Sessile serrated lesions involving the appendiceal orifice: Endoscopic diagnosis and treatment

Abstract

Some studies have reported that approximately 50% of appendiceal lesions are sessile serrated lesions (SSLs). Traditionally, surgical intervention has been the preferred method. Endoscopic procedures such as endoscopic mucosal resection (EMR) serve as alternative treatments for lesions at the appendiceal orifice (AO). However, EMR is not appropriate when the lesion margin within the AO cannot be visualized. When lesions extend into the lumen, extended laparoscopic appendectomy (ELA) or combined surgery can be used to resect the lesions. Compared with traditional surgery and EMR, ELA or combined surgery is a safer and more precise option that preserves the function of the ileocecal region. However, the need for coordination between surgeons and endoscopists, along with the requirement for staged procedures and multiple bowel preparations, increases the complexity of the treatment. In recent years, with the advancement of endoscopic full-thickness resection, endoscopic transcecal appendectomy (ETA) has been used to treat SSLs involving the AO. The use of choledochoscopy in conjunction with ETA can further enhance treatment precision. This integrated approach holds promise for replacing the combined endoscopic and laparoscopic surgical techniques. However, additional data are required to confirm its safety and efficacy.

Key Words: Sessile serrated lesions; Appendiceal orifice; Diagnosis; Endoscopic treatment; Endoscopic transcecal appendectomy; Choledochoscopy

Core Tip: The application of endoscopic full-thickness resection has enabled the feasibility of endoscopic appendectomy. When combined with choledochoscopy, it further enhances the accuracy of the procedure. This integrated approach offers a novel therapeutic strategy for sessile serrated lesions involving the appendix, potentially replacing the combination of endoscopy and laparoscopy. Future validation of its safety and reliability will depend on additional follow-up data.

INTRODUCTION

Sessile serrated lesions (SSLs) (previously known as sessile serrated polyps/sessile serrated adenomas) are precursor lesions that can evolve into colorectal cancer (CRC) via the serrated pathway[1], a specific type of adenoma commonly located on the right side of the colon.

Although appendiceal SSLs share microscopic morphology with that of the right colon, they display a distinct spectrum of genetic abnormalities[2,3]. SSLs frequently harbor V-Raf murine sarcoma viral oncogene homolog (BRAF) mutations in the right colon. By contrast, SSLs in the appendix are characterized by fewer BRAF mutations and a higher prevalence of Kristen Rat Sarcoma viral oncogene homolog alterations, which have also been implicated as key oncogenic events in low-grade appendiceal mucinous neoplasms[4-6]. Therefore, sessile serrated appendiceal lesions may be the precursors of appendiceal mucinous neoplasms.

Therapeutic methods for SSLs mainly include endoscopic therapies, such as cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic piecemeal mucosal resection (EPMR), and endoscopic submucosal dissection (ESD), and surgical therapies, such as partial colectomy. Because it is difficult to inspect the appendiceal orifice (AO), especially when these lesions are completely confined within the AO, routine colonoscopy is barely detectable. Endoscopic resection of SSLs involving the AO is particularly challenging. Surgical intervention has traditionally been the most prevalent method for treating SSLs of the appendix. Previously, we used cholangioscopic assistance to detect SSLs in the appendix and successfully performed an endoscopic appendectomy[7].

Herein, we present a review of SSLs involving the AO, focusing on endoscopic diagnosis and treatment.

ENDOSCOPIC FEATURES

SSLs are commonly located in the proximal colon (right colon and cecum)[8]. SSLs, which exhibit subtle mucosal characteristics similar to those of hyperplastic polyps, are frequently difficult to detect and diagnose with conventional endoscopy. However, these issues are often overlooked. The incidence and clinical features of SSLs have traditionally been poorly characterized owing to numerous classification changes and wide ranges in colonoscopy quality[1]. In 2019, the World Health Organization modified the classification of SSLs to incorporate a single crypt criterion, resulting in a decrease in inter-pathologist variability and an increase in the number of SSLs reported[9]. Research findings show that the proportion of serrated lesions reported as SSLs increased from 30.7% in 2019 to 38.3% in 2021[10]. Bone et al[11] found that in a New Zealand population, SSLs were diagnosed in 18.6% of all individuals undergoing endoscopic examination of the colon and in 29.0% of those who underwent polypectomy. SSLs were predominantly found in the right colon (65.1%) and were usually 0-9 mm in size (84.8%).

Most SSLs are flat-elevated lesions that are similar in color to their surroundings. Therefore, careful colonoscopy is necessary to detect SSLs. SSLs are subtle polyps with endoscopic findings similar to those of hyperplastic polyps; they are slightly elevated and pale. Nevertheless, they are typically > 5 mm in size and are frequently encased in a thin mucosal cap, in contrast to hyperplastic polyps. Mucus adhesion is an important feature in detecting SSLs[12-14]. The presence of endoscopic characteristics, including (semi) pedunculated morphology, double elevation, central depression, and reddish color, is useful for accurately diagnosing SSLs with dysplasia or carcinoma[15].

Narrow-band imaging (NBI) frequently reveals small dark dots within the apertures of SSL crypts. These dots are considered to indicate crypt dilations, a histological feature of SSLs[16]. The visibility of microvessels on the surface of a lesion can be enhanced by magnifying NBI. Expanded crypt openings, varicose microvascular vessels, and thick-branched vessels on the surface of SSLs are potentially unique endoscopic features of SSLs and have a high sensitivity for SSL diagnosis[17-19].

Magnifying chromoendoscopy is beneficial for the qualitative and quantitative diagnosis of SSLs with dysplasia or invasive carcinoma. The type II open-pit pattern, a hallmark of SSLs, is characterized by its high sensitivity and specificity[20].

THERAPEUTIC METHODS OF SSLS

Endoscopic resection of SSLs is associated with a higher rate of incomplete resection (30%) than adenomas (10%), which is primarily attributed to positive lateral margins. Consequently, endoscopists must establish stringent criteria for treatment methods. To facilitate comprehension, we categorize SSLs into two types: (1) Without dysplasia; and (2) With dysplasia.

Initially, when SSLs are devoid of dysplasia, lesions measuring less than 5 mm are deemed appropriate for monitoring because of their reduced likelihood of progressing to advanced malignancy[14]. CSP is an appropriate method for resecting lesions measuring < 10 mm. Piecemeal CSP is indicated for lesions exceeding 10 mm; however, it is associated with a relatively high recurrence rate[21-24]. Conversely, EMR demonstrates superior safety. Performing overall resection using EMR for lesions > 20 mm is technically challenging. In such cases, ESD and EPMR are considered viable options. However, the potential for local recurrence and residual malignancies, as well as the challenge of pathological assessment, are drawbacks of EPMR[25,26].

Nonetheless, when SSLs are associated with dysplasia, given the elevated recurrence rates of PCSP and EPMR, EMR is typically selected for lesions smaller than 20 mm, whereas ESD is preferred for lesions larger than 20 mm to ensure effective resection[27-29]. Invasive sessile serrated carcinoma or serrated polyposis syndrome necessitates surgical intervention to reduce the risk of CRC progression.

MANAGEMENT OF SSLS ASSOCIATED WITH THE AO

Certain studies have asserted that approximately 50% of appendiceal lesions are SSLs. Nonetheless, the unique anatomy of the appendix renders therapy contentious[30,31]. The significant limitations of endoscopic resection include the risk of appendicitis when performed deep within the AO and the inability to ensure a negative deep resection margin when the lesion infiltrates the appendix lumen. Surgical intervention remains the definitive standard of care; however, it is limited by the difficulty of ensuring a negative lateral margin without compromising the ileocecal valve, which often necessitates ileocecal resection.

In recent years, with advances in endoscopic techniques, several novel therapeutic approaches have been applied to SSLs involving the AO. These new methods hold promise for replacing traditional surgical treatments, aiming to achieve precise endoscopic resection of lesions and alleviate patient suffering.

Underwater EMR

EMR of polyps involving the AO is technically challenging and carries a high risk of perforation due to the thin wall and absence of the muscularis propria at the insertion of the appendix[32].

Binmoeller et al[33] introduced EMR as an innovative therapeutic approach for these lesions. After submersion in water, the AO substrate would autonomously flip. This enlarged the tube cavity, allowing for a more detailed observation of the AO. In addition, SSLs can be more effectively identified underwater, which is comparable to the principle of optical zoom.

They differentiated between patients with lesions observed only at the rim of the AO and those with lesions extending into the AO. The results showed that in the 3 patients who had rim-only lesions, underwater EMR (UEMR) was complete, with no residual lesions found during the follow-up examination. Among the 22 patients with lesions extending into the AO, 3 could not exclude the possibility of residual lesions extending to the appendix and were consequently referred for surgical intervention. This finding suggests that UEMR may be more appropriate when the lesion is limited to the rim of the AO.

Combined EMR and extended laparoscopic appendectomy

Given the limitations of EMR and traditional surgery, Huang et al[34] presented an algorithm to guide decision-making regarding the application of extended laparoscopic appendectomy (ELA), EMR, or a combined approach, based on tumor size and involvement of the lumen.

When the lesion involves the AO but does not extend into the lumen, standard EMR techniques are used for complete resection. When lesions extend into the lumen, two scenarios are considered. For lesions < 15 mm, ELA, which combines appendectomy with total cecal dissociation, is performed. For patients with lesions > 15 mm, EMR is initially performed to resect the lateral cecal part of the lesion, followed by ELA to treat the appendiceal edge.

The results showed that all patients involved, whether treated with endoscopy or surgery, achieved negative final margins. Among the patients treated solely with EMR, 2 (8%) experienced postoperative complications. One patient developed acute appendicitis, and another experienced post-polypectomy syndrome. Among the patients who underwent combined surgery, 1 (11%) had a perforation during the procedure. During follow-up, 1 patient (4.5%) in the sole EMR group had a 3-mm recurrent lesion at 14 months.

Compared with traditional surgery and EMR, the combination of EMR and ELA is a safer and more precise option that preserves the function of the ileocecal region. However, because ELA is an invasive procedure that requires coordination between surgeons and endoscopists, especially when the combined approach is required, surgery is generally performed in multiple stages, necessitating multiple bowel preparations, which is detrimental to patient compliance.

Endoscopic transcecal appendectomy

The advent of innovative endoscopic procedures, such as endoscopic full-thickness resection (EFTR), has introduced new possibilities for natural orifice transluminal endoscopic surgery and expanded endoscopic therapeutic alternatives for patients with gastrointestinal diseases.

Based on EFTR, Chen et al[35] proposed endoscopic transcecal appendectomy (ETA) as its extension, performing extracapsular dissection of the appendix for minimally invasive treatment of SSLs deep in the AO. The final closure was completed using an endoloop and clip placement. This was effectively performed in 4 patients with a favorable prognosis. Guo et al[36] demonstrated in a retrospective case study that all 13 patients with AO lesions were successfully treated with ETA without postoperative bleeding, perforation, or intra-abdominal abscesses. This study confirmed that ETA is a feasible, safe, and effective technique for treating AO lesions.

The primary procedural steps are as follows. After thorough cleansing of the lesion area, the lesion is first reassessed using white light, narrow-band interference technique, and indigo carmine dyeing. Subsequently, an ESD technique is used to create a submucosal incision, and the lesion along with the AO is subjected to full-thickness resection using the EFTR technique. After appendectomy, the appendix is retrieved from the intestinal lumen using a snare. Finally, the cecal defect is closed with an endo loop and metal clips using a two-channel endoscope. The specific operating procedure is illustrated in Figure 1[35].

Figure 1 Transcolonic endoscopic appendectomy for the sessile serrated lesion involving the appendiceal orifice[35]. A: Three-dimensional reconstruction images showing the appendix (yellow arrow) and adjacent bowels and vessels; B: Endoscopic white-light image showing the sessile serrated lesion (SSL) involving the appendiceal orifice (AO); C: Image from chromoendoscopy following indigo carmine dye spraying clearly showing the SSL; D: Intraprocedural view showing endoscopic full-thickness resection of the cecum tissue around the AO; E: Endoscopic dissection of the mesoappendix along the appendix by an insulated-tipped knife; F: Cecal defection; G: Intraprocedural endoscopic image showing clips and endoloop used for closing the cecal defect (yellow arrow: The dental-floss assistance); H: Cecal defect was perfectly closed by clips and endoloop after transcolonic endoscopic appendectomy; I: The specimen was calculated and examined; J: Endoscopic follow-up image showing the cecum 3 months after discharge (yellow arrow: The wound healing scar); K: Pathological confirmation and diagnosis of the SSL (bar: 100 µm): Increased gland diameter and enlarged opening; microbubble-like mucous cells; jagged crypts, widened and inverted crypt base. Citation: Chen T, Xu A, Lian J, Chu Y, Zhang H, Xu M. Transcolonic endoscopic appendectomy: A novel natural orifice transluminal endoscopic surgery (NOTES) technique for the sessile serrated lesions involving the appendiceal orifice. Gut 2021; 70: 1812-1814. Copyright ©The Author(s) 2021. Published by BMJ (Supplementary material).

Based on the aforementioned techniques, to better observe SSLs in the AO, our center previously proposed a method for diagnosing appendiceal SSLs in combination with a cholangioscope[7]. When SSLs involving the AO are found, further evaluation is conducted using a cholangioscope to facilitate better subsequent resection and make endoscopic appendectomy more accurate. As shown in Figure 2[7], the use of a disposable choledochoscope enables clear visualization of the internal margins of lesions within the appendiceal lumen, ultimately facilitating the completion of the endoscopic appendectomy.

Figure 2 Single-use cholangioscope-assisted diagnosis of sessile serrated lesions within the appendix[7]. A: Colonoscopy revealed a 20-mm laterally spreading tumor in the ileocecal region; B: A cholangioscope was utilized to further examine the appendix; C: The rough, granular mucosa was unveiled within the appendix cavity; D: Removed appendix. Citation: Yao J, Liu K, Zhao G, Wang Z, Wang X, Fu J. Endoscopic management of multiple sessile serrated lesions in both the ileocecal region and the appendix cavity. Endoscopy 2024; 56: E841-E842. Copyright ^©The Author(s) 2024. Published by Thieme (Supplementary material).

CONCLUSION

ETA offers several potential advantages over other therapeutic approaches. First, endoscopists can directly visualize the size of AO lesions, which aids in preserving the intestinal tract and maximizing the function of the ileocecal valve. Second, endoscopists can more easily access the AO lesion and appendix, facilitating accurate identification of the appendix and minimizing the risk of damaging adjacent tissues. Third, the ETA technique avoids surgical incision-related issues such as wound infection and incisional hernia, as well as preventing abdominal scarring. We compared these techniques, as shown in Table 1. Overall, ETA broadens the scope of endoscopic resection techniques and presents a promising alternative to combined endoscopic and laparoscopic surgery. Additionally, choledochoscopy can further assess the extent of intraluminal appendiceal lesions, enhancing the precision of subsequent resection and the efficacy of endoscopic appendectomy. Future validation of its safety and reliability will depend on additional follow-up data.

Table 1 Comparison of treatment methods for sessile serrated lesions involving the appendiceal orifice.

Therapeutic methods	Indications	Advantages	Limitations
EMR/underwater EMR	Lesions limited to the rim of the appendiceal orifice	Minimal invasiveness and ease of performance	Inability to visualize lesions extending into the lumen
ELA	Lesions extending into the lumen and < 15 mm	Preservation of ileocecal region function	Requirement for endoscopist-surgeon collaboration, staged surgery, and multiple bowel preparations
ELA + EMR	Lesions extending into the lumen and > 15 mm
Endoscopic transcecal appendectomy + choledochoscopy	Luminal extension of lesions	Maximized preservation of the ileocecal valve and intestinal tract; accurate identification of the appendix; reduced potential for damage to surrounding tissues; absence of abdominal scars; avoidance of surgical incision-related complications	Future validation of its safety and reliability dependent on additional follow-up data

ELA: Extended laparoscopic appendectomy; EMR: Endoscopic mucosal resection.