The rate of adverse events in the EMR group was 4. The median hospital stay in the EMR group was 7. In contrast, in the ESD group, the median procedure time was 90 The rate of adverse events in the ESD group was The median hospital stay in the ESD group was 11 d. In fact, only one patient with intraoperative perforation in the ESD group required emergency surgery immediately after ESD. Nevertheless, none of the patients in either group died due to adverse events.
Follow-up duration and 1-year follow-up rate were not significantly different between the two groups: Median follow-up duration, Three cases of local recurrence occurred in EMR, which were successfully managed by salvage endoscopic treatment.
No metastatic recurrence occurred in either groups. Twenty-eight patients in the EMR group were matched with 28 patients in the ESD group by using propensity score matching. The matching factors between both the groups, which are shown in Table 2 , were quite similar without any significant differences. All the absolute standardized differences ranged within 1. The median tumor size was 11 6. There were no significant differences in en bloc resection and curative resection rates between both groups en bloc resection rate: There was also no significant difference in the rate of adverse events between both groups 3.
Delayed bleeding in the EMR group was successfully managed using a conservative approach without surgery. None of the patients in either group died due to adverse events. As for recurrence events, only one local recurrence was observed in the EMR group, and no metastatic recurrence was seen during the follow-up period. Although ESD tended to result in a higher complete resection rate than did EMR, ESD was a significantly longer procedure and required longer hospital stay with a tendency of having a higher adverse event rate.
In fact, one patient in the ESD group required emergency surgery for a perforation. Local recurrent lesions in EMR were successfully treated by endoscopic resection. ESD for duodenal tumors achieved higher curability rates with a higher adverse event risk than EMR[ 11 - 13 ].
However, these previous studies, as well as the current study, were retrospective studies and not randomized-controlled trials. Therefore, there were some biases owing to the difference in the background characteristics of each group. For example, the tumor size was associated with the rate of adverse events after endoscopic resection and the en bloc resection rate[ 24 , 25 ].
In addition, the presence of a tumor in the distal part of the second portion, especially distal to the ampulla of Vater, was associated with the occurrence of delayed perforation after endoscopic resection[ 26 , 27 ]. Therefore, we performed propensity score matching in the current study instead of a randomized-controlled trial.
All such factors that were associated with the treatment outcomes were included as covariates; this contributed to the reduction of bias. Accordingly, the factors were quite similar between both groups after propensity score matching. Therefore, the current clinical study had fewer biases than previous studies.
Therefore, we believe that the results of the current study can be used to standardize the treatment method for SNADETs, especially for small lesions. These outcomes are similar to or better than those of previous studies[ 28 - 31 ].
In addition, although the curability of EMR in the current study seemed to be lower than that of ESD, the difference was not significant. The advancements in the endoscopic devices and the electrosurgical power unit, as well as advancements in the skill of the endoscopists, might have contributed to the better treatment outcomes.
During follow-up, three local recurrences before matching one local recurrence after matching were observed only in the EMR group, although no recurrence was observed in the ESD group. All recurrent lesions were attributed to the piecemeal resection but could be managed by salvage endoscopic treatment. Furthermore, no metastatic lesion was observed in either group during the follow-up period. The high rate of en bloc resection in the EMR group might contribute to the comparably low rate of local recurrence as that in ESD group.
Accordingly, the curative potential of EMR in the current study seems to be acceptable, even though the follow-up duration was short.
After matching, adverse events occurred in only 1 patient who underwent EMR, whereas adverse events were observed in 5 patients who underwent ESD, which were quite low compared with those obtained in previous studies[ 29 - 31 ].
Especially, no delayed bleeding occurred in ESD after matching. This result might be owing to the closure of the mucosal defect after ESD. In fact, in the current study, closure of the perforation site and prophylactic endoscopic closure of the mucosal defect were performed. In a previous study, prophylactic endoscopic closure contributed to the prevention of delayed bleeding[ 34 ]. Furthermore, complete closure of the mucosal defects after duodenal ESD reduced the risk of delayed adverse events[ 35 ].
The mucosal defect was closed in almost all patients who underwent ESD However, 1 patient who underwent ESD could not be managed conservatively, and, therefore, required emergency surgery. The time taken for the procedure and the hospital stay were significantly shorter in patients who underwent EMR than in those who underwent ESD. The results of the current study showed that a shorter procedure time for EMR than for ESD reduces the cost of medical staff, including the operator for the endoscopic procedure, assistant for manipulating the device, and assistant for monitoring patients.
In addition, the endo-knife used during ESD with hemostatic forceps is much more expensive than the snare used during EMR. Moreover, the low rate of adverse events might result in shorter hospitalization, thereby contributing to the cost of hospital stay.
A previous study also showed that patients who underwent ESD had lower medical costs than those who underwent surgery, although the data were of patients with early gastric cancer[ 36 ]. The current study had some limitations. First, this was a retrospective study and did not include a randomized population. There was a possibility of selection bias because lesions that could be easily snared were selected for EMR. Second, lesions treated with EMR tended to include adenomas, mucosal lesions, and small lesions.
These rates among two groups were similar after matching, but the comparison of treatment outcomes was limited primarily to such lesions. Therefore, it is questionable whether these findings could be generalized to adenocarcinomas, submucosal invasive lesions, or large lesions. Third, the sample size was relatively small owing to propensity score matching, even though this was a multi-center study.
A prospective study with a larger randomized population is expected to be conducted in the future. Fourth, the follow-up period in this study was insufficient to evaluate long-term outcomes. Median follow-up duration was Longer follow-up will be required to evaluate the accurate curative potential of endoscopic resection.
Such methods were not performed for treating SNADETs in the current study period or patients who underwent these procedures were excluded from this study. Accordingly, the treatment outcomes should be compared between conventional EMR and ESD and such new procedures in future studies. In conclusion, the results of our study demonstrated that EMR required a significantly shorter procedure time and hospital stay than did ESD, with comparable curative potential and a lower risk of adverse events.
Endoscopic treatments have been used as local treatments for superficial non-ampullary duodenal epithelial tumors SNADETs instead of surgery. Propensity score matching analysis was conducted to compensate for confounding differences between the two groups that may affect the outcomes. After matching, the treatment outcomes were compared between the two groups.
A total of patients were included and 28 pairs were matched. The rates of en bloc resection, complete resection, and adverse events were not significantly different between the two groups. EMR provides acceptable efficacy and safety with a significantly shorter procedure time and hospital stay than ESD.
This was a retrospective study with a relatively small sample size and follow-up duration. Therefore, further large-scale, randomized, prospective studies are needed. Advanced Search. This Article. Academic Rules and Norms of This Article. Supplementary Materials of This Article.
Supplementary Materials PDF. Citation of this article. Long-term recurrence rate at follow-up colonoscopy after 36 months. This will be observed from resected residual disease or, if not present, from biopsies of the post-polypectomy scar.
Complication rate within 30 days after treatment. Intraprocedural perforation is defined as the condition in which the abdominal cavity is visible from the colorectal lumen during the procedure because of mural tissue defects, that requires 1 prolonged admission or 2 surgery. Postprocedural bleeding is defined as bleeding within 30 days after the procedure resulting in 1 new presentation at the hospital, 2 hospital admission, or 3 repeated colonoscopy to obtain hemostasis.
Dose and type of sedation to be given is at the discretion of the endoscopist and will be registered. All colonoscopies will be performed with a high-resolution magnifying video-endoscope. A colloidal solution such as succinylated gelatine and dye will be used as the injection fluid, mixture with The purpose of this injection is to elevate the lesion away from the muscle layer, and to accentuate the plane of excision so that a wide and deep excision is achieved. Marking of the periphery of the polyp with coagulation is allowed to optimize the attempt of an en-bloc or R0-resection.
A snare is then passed through the channel and opened around the lesion. The snare is snugged around the lesion and pulled. Cautery is applied to resect the lesion. Only when en-bloc resection is not feasible, the endoscopist is allowed to perform the resection in a piecemeal fashion pEMR in as less pieces as possible. The number of pieces will be registered.
This will be applied in short bursts to coagulate the entire edge of the polypectomy site. Any remaining tissue in the polypectomy site will also be coagulated. In case of en-bloc EMR, adjunct therapy with coagulation will only be performed when remnant tissue is suspected and must be registered. A circumferential incision will be made using a ESD-knife. The incision must be placed on a distance of mm around the border of the polyp. This is because thermal damage otherwise makes it difficult to evaluate the histological resection margins after resection.
A complete or partial circumferential incision is performed first and then further dissection is performed after the lesion is adequately situated. This hESD technique consists of a circular incision around the lesion, with partial preparation in the submucosal layer that is sufficient to capture it with a snare in a single piece.
For both procedures length of the procedure will be measured, defined as the total time needed for resection of the polyp, measured from the minute the injection fluid is injected until the endoscopist finishes final inspection of the resection wound and all specimen pieces are collected and removed. For both procedures the opposite colonic wall of the resection site will be marked with India ink in case the adenoma is located in the sigmoid or descending colon, to ensure that the post-polypectomy scar can be found during follow-up.
For both procedures the following events are considered standard care, however, will be registered. In case intraprocedural perforation occurs, this will be treated using clips. In case of a minor bleeding from a small vessel, contact coagulation with the tip of a knife or coagulation with hemostatic forceps will be used for hemostasis.
In cases of a severe bleeding from a large vessel or artery, hemostatic forceps will be used for hemostasis. If a pulsating large vessel is exposed within the resection wound, clipping can optionally be used to prevent delayed bleeding.
If overnight admission is required, this will be registered including motivation. The resected specimen will be pinned on a paraffin, rubber or cork sheet so that the mucous membrane surrounding the lesion is evenly flattened and the mucous membrane surface can be observed, unless fragmentation as a result of piecemeal resection hampers this. In order to prevent autolysis after resection, the specimen must be fixed as quick as possible. To prevent drying, it will be soaked in a formalin solution.
Thereafter, the endoscopist is required to appropriately display the specimen so that the difference between the specimen and the clinical images is minimized and the tumor margin of the specimen can be judged.
The endoscopists will provide documentation an explanatory text to the pathologist so that the basic information on preoperative diagnosis, the site and morphology of the lesion, and the tumor size can be accurately conveyed.
After fixation, the specimen is photographed and inked. A tangent that touches the focus closest to the horizontal tumor margin is assumed. The first cut is carried out in the direction perpendicular to the tangent. The specimen is sectioned into slices at intervals of 2 mm parallel to the first cut. All slices are embedded in cassettes for histological diagnosis. Histological diagnosis of tumors is carried out in accordance with the Vienna classification of gastrointestinal neoplasia [ 26 ].
The histological type and resection tumor margins in mm horizontal and vertical of the lesion will be judged. A follow-up colonoscopy is performed 6 and 36 months after the procedure for all patients. The post-polypectomy scar is checked for residual disease. In case of macroscopic residual disease this is resected and send for pathology.
If not , three biopsies of the scar will be taken. If no recurrence is found at the 6-months colonoscopy, the next colonoscopy will be planned at 36 months. This is repeated until no recurrence is found with a maximum of three endoscopic resection attempts before referral to the surgeon.
The investigators will inform the subjects and the reviewing accredited medical ethics committee if anything occurs, on the basis of which it appears that the disadvantages of participation may be significantly greater than was foreseen beforehand.
The investigators will take care that all subjects are kept informed. Quality of data entry will be ensured through the electronical medical record, in which validation messages for users are created. In this way, a message will be shown to the data managers when something is incorrectly filled in for example: date in the past or future, unreliable low or high patient age.
An initiation monitor visit will be planned for all participating centers at the start of the inclusion period. On-site monitoring later in the trial will be done if necessary. In this way, high quality will be ensured throughout the study.
In addition, this study protocol has been peer reviewed by external reviewers from the Dutch Cancer Society KWF Kankerbestrijding , the funder of this trial.
The sample size is calculated for the primary outcome parameter recurrence rate at 6 months. Primary analyses will be conducted on the intention-to-treat principle. Categorical data will be presented with percentages. The outcome measures recurrence rate, R0-resection rate, surgical referral rate, and complication rate will be compared using a stratified analysis with a test for binary outcomes. For the perceived burden and quality of life analysis, data will be collected, presented and compared according to the user guides for the selected questionnaires [ 19 , 24 , 25 , 28 ].
QALY estimates for the first 6-month follow-up period i. An area under the curve AUC approach will be followed by interpolating between the observations provided by the patients. Effects will be discounted at 1. QALY estimates will be compared between both arms using non-parametric test when not normally distributed. Healthcare costs will be calculated by multiplying used healthcare services by the appropriated unit cost prices.
For all other healthcare services reference prices will be used, where available [ 30 , 31 ]. All costs will be expressed in euros. The actual healthcare costs occurring in both arms will be compared for the 6-month follow-up i. Costs estimates will be compared between both arms using a non-parametric test. In the economic evaluation, the balance between costs and effects will be assessed between both arms on both short i.
Results of both cost and effect measurement will be integrated and expressed as incremental cost-effectiveness ratios ICER showing additional costs per recurrence free patient and as ICER showing incremental costs per incremental QALY. Both sensitivity and scenario analyses will be conducted. Sensitivity analysis will be conducted for uncertain parameters, and scenario analysis will be used to model for example the impact of anticipated changes of reduced frequency or prolonged interval of follow-up colonoscopies after R0-resection.
This study will not only provide information on the effectiveness and safety of both treatment strategies, but will also give insights in perceived patient burden, quality of life, the costs and cost-effectiveness of both treatments. Given that all patients in this study will be followed for a total duration of 36 months, we will be able to evaluate both short-term i. We decided to include only patients with distal polyps in this trial. Not only because we expect that the risk profile for ESD will be more favorable in the rectum compared to the right colon, but also because most experience with ESD in the Netherlands currently exists with distal lesions [ 33 ].
We decided to include only non-malignant neoplasia in this trial, as we think it is unethical to randomize patients with suspected T1 CRC to the EMR arm. Given that EMR in polyps exceeding 20 mm in size is most often performed in a piecemeal fashion, inclusion of patients with suspected T1 CRCs in this trial would undoubtedly result in unnecessary referral of low risk T1 CRCs for surgery due to positive resection margins [ 34 ].
With regard to the outcome measures, we chose to evaluate the primary outcome measure recurrence rate after a duration of 6 months. Thus, 6 months seems the moment we are able to catch the vast majority of the recurrences. However, studies that looked at long-term recurrence rates also found that recurrence can occur up to 36 months after EMR [ 35 — 37 ].
Therefore, we feel a second outcome measure for long-term follow-up is obligatory for this trial. R0-resection was chosen as secondary outcome measure as this might be an important factor to decide for the frequency and interval of follow-up colonoscopies in future patients.
If our assumption is correct that a R0-resection does not show recurrence at long-term follow-up, this will offer an argument to prolong the interval and frequency of follow-up colonoscopies after ESD with R0-resection. Last, we decided only to apply a healthcare payer perspective when conducting the cost-effectiveness analysis. In Japan and Europe, there are guidelines that provide specific recommendations on the appropriate use of ESD. Although there are subtle differences between the 2 guidelines, generally speaking, ESD is endorsed for lesions that have a high likelihood of cancer invading the superficial submucosa and for lesions that cannot be removed by EMR due to fibrosis in the submucosal space or post-EMR recurrences.
EMR is relatively simple to perform, uses a limited number of devices, and has a long track record of being successful for the majority of dysplastic, precancerous lesions. As a result, some patients who are treated with EMR may require additional surgery, whereas if they had been treated with ESD, they may have been cured.
The main advantage of ESD is that it allows en bloc resection of any type of lesion regardless of size. Fortunately, the vast majority of perforations caused by ESD can be successfully treated by endoscopy without the need for surgery.
The rate of perforation is approximately 0. Delayed bleeding can occur, and the rate is roughly the same for both procedures. PD Studies have evaluated the cost-effectiveness of EMR and ESD compared with surgery, and those findings have shown a significant cost savings with the endoscopic approaches. PD Both procedures are advanced endoscopic techniques, and dedicated training is needed. Although EMR is frequently labeled as easier to perform, it is still a quite complex procedure.
Studies have shown that more than EMR procedures are required before the flatter portion of the learning curve is reached. The learning curve for ESD is even steeper, as the procedure requires dedicated time and effort. Training in ESD is particularly challenging in the United States, where mentorship may not necessarily be easily available. Therefore, in the United States, endoscopists who want to be trained in ESD follow an evolving pathway to competency. This pathway typically involves participation in hands-on workshops such as those organized by the American Society for Gastrointestinal Endoscopy, self-study on animal models, and observation of experts——which currently requires visits to a high-volume center in Southeast Asia.
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