Endoscopic polypectomy is the removal of colon polyps during colonoscopy. It is now performed as a routine procedure in most centers in Western countries.
The non-surgical approach to the treatment of precancerous colon lesions was proposed as early as the 1970s. In recent decades, endoscopic polypectomy has progressed due to improved colonoscopic techniques and ancillary facilities. Endoscopic specialists can perform relatively simple procedures such as removal of small polyps with a biopsy forceps or strangler, endoscopic mucosal resection (EMR) and endoscopic submucosal resection (EMD) for removal of large polyps or early colorectal cancer, reducing the need for surgical intervention.
The importance of polypectomy is to interfere with the natural history of colorectal cancer. Polyps are classified as micropolyps (≤5 mm), small polyps (6-9 mm), large polyps (≥10 mm), and giant polyps (>30 mm), and whether a polyp develops into a malignant tumor is directly related to size. Recent studies have found progressive adenomas detected by colonoscopy to be 5.6%, with the larger the polyp, the more likely it is to be a progressive adenoma, micro polyps 0.9%, sub cm polyps 1.7% and large polyps 73.5%.
However, some studies suggest that even small or micro polyps have a 9-10% chance of progressing to progressive malignancy, thus emphasizing population-based studies to examine and remove polyps, even if they are only small. The detection rate of polyps and adenomas (ADR) is considered to be the most important marker of colonoscopic quality because of the strong correlation between ADR and colorectal cancer risk, which has been clearly observed.
Colonoscopic polypectomy is a method to stop colorectal cancer, but it is less useful in the right side of the colon. Heterochronous cancer is colorectal cancer diagnosed within 5 years of negative colonoscopy, and its incidence rate is indirectly related to the quality of colonoscopy. Missed polyps are estimated to be the cause of most cases of ochronous carcinoma (50-80%), followed by incompletely resected precancerous lesions (15-30%) and finally new invasive tumors in genetically susceptible patients.
Serrated polyps need to be looked for carefully because they are important precursor changes for important heterochronic colorectal cancers. Endoscopists know little about these polyps and it is very challenging to see such polyps microscopically because their microscopic features are very unremarkable and margins are difficult to describe, leading to a high rate of missed diagnoses and incomplete resections. High-quality colonoscopy is therefore needed both to detect polyps or adenomas and to effectively remove them completely.
Many reasons are associated with low quality diagnostic colonoscopy and low ADR, such as the quality of bowel preparation and operator experience. Many efforts have been made to improve ADR, such as high-resolution white light endoscopy, pigmented endoscopy with added optical capabilities, retroreflective viewing devices, stained or virtual or electrochromic endoscopy, such as narrow-spectrum endoscopy with variable spectral imaging contrast enhancement, scanning and automated fluorescence confocal laser microscopy.
On the other hand, less attention has been paid to complete excision, and only recently some direct evidence on the completeness of polyp excision and the emergence of specific criteria for quality assessment of polyp excision have become available. The result of this lack of information is that there are many methods of polyp removal, especially for polyps smaller than 10 mm, but the variety of methods has led to dismal rates of polyp removal. Improving complete polypectomy includes improved techniques, development of virtual and technical training courses, and objective quality assessment criteria for polypectomy.
Despite its shortcomings, colonoscopic polypectomy has been very helpful in reducing the incidence of colon cancer and mortality over the past decades and is a cornerstone of future colorectal cancer prevention. In an article in Clinical and Experimental Gastroenterology, an Italian professor reviews the progress of polypectomy and its problems and complications.
Micropolyps and small polyps
General principles
Most polyps are micropolyps or small polyps encountered during routine colonoscopy, so the resection of these polyps has a significant impact on clinical outcomes. There is little data on which resection procedure is more appropriate for such polyps, leading different endoscopists to perform different polypectomies. In a survey of US endoscopists, 50% used biopsy forceps for 1-3 mm polyps, electrosurgical stranglers for 7-9 mm polyps, and no preferred method for 4-6 mm polyps.
Biopsy forceps polypectomy
Cold biopsy forceps polypectomy is quick, easy to perform and inexpensive. Unfortunately, this technique is significantly associated with incomplete polyp removal, increasing the risk of polyp recurrence and the development of heterochronic colorectal cancer. The reason for this may be related to bleeding after the first clamp, which obscures the view and makes the residual polyps difficult to detect and remove.
In Efthymiou’s landmark trial, EMR excised areas of polyps that were seen to be completely resected by biopsy forceps, and only 39% of micropolyps were actually completely resected. Histology was the only predictor of complete resection, and adenomatous polyps were more likely to be resected than hyperplastic polyps.
Follow-up studies have found that the rate of complete resection of adenomatous polyps with biopsy forceps is only 51-79%, so it appears that cold biopsy forceps are not the preferred method for removing small or micro polyps, except for those very small 1-2 mm polyps that can be completely removed in one pass. This technique can be used where polyp detection is difficult because the biopsy forceps are easy to manipulate.
Alternatives to traditional biopsy forceps include the use of larger cold biopsies, such as large biopsy forceps or polypectomy. In one study comparing large biopsy forceps with the traditional method of one-step forceps removal of polyps smaller than 6 mm, the rates of complete removal were actually quite different between the two methods, despite the visually higher rates of complete removal and shorter operative times.
Thermal biopsy forceps excision was once popular because it was thought to add electrocautery to the biopsy site, cauterizing the tissue surrounding the biopsy to increase the rate of complete polyp removal while inducing hemostasis. This method is no longer widely used because of the increased potential for complications and poor access to tissue specimens, and the rate of complete polyp removal is not superior to cold biopsy forceps.
Strangulation polypectomy
Cold strangler polypectomy is an easy-to-apply technique that is now widely used on small and micro polyps. Simply put, the endoscopist delivers the strangler to the appropriate location in the intestine, opens the strangler to encircle the polyp, slowly closes the strangler with the aim of grasping 1-2 mm of normal tissue around the polyp, and after complete closure of the strangler, the polyp is amputated. The polyp is sent for histological evaluation.
A recent comparative study found that cold strangler polypectomy was significantly superior to biopsy forceps resection, excluding the rate of complete histologic excision and operative time, and was particularly effective for polyps larger than 4 mm, with no significant difference shown for smaller polyps. The strangler resection is more expensive and has a lower recovery rate compared to biopsy forceps, but has not yet reached a statistical difference.
Some studies have compared cold and hot curettage for removal of small and micro polyps. When resection rates and recovery rates were not considered, no significant difference was shown between the two methods. Intraoperative bleeding was higher in the cold curettage group but resolved spontaneously without special intervention, and immediate or delayed bleeding was more common in the hot curettage group. Hot strangler polypectomy took longer and showed more postoperative abdominal symptoms.
All studies were concluded as follows: cold curettage is superior to hot curettage, and removal of small and micro polyps should be preferred. However, non-tipped polyps may benefit more from thermal strangulation.
Recovery of polyps
Most studies have not focused on the increased polyp recovery failure rate with strangulation. In a recent large retrospective study, small polyps, clot-free polyps, right colonic position, and cold strangulation all affected polyp recovery.
There is still debate as to whether micropolyp retrieval is necessary. The American Society for Gastrointestinal Endoscopy actually issued a statement in which two in vivo modes of operation are specified. One is called the resect-and-discard approach, where further pathologic evaluation is not necessary if the polyp is assessed as benign by the endoscopist in real time. The second approach, called the discard approach, is that micro-polyps located in the rectosigmoid colon that appear to be only hyperplastic endoscopically do not need to be removed or sent for examination, but simply left in situ.
These recommendations are based primarily on flow data because the likelihood of a micropolyp developing into a progressive adenoma is very low, micropolyps are common in the rectosigmoid region, and studies confirm that histologic evaluation of polyps in vivo is now very accurate. The cost analysis found that both the resection versus discard approach and the abandonment approach resulted in significant cost and time reductions and did not increase the risk of colorectal cancer, and it remains unclear whether these approaches can be used for serrated polyps.
However, it is important to note that the methods used in the statement are based on the assumption that polyps can be completely resected, an assumption that is unlikely to always hold true in reality, and some studies have reported a high incidence of progressive histologic changes in small and micro polyps.
Incomplete polyp resection is associated with only 1/3 of allogeneic cancers, and even though the rate of incomplete resection of small and micro polyps in ideal studies can still be 10-60%, the rate of incomplete resection in actual clinical practice should be much higher. Biopsy forceps resection has been repeatedly reported as an independent risk factor for incomplete polyp resection, increasing the risk of recurrence. Larger polyps, serrated adenomas, and endoscopist experience are all associated with incomplete resection. The above factors need to be considered in a comprehensive manner when performing polypectomy to reduce the possibility of incomplete resection and reduce heterochronic cancer.
In conclusion, cold strangler polypectomy appears to be the best procedure of choice for small and micro polyps, and further efforts are needed to increase the rate of complete polypectomy, not only by knowing the objective fact that incomplete polypectomy exists, but also by continuously improving resection techniques and facilities.
Large colonic polyps and lesions
General principles
Endoscopic treatment of large colorectal lesions is very complex. The current morphologic evaluation uses the Paris classification, which includes prominent lesions and polyp-like lesions (0-I), non-tipped lesions (0-Is) or pseudo-tipped lesions (0-Ip), or semi-pseudo-tipped lesions (0-Isp), depressed lesions (0-III), non-protruding, non-depressed, non-polyp-like lesions (0-II), or mildly prominent lesions (0-IIa) smooth lesions (0-IIb), the mildly hypoplastic lesions (0-IIc), or lesions with a combination of all three (0-Iia+IIc or (0-Iic+IIa).
Large 0-IIa lesions, also known as laterally transmitted tumors (LST), are further divided into granular LST and non-granular LST based on surface morphology. in vivo real-time microscopic staining features and vascular pattern characterization are key steps in the evaluation of colorectal cancer lesions. Ultrasound has recently been reported to be able to assess the depth of the lesion with a high degree of accuracy by means of an endoscopic microprobe ultrasound device, making ultrasound necessary in such cases.
Surgery has historically been the mainstay of treatment for large polyps; however, high complications, mortality, and cost have kept surgery from moving forward, and EMR and ESD are effective alternatives to surgery with lower complications and costs.
Careful evaluation of the gross and microscopic presentation of the lesion is critical to the choice of treatment type. For example, regardless of size, non-polypoid lesions are at greater risk for cancer than polypoid lesions, and non-granular LST lesions have a higher chance of submucosal invasion than granular LST. These factors influence not only the decision of whether to perform surgery or endoscopic resection, but also the choice of endoscopic treatment approach.
Microscopic evaluation, particularly narrow-spectrum image evaluation, can also provide information to help assess the in vivo histologic type (hyperproliferative, adenomatous, superficial, or deeply invasive) to determine if the lesion is suitable for endoscopic resection (lesion invades only the mucosa or the submucosa is less than 1 mm). Of course, if the lesion looks strongly suggestive of deeper invasion, such as a staining pattern of V or a depressed lesion, surgery should be considered.
EMR and EMD techniques
The EMR or EMD procedure also involves excision of the superficial submucosa or moderate submucosa, which makes it different from conventional polypectomy, which is performed only at the mucosal level.
EMR or EMD involves submucosal injection of saline, hypertonic fluid, or colloidal fluid followed by removal with a sclerotomizer. If the mucosa fails to augment, indirect signs of invasion should be considered and are not an indication for endoscopic resection. However, other factors may induce a similar response, such as previous excision or electrocautery to form fibrous tissue, India ink tattooing, and ulceration.
The inject-and-excise technique uses a dynamic submucosal injection of fluid to produce a protective layer and is most commonly used in the EMR technique. Simply put, the submucosa is separated and fluid is injected. If the lesion is less than 2 cm, it can be encircled with a rigid strangler. The strangler is lifted along the wall and slowly released slightly to release any mucosal muscle that may be pinched, and then excised.
If the lesion is larger, it needs to be excised in stages. The free edge of the lesion after the first resection is used as an anchor point for the next resection until the entire lesion is removed. All resected masses should be sent for histological evaluation.
There are various methods of ESD. Briefly, a submucosal injection is first performed proximal to the lesion, followed by a semicircular excision, followed by direct excision of the submucosa using various endoscopic knives, the contralateral half of the lesion is excised in the same way, and finally the entire lesion is excised. The other approach is slightly different, with a circumferential resection at the edge of the lesion, followed by a partial resection at the base of the lesion, and then either a complete resection with a strangler or a deeper circumferential resection until the entire lesion is removed.
Endoscopic mucosal resection
Swan has reported a 95% success rate for resection of non-tipped polyps larger than 2 cm by the fractionated EMR technique, with 90% of patients avoiding further surgery and significantly reducing comorbidities and complications as well as costs.
More recently, it has been reported that 90-96% of colon lesions larger than 2 cm can be effectively resected in single or multiple endoscopic fractions, allowing 85% of patients to avoid surgery and significantly reducing costs.EMR has also been successfully used to treat early colorectal cancer, especially when the cancer is confined to the mucosa, and for polyps that cannot be removed by standard strangulation polypectomy.
In conclusion, if EMR is performed by an endoscopist, it is successful in treating most colon lesions, with nearly half of the total resection rate, while the rest can be treated by fractionated resection, with only 3-10% of patients requiring surgical treatment.
However, the average recurrence rate of adenomas after fractionated resection of large or massive lesions following EMR is 25%. Predictors of recurrence after EMR have been reported to include lesions larger than 4 cm, the need for argon electrocoagulation, and the need for 6 or more fractional resections. The first endoscopic follow-up is usually 3-6 months after EMR, as most adenoma recurrences can be detected during this period. Late recurrent adenomas are those that appear after the first follow-up with negative endoscopic findings, which are less common and account for approximately 4% of cases.
A normal-looking scar with a negative biopsy indicates complete removal of the lesion. Methods to reduce recurrence after EMR include the use of argon electrocoagulation for residual wire weave at the resection margins or in the resection area, or hybrid EMR techniques such as circumferential pre-excision of lesions larger than 3 cm followed by whole block resection. In any case, adenomas are less likely to recur, are usually benign, and are easily treated endoscopically.
Factors associated with failed resection or incomplete resection include history of previous resection, proximal colon or ileocecal position, staged resection, 0-IIa+c morphologic changes, non-granular LST, staining pattern V, or submucosal carcinoma.
Factors associated with incomplete cure include inferior compression type lesions (0-III), as such lesions often have deeper submucosal infiltration. The addition of endoscopic mucosal ablation techniques to EMR is used for salvage treatment of previously incomplete fractionated resections for EMR or adenoma recurrence.
The most commonly used resection technique is EMR, while other types of EMR include cap-assisted EMR, fragment ligation EMR, or underwater EMR. cap-assisted EMR and fragment ligation EMR should only be used for rectal lesions because of the high risk of perforation in the colonic location.
Underwater EMR is a new fractionated resection technique that does not use a submucosal injection technique. Early trials have shown underwater EMR to be safe and effective, with low rates of delayed bleeding and no incidence of perforation. There was no early adenomatous tissue recurrence (1 year). This technique is easy to master and appears to be an alternative to conventional EMR and EMD.
Fractional EMR resection relatively increases local recurrence and is pathologically evaluated as suboptimal if there are further morphologic changes of invagination. En bloc resection is the preferred method for adequate histologic evaluation, as both horizontal and deep margins can be evaluated, and if all results are negative, a definitive diagnosis of complete resection can be made. Other features of curative resection include submucosal invasion of less than 1 mm, absence of lymphovascular invasion, and absence of poorly differentiated components. Fractional resection produces multiple tissue blocks, making histologic evaluation very difficult.
Endoscopic submucosal resection
ESD is a new technique that is more difficult and time-consuming to perform, but is effective in overcoming the disadvantages of EMR. ESD is primarily used in Japan, but is slowly penetrating to the West. Because there are no standard indications for ESD, it is usually used to manage difficult lesions such as those larger than 2 cm, non-granular LST or V-stain, especially when high-grade heterogeneous hyperplasia, cancer, or superficial submucosal lesions are suspected, when other endoscopic techniques have failed or make whole lesion resection impossible, or to disseminate lesions in ulcerative colitis.
A recent systematic evaluation and meta-analysis showed that ESD is very effective in treating lesions larger than 2 cm and recurrence after EMR, with an R0 resection rate of 88% and zero recurrence after R0 ESD resection. Moreover, the R0 resection rate in Asia is higher than that in Europe, which may reflect cultural and technical differences.
EMR vs. ESD
Two studies compared EMR versus ESD for large colorectal lesions. The first study found higher block resection and cure rates and lower recurrence rates in ESD, but longer treatment time and a possible increased incidence of perforation. the low recurrence rate in the ESD group was associated with a higher block resection rate, as the recurrence rate was 13% in patients who did not receive a block resection, similar to that of fractionated resection EMR. the recurrence rate was increased in the EMR group with fractionated resection compared to block resection, but block resection and fractionated resection were equally effective in preserving The recurrence rate was increased in the fractionated resection group compared to the whole resection group, but was the same for whole resection and fractionated resection for preservation of the colon.
The second trial, a large multicenter prospective observational study, demonstrated a higher block resection rate in the ESD group, especially for lesions larger than 4 cm, and a preference for ESD for large lesions, especially flat or mixed morphology lesions.
Other conditions
EMR/EMD can safely remove the lesion even if it is located in a difficult area of the colon, such as close to the dentate line, the ileocecal valve or the entrance to the appendix, and should be considered when the lesion extends through the ileocecal valve into the ileum or appendix. Large stalked polyps can be removed by conventional thermolabile resector.
Endoscopic resection of large polyps in deep locations can be performed laparoscopically with full suturing of the resection site through a tissue deposition system, which is a new technique under investigation. Recently combined laparoscopic and endoscopic techniques have been used selectively for resection of large colonic lesions. Other heterogeneous and full-layer techniques are being tested in animal models. These developments are associated with rapid advances in treatment devices.
Complications
General principles
Although colonoscopy or colonoscopic polypectomy is generally safe, there are some risks associated with complications such as bleeding, perforation, and post-excisional syndrome. Most of these complications are self-limiting and are easily treated conservatively or endoscopically. Rarely, they are life-threatening or require surgery.
The incidence of complications from diagnostic colonoscopy is extremely low, and all complications are related to colonoscopic procedures, especially polypectomy. The majority of complications during polypectomy are related to electrocoagulation, which is included in all operative procedures for the removal of large polyps. The submucosal injection of fluid to create a protective layer is to prevent temperature paracutaneous injury, however electrocoagulation is not required for the removal of small polyps or micro polyps, with the exception of tipped polyps.
In fact, in the era of thermal biopsy forceps or thermal strangulation resection, injuries such as perforation and bleeding are common. Recent studies have concluded that cold biopsy forceps and cold strangulation polypectomy have fewer complications, so these two methods should be used as the standard for small polyps and micropolyps in terms of safety and quality of resection. Risk factors include multiple polypectomies, large lesions, right-sided colonic location, older age, and inexperienced endoscopists.
Nearly one-third of patients have mild gastrointestinal symptoms after colonoscopic polypectomy, including abdominal pain, bloating, diarrhea, and nausea, which usually resolve within 24-48 hours. Other rare but more risky complications include hematochezia due to splenic hemangioma tear, acute appendicitis, diverticulitis, hernia, intramucosal hematoma, bacteremia, and colonic rupture.
Hemorrhage
Hemorrhage can occur either immediately (at the time of polyp removal) or delayed (within 1 week or sometimes 3-4 weeks after surgery) and is the most common complication.
Small polyps and micropolyps
The immediate bleeding rate for small polyps and micropolyps is 0.5-2.2%, and delayed bleeding is less common at about 0.3-0.6%. Most bleeding is self-limiting and easily managed by endoscopy or hemostatic forceps or epinephrine. Some methods of bleeding prophylaxis, such as prophylactic hemostatic forceps or prophylactic argon electrocoagulation, have been proposed, but appear to be ineffective in preventing delayed bleeding in resection scars.
Most studies do not consider antiplatelet agents to have an effect, such as aspirin and NSAIDs, so international guidelines do not recommend routine discontinuation before colonoscopy or resection of small polyps or micropolyps. Clopidogrel appears to be associated with a high incidence of postoperative bleeding.
Anticoagulation has been reported to be a risk factor for bleeding on diagnostic and therapeutic colonoscopy, but recent studies have shown that continued anticoagulation does not increase bleeding after removal of small or micro polyps with cold strangulators, so discontinuation is not required, especially in patients at high risk for thrombosis. Polyp size is an independent predictor of bleeding, but the relationship between location and bleeding remains controversial.
Large lesions
EMR/ESD intraoperative bleeding and delayed bleeding rates are similar, 1-10%. Recent analyses have found an overall ESD bleeding rate of 2% that can be successfully treated endoscopically. Lesion size, right-sided colon, and aspirin use were risk factors for delayed bleeding. Staged resection and history of previous resection were not risk factors for delayed bleeding, and placement of a hemostatic clip after EMR appeared to have a protective effect.
The vascular supply to a tipped polyp is usually multiple and therefore increases the risk of bleeding. Epinephrine injection into the root of the polyp with the head, along with the ring-clamp technique, can successfully reduce the risk of bleeding after thermal strangulator polypectomy. Even epinephrine injection can only prevent immediate bleeding and has no effect on delayed bleeding.
Epinephrine injection is the most widely used method to prevent bleeding, and many authors prefer to use other techniques only in high-risk patients. Some predictors such as large tipped polyps, older age, type of current, histological type of polyp, diameter of the stem, and the use of anticoagulants or not increase the risk of bleeding.
Perforation
Either immediate or delayed perforation is the second most common complication of polypectomy. The risk of perforation is almost zero for small or micro polyps when cold polypectomy is used. Most perforations are actually related to electrocoagulation, so this technique is no longer used.
The risk of perforation is, as expected, higher with EMR or EMD for large lesions. EMR is the safer of the two methods, with a perforation rate of 0-1.5%. The most important factor for perforation in ESD is the lack of experience of the surgeon. Different authors have observed a decrease in all complications, especially perforation complications, with increasing experience and improved technical equipment.
Lesions larger than 5 cm or non-granular LST are the two main changes for perforation in ESD, and proximal colonic locations, especially ileum, are also factors for perforation because of the thin colonic wall in these locations, while rectal locations are less likely to be perforated because of the thicker wall and location in the retroperitoneum.
Recent risk stratification scoring systems have shown good predictive features such as whether the operation will be successful and the likelihood of complications after EMR resection of lesions larger than 2 cm. Future studies will be needed to further validate this scoring system. Most EMR or EMD perforations can be successfully treated by endoscopic placement of a hemostatic clip, with only a small percentage requiring surgery. The use of hemostatic clips and endoscopic sutures for the treatment of ESD-associated perforations also needs to be further evaluated.
Post-polypectomy electrocoagulation syndrome
Post-polypectomy electrocoagulation syndrome is a very rare complication, primarily presenting as an irritable abdominal cavity, caused by electrocoagulation, but with no evidence of perforation on CT. It occurs in 1.35-3.7% of large polypectomies and requires hospitalization in only 0.07% of cases. Characterized by fever, abdominal pain, and increased inflammatory markers (CRP and leukocytes), this presentation has a good prognosis and requires only conservative pharmacological treatment.