Ultra-minimally invasive endoscopic techniques and colorectal diseases: Current status and its future

Abstract

Colorectal diseases are increasing due to altered lifestyle, genetic, and environmental factors. Colonoscopy plays an important role in diagnosis. Advances in colonoscope (ultrathin scope, magnetic scope, capsule) and technological gadgets (Balloon assisted scope, third eye retroscope, NaviAid G-EYE, dye-based chromoendoscopy, virtual chromoendoscopy, narrow band imaging, i-SCAN, etc.) have made colonoscopy more comfortable and efficient. Now in-vivo microscopy can be performed using confocal laser endomicroscopy, optical coherence tomography, spectroscopy, etc. Besides developments in diagnostic colonoscopy, therapeutic colonoscopy has improved to manage lower gastrointestinal tract bleeding, obstruction, perforations, resection polyps, and early colorectal cancers. The introduction of combined endo-laparoscopic surgery and robotic endoscopic surgery has made these interventions feasible. The role of artificial intelligence in the diagnosis and management of colorectal diseases is also increasing day by day. Hence, this article is to review cutting-edge developments in endoscopic principles for the management of colorectal diseases.

Key Words: Colorectal disorders, Ultra-minimally invasive scopes, Advanced gadgets, Endoscopic intervention, Combined endo-laparoscopic surgery

Core Tip: Diagnostic and therapeutic endoscopy is evolving in the management of colorectal diseases. The rigid scopes have given way to flexible and capsule scopes. Conventional white light endoscopes have been replaced by high-definition and modified image enhancements. Now, both diagnosis and in-vivo histology assessment could be feasible. Therapeutic endoscopy has evolved to manage selective colorectal disorders for which surgery was considered the standard of care in the past. The role of robotics and artificial intelligence is indispensable.

INTRODUCTION

Diseases of the colorectum encompass various benign and malignant conditions with varied morbidity and mortality. Proximity to the anal opening makes the colon and rectum accessible to diagnostic and therapeutic colonoscopy. The first colonoscopy was developed from one made by Philipp Bozzini (1805), the father of endoscopy[1]. The initial colonoscopes were limited by less flexibility and poor illumination. Modern scopes facilitate cecal intubation, prevent loop formation, and patient satisfaction with fewer adverse events[2]. Thin-caliber colonoscopes, magnetic flexible colonoscopes, and capsule colonoscopes are getting popular due to lesser patient discomfort and better efficiency. The technical developments in colonoscopes include light sources, flexible and torque-stable shafts, fiber optics, four-way angulation control, charge-coupled devices for image sensing, and the ability to produce a high-quality digital image. Nevertheless, it is multifunctional as it can be used for suction, insufflation with air or water, and biopsy with a shaft. Presently, high-definition-white light endoscopy is the standard vision system[3] and the developments in this field are expanding (Table 1). Other advancements include endocuff vision, amplify EYE, and G-EYE devices to enhance the mucosa and improve the gaze of vision. The introduction of artificial intelligence (AI) algorithms has made endoscopists' jobs easier and more efficient for the detection of missing lesions which are prone to human errors.

Table 1 Technological advancement in endoscopic diagnosis and treatment of colorectal diseases.

No.	Techniques	Technology	Clinical use diagnostic/therapeutic	Ref.
1	Chromoendoscopy	Real-time tissue enhancement using biocompatible dyes	Polyp and adenoma detection, differentiation of benign from malignant lesions, dysplasia associated with IBD	[111-114]
2	Narrow band imaging	Physical spectral filters generate narrow bands of 415 and 540 nm in center wavelength	Adenoma detection, dysplasia associated with IBD	[115,116]
3	Blue light imaging	Narrowed spectrum LED light of 410 nm and 450 nm enabling haemoglobin excitation and a positive mucosal contrast	Differentiation of non-neoplastic from neoplastic lesions, in vivo histology	[117-119]
4	Autofluorescence endoscopy	Fluorescence of fluorophores differentiate tissues	Adenoma detection, differentiation of non-neoplastic lesions from neoplastic lesions	[120-123]
5	Flexible spectral imaging color enhancement	This differentiation is based on the surface capillary pattern	Differentiation of non-neoplastic from neoplastic lesions, in vivo histology	[124-126]
6	Linked color imaging	Pre-processing narrow band LED radiation and post-processing color technology to separate imported colors into red, green, and blue what enhances color differences	Polyp detection	[127-129]
7	i-SCAN	Enhancement of the image contrast through a real-time post-processing algorithm, basing the different reflective properties of normal and abnormal mucosa	Adenoma detection, in vivo histology, disease activity in IBD, detection of neoplasia in IBD	[130-133]
8	i-SCAN OE	Incorporation of a digital pre-processor optical enhancement to improve visualization of mucosal vascular pattern	Detection of pre-malignant lesions	[134]

IBD: Inflammatory bowel disease; LED: Light emitting diode.

Along with the diagnostic evolution of colonoscopes, the realm of therapeutic intervention is expanding. The first colonoscopic intervention was a polypectomy using loop snare-cautery[4]. Nowadays, therapeutic colonoscopy can be used for the management of lower gastrointestinal (GI) bleeders, colorectal strictures, malignant large bowel obstructions, colorectal perforations, foreign body removal, etc. The endoscopic resection of early colorectal cancer (CRC) becoming the standard of care as it is associated with fewer morbidity[5,6]. Hirschsprung’s disease where surgery was once considered the only treatment, nowadays per-rectal endoscopic myotomy has shown good results in a few case reports. Similarly for malignant colonic polyps, segmental colectomy was considered the standard of care, where endoscopic polypectomy is considered a reasonable treatment modality and recommended by NCCN guidelines[4]. Similarly, for post-colonoscopy perforation, surgical management was considered as the standard of treatment, with the advent of endoscopic skills, and gadgets like clips, it is possible to avoid surgery in these patients. In this article, we shall discuss the role of minimally invasive endoscopic techniques in the diagnosis and management of colorectal disorders and their prospects.

DEVELOPMENT OF ULTRA-MINIMALLY INVASIVE ENDOSCOPE

It’s a narrow caliber scope to reduce discomfort, require less sedation, and improve therapeutic efficacy. A randomized controlled trial (RCT) of 220 females in whom pain following colonoscopy was reported to be higher, has shown that ultra-thin colonoscopy was reportedly less painful than conventional colonoscopy[7]. It can be easily negotiated beyond the stenotic segment to assess the proximal bowel. In a prospective study on 100 stenotic CRC patients, Ito et al[8] found 65.5% synchronous lesions in the proximal colon. Magnetic flexible colonoscopy has a similar function as a conventional colonoscope; however, it is more patient-friendly due to less looping of the scope[9]. The mechanism includes a “front-pull” rather than a “push technique”. The forward mechanism prevents buckling of the instrument and resultant pain, and perforation. Capsule colonoscopy is a non-invasive method of screening; however, it requires aggressive bowel preparation as a small amount of debris can affect the capsule mobility. European Society of Gastrointestinal Endoscopy guideline recommends the use of second-generation capsules for screening of average risk of CRC where previous colonoscopy failed due to difficult scope progression[10].

DEVELOPMENT OF NEWER ENDOSCOPIC TOOLS AND GADGETS

Enhanced field of vision of colonoscope

The Third Eye Retroscope (TER; Avantis Medical Systems, Sunnyvale, CA, United States) is an optical technology to detect polyps located at the proximal folds and the flexures. In a pilot study of 29 human subjects, out of 38 polyps, 34 polyps could be detected with a forward scope whereas 4 additional polyps were detected using TER (11.8% increase in the yield)[11]. The newer version, Third Eye Panoramic (Avantis Medical Systems) uses a video cap containing two side viewing lenses fitted into the standard colonoscope limits the drawbacks of primitive TER i.e., technical learning curve, duration of the procedure, and cost[12].

The Fuse Full Spectrum Endoscopy^® colonoscopy (EndoChoice Inc., Alpharetta, GA, United States) has a high resolution and 330° field of view. In a multicentre RCT, Fuse colonoscopy reported a significantly lower adenoma miss rate (7.5% vs 40.8%, P < 0.0001)[13]. Hence, the use of Fuse colonoscopy for colorectal screening and surveillance can be more useful. The extra wide-angle view colonoscope could detect significantly more polyps compared to the standard one (68% vs 51%, P < 0.0001)[14], and the detection of polyps behind the folds was also significant (62% vs 47%, P = 0.0009)[14].

Technical advances to improve colonoscopic access

The NaviAid G-EYE System (SMART Medical Systems Ltd, Ra’anana, Israel) comprises the G-EYE balloon colonoscope and the NaviAid SPARK2C inflation system which facilitates the straightening of haustral folds and flexures. In a RCT, compared to standard colonoscopy, NaviAid G-EYE balloon colonoscopy could detect an additional 17 (81%) adenomas among 106 patients[15]. Cap-assisted colonoscopy is used to improve the visualization of colonic epithelium. A meta-analysis including 12 studies (6185 patients) reported the detection of significantly more number of polyps [odds ratio (OR) = 1.13; P = 0.030), lower polyp miss rate (12.2% vs 28.6%), and higher cecal intubation rate (OR = 1.36, P = 0.020) with cap-assisted colonoscopy compared to conventional colonoscopy[16]. EndoCuff and EndoRings are similar to the cap-assisted colonoscopy, the device mounted over the scope helps to flatten the colonic folds during the withdrawal, hence, improving visualization. An RCT of 500 individuals reported a higher adenoma detection rate (ADR) with Endocuff-assisted colonoscopy compared to standard scope (35.4% vs 20.7%, P < 0.0001)[17]. A meta-analysis (6038 patients) comparing the Endocuff vs conventional colonoscopy demonstrated an increase in ADR [risk ratio (RR) = 1.18], especially in those endoscopists with an ADR < 35%, thus, improving the efficiency of novice endoscopists[18]. The EndoRings works with similar principles and an RCT (CLEVER Study) has shown a lower adenoma miss rate (10.4% vs 48.3%, P < 0.001) and a lower polyp miss rate (9.1% vs 52.8%, P < 0.001)[19].

Image enhancing techniques

Conventional white light endoscopy has several limitations which were minimized by various techniques. Chromoendoscopy uses various stains during endoscopy to enhance differences in the mucosa, and dysplastic or neoplastic lesions that are not apparent in white light. A prospective trial of targeted use of dye in patients with inflammatory bowel disease (IBD), demonstrated a significantly higher detection of dysplastic lesions than in standard colonoscopy[20]. Currently, SCENIC guidelines for the management of dysplasia in patients with IBD strongly recommend the use of chromoendoscopy[21].

The limitations of dye-based chromoendoscopy (operator dependency, time-consuming, lack of standardization of dilution methods, need for additional instruments, risk of met-hemoglobinuria, cost-effectiveness, risk of carcinogenesis, etc.) can be abrogated with the use of digital chromo-endoscopy including narrow-band imaging (NBI), Fuji intelligent chromo-endoscopy, i-SCAN, blue laser imaging, linked color imaging, etc.[22-25]. American Society for Gastrointestinal Endoscopy strongly recommends the use of advanced imaging techniques by expert endoscopists[26].

In-vivo histology

Various technical advancements can be used to assess the type of epithelium during colonoscopy. Confocal laser endomicroscopy can help to differentiate benign from malignant lesions, advanced adenomas, and adenomatous polyps with high sensitivity and specificity without histology[27]. Endocytoscopy involves staining the colorectal mucosa and visualization at a higher magnification and its accuracy in differentiating benign from malignant lesions was 94.1% compared to 96% on histopathology for differentiating neoplastic lesions from non-neoplastic lesions[28]. Optical coherence tomography is based on the use of infrared light to measure the optical reflectivity of tissue and hence; the differentiation of benign from malignant lesions in real-time based on microstructural images with high resolution[29]. Spectroscopy is based on the principles of light scattering and the vibrational and rotational aspects of molecules provide clues about the type of tissue (benign vs malignant, adenomatous vs non-adenomatous)[30]. A study has reported an accuracy of 83% to 88% in spectroscopy in differentiating benign from malignant lesions[31].

Robotics in colonoscopy

Since the inception of robotics, its use in the medical field has been growing. The unique locomotion and adaptability of the colorectum make it feasible to use these new-generation colonoscopes[32]. The robotic colonoscope is more comfortable and less painful to the patient[33]. Currently, only the Endotics system (Era Endoscopy, Cascina, Pisa, Italy) is available for use and it is based on an electro-pneumatic self-advancing locomotion mechanism. This colonoscope is controlled by a hand-held device and consists of a disposable scope (called E-Worm) and it advances using two clampers located at both ends of the scope. Repetitive movements of lengthening and shortening allow the locomotion of the probe as that of a worm which is generated by a hydro-pneumatic system inside the probe. The advantages of the current Endotics system include reduced pressure on the colonic wall during advancement, reduced pain, discomfort, learning curve, complications, and comparable adenoma detection to conventional colonoscopes[34-36]. However, it requires a higher degree of colon cleansing due to the small suction channel[36]. Small series have reported fewer cecal intubation rates[34,35]. Other robotic systems that are not available for clinical practice are NeoGuide Endoscopy System, Invendoscope SC40, Aer-O-Scope System, ColonoSight System, Robotic-assisted Colonoscopy Capsule, etc. To curb the drawbacks of the Robotic Colonoscope, Li et al[37] developed a visual servo-based semi-autonomous manipulation of an electromagnetic actuated soft-tethered colonoscope which will improve the autonomy of conventional robotic colonoscope, to decrease the user workload, and promote its use in clinical practice.

AI in colonoscopy

Mr. John McCarthy coined the term “Artificial intelligence (AI)”, and since then it has evolved and infiltrated into day-to-day life and facilitated diagnostic and therapeutic interventions of medicine[38]. It helps to increase the ADR (CADe; computer-aided detection), and characterization of the lesion (CADx; computer-aided diagnosis). In a study by Abdelrahim et al[39] AI technique can detect more polyps compared to endoscopists (for < 5 mm polyps, AI can detect 81.2% polyps vs endoscopist 66%, P < 0.001, for > 5 mm polyps, AI can detect 87.5% polyps vs 42.3% with endoscopists, P < 0.001). The CADx can provide histopathological diagnosis using NBI, linked-color imaging, blue-color imaging, magnifying endoscopy, confocal laser endoscopy, autofluorescence imaging, etc. A recent systematic review and meta-analysis of RCTs (33 trials involving 27404 patients) of AI-aided colonoscopy vs conventional colonoscopy showed a significantly higher polyp detection rate [RR = 1.238; 95% confidence interval (CI): 1.158-1.323], ADR (RR = 1.242; 95%CI: 1.159-1.332), polyps and adenoma per colonoscopy[40]. The role of AI in the management of IBD is immense. In cases of ulcerative colitis, it helps to assess endoscopic remission. In a systematic review and meta-analysis of 18 studies (13687 patients), the pooled sensitivity and specificity of diagnosis of endoscopic remission were 87% and 92%, respectively and the area under the curve (AUC) was 0.96 (95%CI: 0.94-0.97)[41]. In Crohn’s disease, an AI algorithm based on computed tomography enterography can be used to assess the bowel and mesentery, which can predict the time interval to surgery with an AUC of 0.896[42]. Table 2 shows various commercially available CAD systems. Though AI-based colonoscopy algorithms have shown the potential to expedite diagnosis and further therapeutic intervention, however, there are a few limitations including ethical challenges, privacy, transparency and trust, cybersecurity, responsibility, bias, and data quality assurance[43,44]. These technical and technological advancements have made colonoscopy more comfortable and efficient (Figure 1).

Figure 1 Recent advances in colonoscopy.

Table 2 Commercial artificial intelligence algorithms and its clinical use in colorectal diseases[135].

No.	Product name	Company	Integration	CAD mode	Regulatory (country, year)	Clinical use
1	EndoBRAIN	Cybernet System Co. (Tokyo, Japan)	CF-290ECI, Olympus Co.	CADx	Japan, 2018	Colorectal polyps endocytoscopy-computer-aided diagnosis
2	EndoBRAIN-EYE	Cybernet System Co.	Olympus colonoscopes	CADe	Japan, 2020	Colorectal polyps endocytoscopy-computer-aided diagnosis
3	EndoBRAIN-PLUS	Cybernet System Co.	CF-290ECI, Olympus Co.	CADx	Japan, 2020	Image enhanced colonoscopy
4	EndoBRAIN-UC	Cybernet System Co.	CF-290ECI, Olympus Co.	CADx	Japan, 2020	Image enhanced colonoscopy
5	GI Genius	Medtronic Co. (Dublin, Ireland)	Multi vendors possible	CADe	United States, Europe, 2019	Colorectal polyps
6	DISCOVERY	Pentax Medical Co. (Tokyo, Japan)	Pentax colonoscope	CADe	Europe, 2020	Colorectal polyps
7	ENDO-AID	Olympus Co. (Tokyo, Japan)	Olympus colonoscopes	CADe	Europe, 2020	Colorectal polyps, real-time aid, texture and color enhancement imaging
8	CAD-EYE	Fujifilm (Tokyo, Japan)	Fukifilm colonoscope	CADe CADx	Europe, Japan, 2020	Colorectal polyps, real-time aid
9	EndoScreener	Shanghai Wision AI Co. (Shanghai, China)	Multi vendors	CADe	Europe, United States, 2021	Colorectal polyps
10	WISE VISION	NEC Co. (Tokyo, Japan)	Multi vendors	CADe	Japan, Europe, 2020	Colorectal polyps

ADVANCES IN MINIMALLY INVASIVE ENDOSCOPIC THERAPEUTICS

Colonoscopy has evolved from a diagnostic modality to interventions, for which surgery was once considered the standard of care. The first colonoscopic intervention was a polypectomy performed in the year 1969 using a loop snare-cautery device[45]. Colonoscopy has its place in interventions including localization of lower GI bleeding and management, dilatation of colorectal stenosis, management of colorectal perforation, foreign body removal, and many more[5,6].

Lower GI bleeding

The indications for surgery in lower GI bleeding are decreasing as 80% of lower GI bleeding resolves spontaneously and the majority of the rest can be managed endoscopically or through intervention radiology[46]. Most of the patients with lower GI bleed are at high risk for surgical intervention and the mortality rate for emergency surgery is nearly 10%[47]. Endoscopic treatment is commonly used are diverticular bleeding and angiodysplasias. The treatment options include clipping, band ligation, endoscopic detachable snare ligation, thermal cauterization, and epinephrine injection[48-50]. Epinephrine injection has a 20% rebleeding rate[51]. A clip can be applied to the neck of the diverticulum to stop bleeding[51]. Many studies have shown the superiority of band ligation for controlling diverticular bleeding and can be performed safely by trainees[52]. Similarly, in a meta-analysis of 384 colonic diverticular patients, band ligation was more efficacious than clips[50]. Colonic angiodysplasia accounts for 3%-15% of lower GI bleeding and it increases with age, argon plasma coagulation is the preferred treatment and reported efficacy in various studies[53].

Lower GI obstruction

Therapeutic colonoscopy can be used to manage lower GI obstruction. In cases of malignant colorectal obstruction metallic stent has shown its use[54]. In a meta-analysis of 12 studies, metallic stenting has shown a higher primary anastomosis rate, lower complications, and no difference in mortality when compared to emergency surgery[55]. Decompressive colonoscopy can be used for the management of pseudo-obstruction (Ogilvie syndrome)[56,57]. Colorectal stenosis is amenable to pneumatic dilatation. In a study of 40 patients with postoperative colorectal anastomotic site stricture, the restructure rate following pneumatic dilatation was 12.5% after a median follow-up of 5 years[58]. For ileocolic stricture in Crohn’s disease surgical resection is associated with more complications (32.2% vs 4.7%; P < 0.0001), however, there is less requirement for secondary surgery and longer surgery-free survival (11.1 ± 0.6 vs 5.4 ± 0.6 years; P < 0.001)[59]. Recently, endoscopic incision has shown potential use for anastomotic stricture dilatation[60].

Endoscopic access to sub-epithelial space is limited, however, recent developments in third-space endoscopy have expanded the use of endoscopic techniques in the diagnosis and management of mesenchymal tissues of the GI tract. Inoue et al[61] reported the first case of per-oral endoscopic myotomy for the treatment of achalasia cardia. Kulkarni et al[62] reported a case of per-rectal endoscopic myotomy in a 19-year-old girl for Hirschprung’s disease with clinical and manometry improvement at 9 months follow-up.

Colorectal malignancy

For endoscopically detected non-pedunculated colorectal polyps > 10 mm the conventional endoscopic mucosal resection (CEMR) is considered as an effective method with a technical success rate between 90% and 100%[63]. In conventional EMR, a cushion is created between the lesion and the muscle layer with a submucosal injection which decreases the risk of thermal injury and perforation, however, it increases the technical difficulties[63-66]. The risk of recurrence following CEMR is between 15%-50%[67]. To curtail the limitations of CEMR, Binmoeller et al[68] proposed an alternative way or EMR, underwater EMR (UEMR). Water emersion has certain advantages including reduction of haustral folds making easy snare capture[69]. Lenz et al[70] compared CEMR with UEMR in an RCT and UMER reduced the recurrence rate from 15% with CEMR to 2%.

Endoscopic submucosal dissection (ESD) is considered a better alternative to EMR with higher curative resection and lower recurrence rates[71-74]. However, it is performed using one endoscope which limits traction during the procedure leading to technical challenges. The recent development of traction wire (ProdiGI Traction Wire^®; Medtronic, Minneapolis, MN) can provide continuous traction throughout the procedure making it easier[75]. Another development is the use of double-scope ESD, where 2 separate endoscopes were used for separate traction and cutting, being used for upper GI and colorectal lesions[76,77]. Several modifications of traction during ESD include clip with line method, spring-and-loop with clip, clip and snare method, and magnetic method. Endoscopic full-thickness resection (EFTR) is indicated in adenomas, intramucosal carcinomas, and limited submucosal invasion (< 1000 μm below the muscularis mucosa) without any evidence of lymphovascular invasion. Other indications include technical difficulty in ESD and carcinoid tumors. Authors have reported that in the presence of fibrosis in the case of right-sided colonic lesions, recurrent lesions, or giant pedunculated polyps, EFTR remains a good treatment option[78-80]. The resection can be purely endoscopic or laparoscopic-assisted and closure of the defect can be performed using a clip, endo-loop, or a full-thickness resection device. However, these are technically challenging and yet to be used in humans.

Flexible endoluminal robotics helps to overcome the limitations of endoscopic resection by providing multidirectional traction using two robotic arms[81]. To meet the requirements various modified flexible endoluminal robots have been designed i.e., EndoMaster EASESystem (EndoMaster Pte Ltd, Singapore), Flex Robotic System (Medrobotics, Raynham, MA, United States), EndoLuminal Surgical System (ELS, ColubrisMX, Houston, TX, United States), flexible auxiliary single-arm transluminal endoscopic robot (FASTER system), etc. Preclinical studies on animal models have shown the utility of the EndoMaster EASE system in performing colonic ESD[82]. The Flex Robotic System was initially designed for trans-oral minimal access surgeries and it can be used for colorectal lesions extending up to 25 cm from the anal verge[83]. Fok et al[84] have reported a case series of rectal polyps at a mean distance of 8.3 cm from the anal verge, resected using Flex Robotic System. The ELS flexible robotic system uses wristed instruments and an endoscope and this platform is similar to the current robotic surgical system[85]. Compared to the EndoMaster EASE system, it can accommodate a 6-mm endoscope with 3 degrees of freedom, 2 instrument channels, 2 insufflation channels, and 1 working channel[85]. It can be used to perform endorectal surgery up to 55 cm from the anal verge. Pre-clinical studies on ex vivo resection in the porcine colon using an ELS flexible system have been performed[85]. The FASTER system uses a module attached to the distal tip of the endoscope which is a robotic arm with a grasper with 4 degrees of freedom[86]. It is mostly used for gastric lesions in pre-clinical studies and is yet to be applied to the colorectum[86].

Role in the management of post-surgical complications

Surgical re-exploration was considered the standard procedure for post-surgical complications even for small anastomotic leaks. However, with the use of various modalities i.e., clips, stents, and EndoSPONGEs, these morbid re-explorations could be avoided and a delay in adjuvant treatment could be minimized[87]. Anastomotic leak following restorative colorectal resection is the most feared complication as it can lead to morbidity and mortality with a reported incidence of 1%-19% among various studies[88-90]. Construction of a diverting stoma decreases morbidity following the leak, however, it doesn’t prevent a leak[91,92]. Radiological drainage is sometimes challenging due to the anatomical location of purulent fluid in the deep pelvis. The use of an Endo-SPONGE can be useful in these conditions which consists of a polyurethane sponge placed trans-anally into the leak cavity using a flexible sigmoidoscope. It drains the collection and helps to promote granulation tissue formation. The sponge can be cut into various sizes to allow it to fit into the cavity and it is changed every 48-72 h till the cavity heals[93]. However, the efficacy is better for acute leaks (75%) compared to chronic leaks (38%)[94]. Another method for closure of anastomotic dehiscence is the OverStitch™ suturing system described by Kantsevoy and Thuluvath[95] for the closure of post-polyethylene glycol tube removal long-standing gastrocutaneous fistula. Though it seems appealing, it is technically challenging in locations like the right colon due to poor angulation, margin maneuverability, and incompatibility with colonoscopy[96]. Endoscopic closure of small GI perforations has been known since 1997, however, the newly developed Over the scope clip^® system (OVESCO Endoscopy AG, Tuebingen, Germany) which consists of larger endo-clips can be used for colorectal anastomotic leaks. Radziunas et al[97] reported faster healing of post-LAR fistula using OESCO clips. Other methods of management of anastomotic leaks are the use of covered stents and fibrin glue. Though studies have reported positive outcomes with endoscopic techniques, however, it is important to realize that patient selection is paramount in treatment decision-making.

Colorectal anastomotic site stricture dilatation can be performed using a Hegar dilator or a balloon dilator. The use of endoscopic electro-incision can be performed by experienced endoscopists experienced in per-oral endoscopic myotomies. The endoscopic incision has shown 100% effectiveness at a follow-up of 33.75 months by Acar et al[98]. The reported incidence of perforation is also less in electroincision compared to bougie dilatation (0.1%-0.4% vs 4%)[99].

ROLE AS SURGICAL OPTIONS (ENDO-LAPAROSCOPIC SURGERY)

Trans-anal surgery

Trans-anal resection of rectal lesions has the risk of chronic pain after coccygectomy, rectal-cutaneous fistulae, wound infection, anal stenosis, and fecal incontinence[100,101]. Presently, there are trans-anal endoscopic microsurgery, trans-anal endoscopic operation, and transanal minimally invasive surgery and the basic difference among them is the platform and instruments used to perform local excision. These techniques are used for the excision of benign rectal polyps, and malignant lesions as a part of multimodality treatment of early rectal cancers, and in patients who are deemed unfit for radical surgery. A multicenter trial (The CARTS study) has assessed the role of long-course chemoradiotherapy followed by trans-anal endoscopic surgery after 6-8 wk for T1-3, N0 rectal cancers and reported a pathological complete response of 55%; however, local recurrence developed in 8.5%[102]. Similarly, The ACOSOG Z6041 study reported a 3-year survival rate of 88.2% for T2N0 rectal cancers for neoadjuvant treatment followed by transanal surgery[103]. Recently published GRECCAR 2 trial comparing total mesorectal excision and local excision in patients with < 4 cm T2-T3 rectal cancers with good response to treatment following neoadjuvant treatment showed no difference in local recurrence after long-term follow-up (local excision: 84% vs total mesorectal excision: 82%, P = 0.85)[104]. The upcoming STAR-TREC trial can answer the feasibility of wait and watch vs local excision vs total mesorectal excision for early rectal cancer (cT1-3b N0 tumors, ≤ 40 mm in diameter) following chemoradiotherapy[105]. The ASCRS recommends local excision for T1No rectal cancers and selective neoadjuvant treatment followed by local excision for T2 rectal cancers[106].

Combined endoscopic-laparoscopic surgery

Polypectomy of adenomatous polyps is considered for secondary prevention of CRCs. However, the resection of some polyps becomes technically challenging when they are flat or located behind colonic folds. Laparoscopy can help endoscopic polypectomy, known as combined endo-laparoscopic surgery (CELS). It starts with the creation of pneumoperitoneum and abdominal exploration. All necessary adhesiolysis is performed to aid colonoscopy. It can be performed in various ways as described below. The laparoscopic-assisted endoscopic resection (LAER) is laparoscopic manipulation of the colonic segment to facilitate intraluminal exposure of polyp and endoscopic removal. Another method is endoscopic assisted wedge resection (EAWR) where after endoscopic localization of the polyp, excision is performed with a laparoscopic linear stapling device. The endoscopic assisted transluminal resection (EATR) is used for lesions located near the mesentery. In this method, a small colotomy is performed after localization during colonoscopy. The lesion is elevated and divided using a linear stapling device. Closure of colotomy is performed with laparoscopic sutures or staplers. The endoscopic-assisted segmental resection is used for lesions not amenable to LAER, EAWR, or EATR. After colonoscopic localization, laparoscopic segmental resection is performed. Figure 2 shows different types of CELS. Studies comparing surgical resection with CELS reported quicker procedures and fewer complications[107-109]. No long-term studies are reporting the outcome of CELS for colonic malignancy, the upcoming LIMERIC-II trial will help to know the long-term oncological outcome of CELS for malignant lesions[110]. Table 3 shows studies reporting a comparison of CELS with surgical resection.

Figure 2 Types of combined endo-laparoscopic surgeries. A: Endoscopic-assisted segmental resection; B: Endoscopic assisted wedge resection; C: Endoscopic assisted transluminal resection; D: Laparoscopic-assisted endoscopic resection.

Table 3 Results of combined endo-laparoscopic surgery, segmental resection and outcome.

No.	Number of patients	Complications (%)	Length of stay (d)	Procedure time (min)	Cost (dollars)/others	Ref.
1	23 SR; 23 CELS	CELS: 13; SR: 47.8	CELS: 4; SR: 7	CELS: 135; SR: 200	-	Golda et al[107], 2022
2	11 CELS; 11 SR	CELS: 0; SR: 9	CELS: 0-3; SR: 2-5	CELS: 66.73; SR: 204.7	CELS: 5523.29; SR: 12626.33	Jayaram et al[108], 2019
3	5 CELS; 9 SR	CELS: 0; SR: 33.3	CELS: 1; SR: 5	CELS: 159; SR: 205	-	Lee et al[109], 2013

CELS: Combined endo-laparoscopic surgery; SR: Segmental resection.

As we have discussed, many acute, chronic, benign, and malignant conditions of colorectum can be managed endoscopically for which surgery was considered the standard of care, however, it was associated with morbidity. Studies comparing endoscopic vs surgical management in colorectal malignancies are shown in Table 4. Overall, the 5-year overall survival is better with surgical resection compared to endoscopic polypectomy, however, in high-risk patients, still endoscopic polypectomy is reasonable considering post-operative complications following surgery. In cases of malignant obstruction, both metallic stenting and emergency surgery had similar survival; however, surgery had more complications. Hence, patient selection is paramount for treatment decision-making.

Table 4 Results of published series on surgery vs endoscopic intervention in malignant colorectal polyps and colonic obstruction.

No.	Patients	Diagnosis	Complications (%)	Outcome (surgery vs endoscopy)	Ref.
1	Of 2077 patients: Surgical resection (1340), endoscopic polypectomy (737)	Malignant polyp	Surgery: 8.8. Endoscopy: 1.4	1-yr OS (92% vs 75%); 5-yr OS (88% vs 62%)	Cooper et al[136], 2012
2	Of 13157 patients: Surgical resection (11113), endoscopic polypectomy (2044)	Malignant polyp	-	Right colon polyps: < 20 mm polyp: 94.5% vs 94.3% (P = 0.9); 20-39 mm: 91.8% vs 74.2% (P < 0.01); > 40 mm: 92.4% vs 60% (P < 0.01)	Gangireddy et al[137], 2018
3	Of 31062 patients: Surgical resection (28469), endoscopic polypectomy (2593)	Malignant polyp	-	5-yr OS: 86.1% vs 80.6% (P < 0.05)	Lowe et al[138], 2020
4	Of 12 studies (meta-analysis)	Malignant obstruction	SEMS: 32.7. ES: 48.2 (RR = 0.61, 95%CI: 0.41-0.91)	Mortality (RR = 1.06, 95%CI: 0.55-2.04). Successful primary anastomosis (SEMS: 69.75% vs ES: 55.07%) (RR = 1.26, 95%CI: 1.01-1.57)	Cirocchi et al[55], 2021
5	Of 167 patients: SEMS (115), ES (52)	Malignant obstruction	SEMS: 20. ES: 30.8	5-yr OS: 85.6 vs 82.6% (P = 0.68)	Kim et al[54], 2023

CI: Confidence interval; ES: Emergency surgery; OS: Overall survival; RR: Risk ratio; SEMS: Self expanding metallic stent.

FUTURE DIRECTION

The twentieth century was credited with the research on the development and refinement of colonoscopes for better efficacy and fewer complications. Therapeutic endoscopy, as a subspeciality, subsequently came up in the later part of the century but with limited application in colorectal diseases. The incorporation of technology, tools, and techniques in the colonoscopes including AI has added another dimension to it. This newer version of scopes has resulted in quicker and more efficient diagnoses as compared to conventional colonoscopy with more accuracy, minimal discomfort, and wide therapeutic applications. Endo cytology is improving day by day, which can quicken the diagnosis of malignant pathology at an earlier stage. Robotic endoscopes, an upcoming tool may be used as a surgical robot to curtail the technical limitations of conventional scopes with broad indications and application in colorectal diseases. These innovations and newer versions of scope may avoid surgical intervention in select colorectal diseases in addition to its role in early and accurate diagnosis.

CONCLUSION

Minimally invasive techniques for the diagnosis and treatment of colorectal diseases are ongoing and allow earlier diagnosis and treatment with better outcomes. Ultra-minimally invasive colonoscopes present today are a result of thinner versions, flexibility, better vision systems, and mucosal enhancement tools. The use of AI has resulted in the minimization of human errors and improvement in the diagnostic yield. Development in smart glass has a further chance of improvement in diagnosis and intraprocedural professional guidance. Due to these newer innovations and newer versions of scope therapeutic colorectal intervention has increased. These minimally invasive colonoscopes loaded with gadgets and multiprong applications are being used both for benign (bleeding, obstruction, perforation) and malignant diseases (EMR, ESD, FTER). The use of robotic endoscopes with flexible instruments can be an emerging alternative to surgery in some selected diseases in the form of endorectal surgeries.