%[51]. Endoscopic therapies, including endoscopic sleeve gastroplasty (ESG), offer a minimally invasive alternative for weight loss and are increasingly popular among patients who do not qualify for bariatric surgery. During the procedure the OverStitch system is used to place full-thickness stitches along the greater curvature of the stomach, from the pre-pyloric antrum to the gastroesophageal junction in order to create a constrictive, sleeve-like shape.

A large study of 1000 patients who underwent ESG and were followed for 18 months found that the average total weight loss was 13.7% at six months, 15% at 12 months, and 14.8% at 18 months. The overall complication rate was low, with 0.2% requiring blood transfusions and 0.5% undergoing repeat ESG procedures. Improvements in hypertension, diabetes, and dyslipidemia were also noted[52].

Esophageal stents

The first report of the use of esophageal endoprosthesis for treating malignant dysphagia dates back to 1845 when a tube made of ivory was used to treat the obstruction. Since then, stent materials and procedures have come a long way. Nowadays, esophageal stents are used to alleviate dysphagia and obstruction brought on by various benign and malignant conditions.

Conditions treated by esophageal stents can be divided into two groups. The first group includes patients with malignant or benign dysphagia, the second group includes patients with esophageal leakage.

In the dysphagia group, esophageal stents are used to regain esophageal patency in case of esophageal obstruction due to malignant or benign conditions, the implantation of temporary stents has become more common in recent years as a therapeutic intervention for benign esophageal strictures that are resistant to treatment. An esophageal stent may be considered after the failure of repeated endoscopic bougie dilation and other endoscopic therapies. For this group a fully covered self-expandable metal stent (SEMS) may be the preferred choice.

In the esophageal leakage group. The leakage can be a result of iatrogenic and spontaneous benign esophageal perforation, anastomotic leakage after esophageal reconstructive surgery, or fistula. A covered esophageal stent may be used for sealing off the leakage in carefully selected patients[53,54].

Types of esophageal stents: There are two main types of stents self-expanding plastic stents (SEPS) and SEMS. In addition to these two primary types of self-expanding stents, three other varieties exist, distinguished by the degree of silicone or polyurethane coating; fully, partially, and uncovered. Partially covered stents differ from fully covered stents primarily in that the partially covered stents have very little metal or plastic exposed at the proximal and distal ends, which allows higher imbedding into the esophageal wall and limits migration compared to fully covered stents. On the other hand, uncovered stents have their whole metal or plastic base structure visible, which may allow tumor ingrowth, they also do not cover an esophageal perforation or fistula opening. But they do have a lower chance of migration[54,55].

(1) SEMS: There are two types of SEMS, the conventional SEMS made from stainless steel, and the other type which is made from a nickel titanium alloy (Nitinol) with the latter being the most commonly used currently.

Stainless steel stents offer the benefits of strong support, adaptation to deformation, excellent plasticity, and good structural compliance. However, they tend to have poor histocompatibility, and may lead to obvious inflammation and fibrosis of esophageal tissue.

Nickel titanium alloy stents on the other hand have better histocompatibility, excellent elasticity, moderate strength, special softness, and are available in the three types of covered, partially covered, and uncovered. Some disadvantages of them are that uncovered, and partially covered SEMS have high risk of restenosis, and covered SEMS are prone to migration[53,55].

(2) SEMS with anti-reflux valve: After SEMS implantation, the incidence of gastroesophageal reflux and accompanying problems varies from 20% to 80% for patients with lower esophageal and cardiac malignancies. The necessity of a SEMS that would lessen acid reflux in addition to relieving dysphagia particularly in cases when the patient was supine gave rise to the development of anti-reflux stents with rotators, valves, or one-way valves. These devices are useful for stopping reflux and, to a limited extent, for stopping the growth of fibrous connective tissue from the stent's bottom edge. SEMS with anti-reflux valves are made from titanium metal alloy and have the advantage of relieving dysphagia while also preventing acid reflux, they however have some risk of obstruction and migration[53,55].

(3) Drug-eluting and radioactive SEMS: Drug-eluting and radioactive SEMS can be used to treat cancers locally in addition to treating dysphagia. Drug-eluting stents (DESs) are widely used in the vascular fields, in the esophagus their use is limited, and they have been slow to develop. Medications like rapamycin, fluorouracil, docetaxel, and paclitaxel can be loaded onto DESs giving the stents the advantage of anti-tumor growth and mucosal tissue hyperplasia-reducing effects while maintaining esophageal patency and relieving dysphagia. This combination of properties makes DESs a promising aspect in esophageal cancer treatment.

Radioactive stents are the treatment of choice for advanced esophageal cancer. Radioactive I¹²⁵ particles are loaded onto the stent delivering radiotherapy to the tumor and rapidly relieving the dysphagia. When compared to conventional external radiation therapy, radioactive SEMS can target esophageal cancers directly, prevent dose attenuation from distant irradiation, and raise the radiation dose in the target region, all of which improve efficacy.

Drug-eluting and radioactive stents have the advantage of anti-tumor growth effect, lessen hyperplasia of mucosal tissue, quickly alleviate dysphagia, and directly affect esophageal tumors, however they may result in collateral damage to healthy tissues and the esophagus, as well as an increased chance of stent migration following recovery[53,55].

(4) SEPS: Originally, the SEMS that were on the market were either completely uncovered or just partially covered, the exposed metal wires in the SEMS could easily damage the tissues and the friction and contact between the tissue and the exposed metal wire would quickly result in granulation tissue hyperplasia, which would cause restenosis and make extraction more challenging. These drawbacks show that the best course of treatment for benign stenosis is not SEMS. Thus, scientists started focusing on SEPS. SEPS are the only FDA-approved self-expanding stent for benign esophageal strictures.

SEPS were made of polyester plastic mesh and covered with a silicone membrane. SEPS have better histocompatibility than SEMS, seldom generate granulation tissue reactions, result in less tissue inflammation, and have a significantly lower risk of restenosis problems at either end of the stent. SEPs have had good therapeutic outcomes in cases of benign and malignant esophageal stenoses, esophagotracheal fistulas, and postoperative anastomotic fistulas, this is due to the fact that they do not cause significant tissue damage. SEPs are inexpensive, have good histocompatibility, and cause less tissue inflammation and restenosis. Due to limitations of the material SEPs cannot be compressed so they require pre- expansion they also have the same migration rate as fully covered stents. One prominent side effect of SEPs is chest pain due to excessive radial dilation[53,55].

(5) Biodegradable self-expanding stents: Biodegradable stents were created to overcome the complications of plastic and metal stents used in benign esophageal stenosis. They are made of synthetic degradable polymer [Poly (L-lactic acid) Polydioxanone]. The stents are broken down and absorbed by the body after a pre-determined period after they have concluded their therapeutic function thus eliminating the need for removing the stents. Good histocompatibility, non-toxicity, degradability, and the need for removing the stents have mad biodegradable stents a potential substitute for SEMS and SEPS, on the other hand some draw backs have been identified such as unexpected biodegradation which may lead to stent collapse and mechanical strength reduction[53,55].

And (6) VACStents GI^TM: VACStents were created to address the clinical challenge of maintaining luminal patency while applying endoscopic vacuum therapy (EVT) to perforations and surgical leaks in the GI tract (esophagus, stomach, intestine, colon). Endoscopic procedures treating surgical leaks and perforations of the GI tract have greatly reduced the morbidity and mortality of these conditions, however, those procedures are not without some drawbacks. The two most often utilized methods are endoscopic vacuum therapy using a polyurethane sponge with no stent, and totally covered stents without vacuum. A stent can stop the leak however it will move or be dislodged in more than half of the cases due to peristaltic dynamics. Furthermore, a stent cannot remove secretions from a wound. Conversely, the endoluminal vacuum sponge used in EVT provides all the advantages of vacuum therapy, but it obstructs the GI tract's transit, thus VACStents were created to combine the benefits of vacuum drainage-assisted wound healing with the covered stent's advantages.

VACStent GI^TM is made up of a self-expanding, superelastic NiTi stent coated in silicone and topped with a cylindrical polyurethane sponge. It is attached to a vacuum source by a catheter. The sponge is continuously suctioned at a pressure between -80 and -120 mmHg. Applying the stent is simple even in challenging topographic areas of the GI tract, the suction holds it in place preventing dislocation and it permits the passage of intestinal contents, enteral nourishment, and endoscopic tools. Initial clinical applications have revealed that the VACStent indeed realizes these design-related aspects clinically[56,57].

Indications of esophageal stents: (1) Malignant indications: Esophageal cancer is the 6^th leading cause of cancer related death worldwide. The main symptoms of esophageal cancer include dysphagia, odynophagia, and weigh loss. Approximately 50% of cases are metastatic by the time of diagnosis, this is due to the fact that dysphagia becomes evident after 50% of esophageal lumen is compromised, thus dysphagia suggests advanced disease.

Malignant dysphagia can be due to partial or complete esophageal obstruction by the tumor. This obstruction severely affects the patient’s ability to maintain nutrition, along with the malignant disease progression also exhausting the patient’s reserves. This leads to severe malnutrition and weight loss. Regardless of the clinical stage, malnutrition has to be addressed first which leads to the decision of stent placement early on.

On endoscopy, if the scope cannot pass the tumor, stents should be applied early. The alternative would be some kind of feeding access, either enteral or transnasal, but the advantages and disadvantages of each must be considered. One disadvantage is delays brought on either by complications or healing, this may cause delays in starting systemic therapy. as opposed to esophageal stents, which offer an almost instantaneous fix that permits spontaneous enteral feeding[53,58].

European Society of Gastrointestinal Endoscopy (ESGE) Guideline on esophageal stenting for benign and malignant disease recommends placement of partially or fully covered SEMSs for palliation of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass. ESGE also recommends the placement of non-expandable and expandable plastic stents for the palliation of malignant esophageal strictures[53,58].

ESGE recommends brachytherapy as a valid alternative, alone or in addition to stenting, in esophageal cancer patients with malignant dysphagia and expected longer life expectancy. ESGE suggests that SEMS placement with concurrent single-dose brachytherapy is safe and effective for relief of dysphagia[53,58].

For malignant tracheoesophageal or bronchoesophageal fistulas, ESGE guideline recommends esophageal SEMS placement, when fistula occlusion is not achieved by esophageal or airway prosthesis placement alone ESGE recommends the application of double stenting (esophagus and airway).

However, ESGE does not recommend SEMS placement as a bridge to surgery or before preoperative chemoradiotherapy because it is associated with a high incidence of adverse events. Other options such as feeding tube placement are preferable, also ESGE does not recommend the concurrent use of radiotherapy if an esophageal stent is present[53,58].

And (2) Benign indications: Since the early 2000s, the use of self-expanding stents for benign esophageal disorders has steadily expanded. Due to the diverse etiology of benign esophageal obstructions, conservative and surgical treatment varies widely based on the unique presentation of each patient. When stent coverage and type are properly selected, positive long-term outcomes are observed in such circumstances.

Esophageal strictures: Regarding esophageal strictures, Iatrogenic, neuromuscular, hereditary, or inflammatory factors can all result in strictures, at times the etiology is even multifactorial. Clinically, strictures manifest as dysphagia when the luminal diameter narrows to 12 mm or less, this usually requires dilation. However, Stents are occasionally utilized as part of the therapeutic approach to preserve the esophageal lumen after dilatation in the hopes that the stent will reduce the likelihood of stricture recurrence while the esophagus heals and remodels following the dilation.

Currently, ESGE recommends against the use of SEMSs as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and their cost. However, interim use of a SEMS may be explored for refractory strictures that fail to maintain an internal lumen of 14 mm for 4 weeks after the last dilation or those are unable to attain 14 mm diameter following biweekly dilations over 5 weeks. ESGE guidelines prefer fully covered SEMSs over partially covered SEMSs for the treatment of refractory benign esophageal strictures because of their very low risk of embedment and ease of removability. They also do not recommend the use of biodegradable stents over SEMSs in the treatment of benign esophageal strictures[53,58].

ESGE does not recommend permanent stent placement for refractory benign esophageal stricture; stents should usually be removed at a maximum of 3 months following insertion[53,58].

Anastomotic leaks: One of the most alarming side effects following an esophagectomy is anastomotic leak, which is said to happen 7%-12% of the time and may be a factor in up to 40% of post-operative deaths. Now that covered SEMS are being used, a stent can be inserted as soon as a leak is detected. This prevents mediastinum contamination right away and can make it possible to resume oral alimentation. The patient is then monitored clinically, and after 4-6 weeks, they return for stent removal and assessment of the anastomosis healing. Early reports showed treatment success rates for these leaks to be quite high, almost 100%. Since then, several analyses have shown that esophageal stents have an 80% clinical success rate when managing anastomotic leak[29,32].

ESGE recommends that temporary stent placement be considered for the treatment of leaks as early as possible. No specific type of stent is recommended, and the duration of stenting should be individualized. However, a review of a prospectively collected database showed that, in the case of anastomotic leak, removing the stent 2 weeks after placement reduced the risk of complications by 56% and did not compromise clinical success[53,58].

Perforation of the esophagus: Though they can happen anywhere throughout the esophagus, up to 80% of all perforations occur in the middle and distal esophagus. Up to one-third of patients are thought to have no underlying pathology, they may be a consequence of a benign stricture, or severe retching or vomiting (Boerhaave syndrome). In the other cases, it might be iatrogenic, resulting from trauma, foreign bodies, food impaction, or underlying cancer. Whatever the cause, esophageal perforation needs to be treated immediately, since it has a mortality rate of up to 25% even with therapy and much greater without it, mortality is usually due to sepsis[53,58]. Esophageal perforation can be treated with endoscopic clips or stents[59].

If perforation is detected, a covered SEMS can be immediately utilized to decrease the risk of mediastinal contamination. Even though covered SEMS have altered the therapeutic paradigm for esophageal perforations, it is still crucial to consult a thoracic surgeon as soon as possible. The patient needs to be admitted to the hospital, given the proper antibiotics and antifungals.

The use of covered SEMS has reduced the requirement for surgery to fix iatrogenic esophageal perforations, the stent is usually left in place for 4-6 weeks[53,58].

ESGE guidelines for stent placement in cases of perforations are the same as those of esophageal leaks and fistulas[53,58].

Esophageal fistula: Although they are uncommon, esophageal fistulas can develop in both benign and malignant conditions, they can also occur as a result of therapies including dilatation, radiation, or the implantation of a prior stent. Stents can be used as a bridge to surgery in cases of fistulas.

The first step is to determine the etiology of the fistula, some fistulas can be treated urgently with surgery without the need for stent placement. Some fistulas arise as a complication of stent erosion of the esophageal wall and perforation into the mediastinum, pericardium, or pleural space, in these cases the stent may have served as the nidus for the fistula and thus stent replacement is not a viable option.

Malignant fistulas can arise in patients with advanced esophageal cancer, these patients have T4 tumors and are most likely stage 4 with metastatic spread. These patients have an overall poor prognosis and are difficult to manage, however the placement of a palliative stent may allow for more time for work up and educating the patient about the limited available options[53,58].

Esophageal fistula can also occur in benign disease, fistulas between the esophagus and airways, lung, and pleural spaces have all been reported, they can be due to radiation, Chron’s disease, or infection. Stent placement in cases of benign fistulas prevents extra-esophageal tissue contamination and allows for oral alimentation, though oral alimentation should not be considered as the main route for caloric intake. Stent placement should be considered as a step in the treatment algorithm for fistulas, other steps such enteral feeding and treatment of the etiology should be taken. ESGE guidelines include stent placement in a multimodality treatment protocol for leaks, fistulas, and perforations to optimize the healing success rate and minimize the risk of adverse events[53,58].

COLONOSCOPY

Worldwide, colorectal cancer (CRC) is the second deadliest cancer and the third most common cancer in men and women. Approximately 1.14 million people in the United States alone have a history of CRC, and 1 in 20 may receive a colon or rectal cancer diagnosis at some point in their lives. By 2030, it is expected that there will be a 62% increase in this number[60].

With the exception of younger adults (those under 50), the incidence of new cases and mortality have been gradually dropping over the past few years, maybe as a result of improved treatment options and increased cancer screening[60].

The increase in the success rate in CRC diagnosis has been a result of several technological advancements. The most prominent technological advancement has been the introduction of flexible endoscopes and the ability to visualize and treat the GI tract directly. Hirschowitz presented the first flexible endoscope-which was entirely based on optical fibers-at the American Gastroscopy Society annual meeting in May 1957. Since then, Numerous innovative GI gadgets and diagnostic methods have emerged[60].

High-definition white light colonoscopy

With a resolution of 650000 pixels, current high-definition endoscopes enable extremely high resolution. Multiple studies have demonstrated an increase in the identification of adenomatous polyps with high-definition colonoscopy as opposed to conventional video endoscopy[60,61].

Increased visual field of mucosa

Growing colonic mucosa visibility by endoscope advancements could lead to a rise in adenoma detection rate (ADR). These advancements include: Cap-assisted colonoscopy: A transparent cap is fitted to the distal end of the colonoscope. Its job is to depress the colonic folds thus improving visualization of the proximal parts of the colon and increasing ADR[60,61].

EndoRings: Similar to Cap-assisted colonoscopy in that a silicon rubber device is fitted to the tip of the colonoscope to stretch the colonic folds during withdrawal. It allows for visualization of the proximal aspect of the colonic folds increasing the ADR. Endocuff is a similar device with the same function which also was found to increase the stability of the colonoscope during polypectomy[60,61].

Full-spectrum endoscopy colonoscope: Full-spectrum colonoscope is equipped with 3 cameras allowing for 330-degree angle of view, each camera allows for 140-degree angle of view up to 170-degree angle with a flexible tip. The images are displayed to the endoscopist on three side-by-side video monitors. Studies have shown a higher ADR with full-spectrum endoscopy colonoscope than forward-viewing standard colonoscope[60,61].

RetroView: Permits withdrawal in retroflexion. This maneuver is usually employed in the rectum but can be applied throughout the colon. It permits simultaneous viewing of the proximal and distal sides of inter-haustral folds which increases the ADR[60,61].

Third eye retroscope: Is a device that is inserted into the channel of the colonoscope, it allows for 180-degree retroflexion during withdrawal. Third Eye Retroscope complements the forward view and allows visualization of the proximal aspect of the folds increasing the ADR. Third Eye Panoramic was also developed, which does not need insertion into the instrument channel of the colonoscope. It is a single use video cap fitted with two side viewing lenses that is fitted onto the tip of the colonoscope[60,61].

The NaviAid G-EYE balloon colonoscope: Uses a reusable inflatable ballon that is fitted onto the tip of the colonoscope. Inflating the ballon on withdrawal causes flattening of the haustral folds and allows for better visualization in hidden areas[60,61].

Image-enhancing methods and in vivo microscopic evaluation of colonic epithelium

NBI: NBI utilizes filters that rotate in front of the light source to narrow the bandwidth of the light to blue and green wavelengths. It enhances blood vessels hence enhancing tumor detection which is usually more vascularized and appears almost brownish in color in contrast to normal mucosa which appears green. Studies comparing NBI to white light colonoscopy did not find a significant difference in ADR or detection of colorectal polyps, colorectal adenomas, or colorectal hyperplastic polyps, however compared to high-definition white light colonoscopy, NBI achieved higher rates of adenomas and polyp detection[60,61].

Chromoendoscopy: Uses color dyes to emphasize the architecture of the mucosal surface (typically methylene blue or indigo carmine) in order to detect cancer or colon polyps. Chromoendoscopy also makes it easier to identify and characterize flat and depressed colorectal neoplasms.

The SCENIC international consensus statement on the management of dysplasia in inflammatory bowel disease made a strong recommendation that, when compared to standard-definition white-light colonoscopy, chromoendoscopy increases the yield of dysplasia and is the recommended mode of surveillance[60,61].

Virtual chromoendoscopy (filter-aided colonoscopy): Makes use of novel light filters such NBI or software-based postprocessing methods for reflected light, such as NBI (Olympus Medical Systems Tokyo, Japan), FICE (Fujinon, Fujifilm Medical Co, Saitama, Japan), i-SCAN (PENTAX Endoscopy, Tokyo, Japan), and BLI (Fujifilm Co., Tokyo, Japan). It provides instantaneous modulation of the visible light spectrum and allows visualization of the mucosa under the filtered light. It can be readily utilized during most procedures and is much quicker and easier than chromoendoscopy[60,61].

i-SCAN, STORZ, and FICE professional image enhancement systems: Processor-integrated software applications that change the wavelength of the reflected light, several filters permit reconstructions of different wavelengths, enabling the selective and intensified visualization of tissue structure and surface. Studies have shown that i-SCAN and FICE have similar ability to differentiate adenomas from nonneoplastic polyps to chromoendoscopy.

ASGE has established that virtual chromoendoscopy has the capacity to reach the society's acceptable performance standards[60,61].

ME: Provides more detailed visualization allowing for polyp classification. ME aided pit pattern analysis of colorectal polyps is an objective and practical method of differentiation of neoplastic and non-neoplastic colorectal lesions[60,61].

Autofluorescence and endoscopic trimodal imaging: This imaging technique is based on the observation that some endogenous biological molecules become stimulated when tissue is exposed to short wavelength light, which causes the tissue to subsequently emit longer wavelength fluorescence light. Autofluorescence imaging can have false-positive based on the fact that autofluorescence is not specific for neoplasia. To increase the specificity of this technique it is often paired with high-definition endoscopy and NBI, this is called trimodal imaging and it enhances characterization of the detected lesions[60,61].

In vivo microscopic evaluation of colonic epithelium

CLE: This new method of endoscopic imaging enables real-time in vivo histology during endoscopy. It utilizes a low-power laser to illuminate tissue, enabling micron-level spatial resolution at 1000 × magnification permitting an “optic biopsy”, this can detect neoplastic lesions and CRC, help differentiate neoplastic from non- neoplastic lesions, determine the stages of adenomas, and differentiate adenomatous from non-adenomatous polyps. CLE covers a limited field of the mucosa, so it is commonly used to perform targeted biopsy[60-62].

Optical coherence tomography: Measure the optical reflectivity of tissue as a function of depth using infrared light. Improvements in the optical coherence tomography technology have made it possible to diagnose and distinguish between benign and malignant lesions in vivo and in real time[60-62].

Endocytoscopy: Is a new, extremely high magnification endoscopic method intended to offer superior in vivo evaluation of GI tract lesions. involves preparation of the mucosa, including intraprocedural staining allowing for microscopic visualization of the mucosa[60-62].

Spectroscopy: Classifies items depending on how they interact with light in real time. Dispersion of light can be either elastic or nonelastic. Raman spectroscopy is the most widely used nonelastic spectroscopy. It examines the vibrational and rotational characteristics of molecules and offers information about the molecular and metabolic makeup of the tissues. It permits early detection of precancerous and cancerous lesions, differentiation of normal and precancerous tissues, identification of flat lesions, and the detection of adenomatous and malignant tissues. A recent advance that is being studied is Magnetic resonance spectroscopy[60-62].

Autofluorescence spectroscopy and second harmonic generation: Uses the principles of autofluorescence and spectroscopy to detect the biochemical changes happening in dysplastic cells. Second harmonic generation technique measures the amount of extracellular matrix collagen protein and its alignment, thus differentiating malignant from nonmalignant colonic polyp tissue with high sensitivity and specificity. It can also objectively identify high-grade dysplasia and malignant lesions[60-62].

Colon capsule endoscopy

Since its advent in 2006, colon capsule endoscopy (CCE) has experienced numerous significant advancements. In 2009, the second generation of CCE was developed, with increased sensitivity and specificity of colorectal polyp detection due to increased view angle and an adjustable frame rate.

It has a high patient acceptance rate and is simple, painless, minimally invasive, and it can be self-administered, it does however require a more thorough colon prep. CCE has the disadvantage of the inability to do biopsies or forecast the histology of polyps[60,61].

AI in polyp detection and classification

AI has emerged as a transformative tool in CRC screening, particularly in the detection and classification of polyps. Early and accurate detection of polyps is critical to preventing CRC, and AI has demonstrated significant potential in enhancing this process.

In recent years, AI systems, especially those based on machine learning, DL, and CNNs, have been integrated into colonoscopy procedures to assist gastroenterologists in real-time polyp detection. These AI models are trained on large datasets of colonoscopy images and videos, allowing them to recognize subtle features of polyps that might be missed by the human eye. By continuously analyzing the visual data during the procedure, AI systems can flag potential polyps, improving detection rates, especially for small or flat lesions that are often more challenging to identify.

One of the most promising applications of AI in CRC screening is its ability to classify polyps accurately. By analyzing characteristics such as size, shape, and mucosal patterns, AI can differentiate between benign polyps (hyperplastic polyps) and those with a higher risk of developing into cancer (adenomatous polyps). This capability aids in decision-making during colonoscopy, as physicians can determine the appropriate course of action, such as biopsy, removal, or surveillance, based on AI-generated classifications. Research has shown that AI-assisted colonoscopy can improve the ADR, a key quality metric for colonoscopies, thereby reducing the risk of interval cancers. Moreover, AI has been shown to reduce inter-operator variability, ensuring a more consistent standard of care regardless of the physician’s experience level. The potential of AI to standardize and enhance CRC screening makes it a valuable addition to the field of digestive endoscopy, with the possibility of significantly impacting CRC outcomes.

As AI technology continues to evolve, ongoing studies are focused on refining algorithms, improving real-time performance, and expanding AI applications in endoscopic procedures. The integration of AI into CRC screening protocols represents a significant step forward in the fight against CRC, offering the potential for earlier detection, better treatment decisions, and ultimately, improved patient outcomes[63-67].

ROLE OF ENDOSCOPY IN TREATMENT OF COLORECTAL MALIGNANT, PRE-MALIGNANT, AND DYSPLASTIC LESIONS

EMR

Large colorectal polyps constitute the most common indication for EMR. The colon is the most common site for EMR. Over the past decade EMR has become a key technique of colorectal polyp removal. Surgical excision of the polyps was considered the standard procedure for treatment of large polyps; however, it was associated with a high rate of morbidity and mortality. EMR allows for an efficient and safe removal of polyps achieving high R0 (i.e., complete) resection rates[53,62].

Method: The method and techniques of EMR in the colon are the same as in EGD (discussed in detail in the EGD portion of the chapter).

However, there is one more technique of EMR that is more commonly employed in the colon than in EGD[53,62].

Underwater EMR: Underwater EMR is a novel approach that does away with the requirement for submucosal injection by using water to fill the lumen and propel the lesion toward the center and away from the underlying muscle layers (which will preserve their underlying circular form). Electrocautery is then used to resect the lesion. Theoretically, it has the advantage of preventing the injection procedure from causing cancerous cells to seed farther into the GI system. Furthermore, it may be helpful in circumstances that make a submucosal injection difficult, such as when the resection bed of the previous EMR has fibrosis[53,62].

Indications: EMR is considered a curative measure for resection of early cancer lesions limited to the superficial layer of the mucosa or the submucosa, and without invasion of lymphatic channels and vessels[27,68,69].

Well-differentiated or moderately differentiated tumors confined to the mucosa.

(1) Type 0-IIa lesions smaller than 2 cm; (2) Type 0-IIb lesions smaller than 1 cm; and (3) Type 0-IIc lesions smaller than 1 cm.

ESD

ESD allows for en bloc resection with very low recurrence rates, even for larger flat or sessile colorectal lesions, it also allows for accurate histopathological examination. It was developed to remove larger tumors than would be feasible with EMR[27,70,71].

Method: The method and techniques of ESD in the colon are the same as in EGD (discussed in detail in the EGD portion of the chapter)[53,62].

Indications: Japan Gastroenterological Endoscopy Society (JGES) 2015 guidelines: (1) En bloc resection is not feasible with EMR; (2) LST-NG, particularly LST-NG (PD); (3) Kudo VI-type pit pattern; (4) Shallow SM invasion; (5) Large depressed-type tumors; (6) Large protruded-type lesions; (7) Mucosal tumors with submucosal fibrosis; (8) Sporadic localized tumors in conditions of chronic inflammation such as ulcerative colitis; and (9) Local residual or recurrent early carcinomas after endoscopic resection[72].

ESGE 2015 recommendations: (1) Their recommendations were similar to those of JGES, recommended ESD for colorectal lesions with irregular or nongranular surface pattern and depressed morphology, especially if the lesions are greater than 20 mm³; and (2) With the exception of rectal lesions, the recommendation continued to recommend surgery as the gold standard treatment for lesions IIa + c, IIc, III, non-lifting lesions, or LST-NG > 20 mm[73].

American Gastroenterology Association (AGA) clinical practice update 2019: (1) Advised ESD for colonic lesions with the following characteristics: Rectosigmoid location; (2) Complex morphology (0-Is or 0-iia + Is); (3) Depressed component (Paris 0-iic); (4) Nongranular LST (adenomas) 20 mm in size; (5) Granular LST (adenomas) ≥ 30 mm in size; (6) Residual or recurring colorectal adenomas; and (7) Additional surgical intervention may be required for lesions that have undesirable features following excision[26].

Similar to the Japanese clinical guideline from 2015, the most recent Korean practice guideline from 2020 acknowledged that additional surgical intervention is necessary following endoscopic resection in cases of poor histopathological types (poorly differentiated adenocarcinoma, signet ring cell carcinoma, mucinous carcinoma, deep mucosal invasion, lymphovascular invasion, and intermediate-to-high grade tumor budding) because of the higher recurrence rate in lymph nodes[74].

Endoscopic full-thickness resection of colonic submucosal tumors originating from the muscularis propria

A cutting-edge technique that makes it possible to resect submucosal cancers, which are typically treated by colonic resection. With this novel approach, the tumor is removed while maintaining the integrity of the tumor capsule and with active perforation. Ultimately, the mucosal defect in the colonic wall will close with a nylon loop, enabling endoscopic closure[62].

Colonic stents

The primary purpose of enteral stent development has been to relieve the symptoms of incurable GI cancer. The conventional approach to treating malignant colorectal blockage, which calls for immediate medical attention, involved stoma creation and surgical diversion. However, the morbidity and mortality rates of this surgical modality were high, prompting the search for a new therapeutic modality for malignant GI obstruction. Enteral stents are now the first-line modality for palliative care, and many types are being developed for extended clinical usage beyond a merely palliative purpose[75].

Types: Though plastic stents are used in EGD, pancreatic, and biliary procedures. Colonic stents are mostly SEMS. They are usually made from stainless steel, or nickel-titanium alloy[75].

Indications: (1) Temporary colonic decompression in patients with acute malignant obstruction as a “bridge” to elective surgery; (2) Long-term colonic decompression in patients with obstruction due to an unresectable colonic carcinoma; (3) Long-term colonic decompression in patients with benign colonic strictures because of fibrosis associated with surgery or radiotherapy; (4) Temporary colonic decompression in patients with diverticulitis to permit elective surgical resection; and (5) Palliative treatment, for closure of ileocolic, colovesical, or colocutaneous fistulae[75].

CONCLUSION

The landscape of GI cancer diagnosis and management has undergone transformative changes with the advent of advanced endoscopic techniques. Innovations such as EUS, ESD, and CLE have significantly enhanced the precision of early cancer detection, staging, and therapeutic intervention. These technologies have enabled a shift towards minimally invasive procedures, offering patients improved outcomes, shorter recovery times, and reduced morbidity. The role of endoscopy is not limited to diagnosis; it has become an integral part of personalized cancer management. Through targeted biopsies, real-time visualization, and localized treatments, endoscopic interventions are bridging the gap between detection and therapeutic outcomes. The integration of AI into endoscopy has further enhanced this field, enabling real-time image analysis, improved polyp detection, and enhanced diagnostic accuracy. AI-driven algorithms are assisting clinicians in identifying subtle lesions that might be overlooked, thus increasing the sensitivity of cancer detection. As research continues to explore novel biomarkers and molecular targets, endoscopy is poised to play a critical role in the era of precision oncology, tailoring treatments to individual tumor biology. AI will also be key in personalizing treatment plans, predicting outcomes, and optimizing procedural efficiency, making the diagnostic and therapeutic process more precise and patient-centered. The manuscript currently provides a robust summary of the advancements in endoscopic technologies and their pivotal role in the diagnosis and management of GI cancers. However, future research should explore the integration of AI in endoscopic diagnostics. AI has already demonstrated potential in enhancing early cancer detection rates and reducing inter-observer variability. Developing AI models tailored to endoscopy datasets could further refine lesion identification and risk stratification. Additionally, optimizing existing endoscopic techniques for early detection of pre-malignant and malignant lesions remains a priority. Strategies to minimize procedure-associated risks, enhance patient comfort, and improve access to advanced technologies in resource-limited settings could significantly impact global cancer outcomes. The continued evolution of endoscopic technologies, coupled with AI-driven innovations, will likely expand the horizons of GI cancer care, enabling earlier detection, less invasive treatment options, and improved survival rates. While challenges such as access to advanced technology, the need for specialized training, and the ethical considerations of AI integration persist, the future of GI cancer management appears promising, with endoscopy at the forefront of these advancements. Ultimately, these innovations hold the potential to transform the lives of patients worldwide, making GI cancer a more manageable and treatable condition.