Effect of Time-Limited Training on Endoscopic Submucosal Dissection in an Ex Vivo Porcine Stomach Model: A Prospective Randomized Controlled Study

Abstract Introduction  Endoscopic submucosal dissection (ESD) is the first choice for superficial tumor resection. There is no report on whether the training effect is affected by limiting the operation time of each ESD operation. This study aimed to prospectively evaluate the efficiency of time-limited ESD training by using an ex vivo porcine stomach model. Methods  ESD was performed in accordance with the standard procedure on ex vivo porcine stomach model. The time-limited group required each operation time to be controlled within 30 minutes, and the nonlimited group did not limit the operation time. The en bloc resection rate, surface area of the resected specimen, procedure speed, and perforation rate were compared in the two groups. Results  Compared with the en bloc resection rate in the time-limited group, that in the nonlimited group was significantly higher in ESD-1 and ESD-2. In each ESD procedure, the median resection area in the nonlimited group was significantly larger than that in the time-limited group. The difference in median procedure speed between the two groups in ESD-1 to ESD-4 did not reach significance in the statistical analysis. The speed of ESD-5 in the time-limited group was significantly higher than that of the nonlimited group. The perforation rate of the time-limited group was similar to that of the nonlimited group. Conclusion  Limiting the training time does not help the trainees to complete large resection of lesions and reduce the perforation rate, but it may help to improve the operation speed.


Introduction
In recent years, the detection rate of gastrointestinal tumors, especially precancerous lesions and early cancer, has been increasing.This condition is mainly due to the great attention devoted to tumor diseases and the development of new digestive endoscopy technology.The improvement in detection rate has also promoted the development of endoscopic submucosal dissection (ESD), which has many advantages, such as absence of laparotomy, organ preservation, and rapid recovery. 1n the late 1990s, Japanese scholar Gotoda and others first reported the successful dissection of early cancerous lesions larger than 2 cm in diameter by using ESD.ESD is an effective and safe method for the treatment of early gastrointestinal cancer. 2,31][12] Therefore, endoscopists need systematic training before performing clinical ESD treatment procedures to reduce the incidence of complications, patient pain and costs.
Prior to ESD in the human body, we have trained on animal models, such as porcine stomach.][15][16][17][18] Researchers have not determined how long ESD operators should be trained in porcine stomach model training and how many operations should be completed before they can implement the operation in human body independently.The coronavirus disease 2019 (COVID-19) pandemic in the past 3 years has severely challenged on-the-spot centralized learning. 19The number of standardized ESD training institutions in many regions is still relatively limited.Full use of the limited training opportunities and time to achieve the training effect is important.Research on whether to limit ESD training time has not been performed.Therefore, this study aimed to investigate the differences between time-limited and nonlimited groups in the training of ESD in an ex vivo porcine stomach model to provide evidence for reasonable training methods.

Trainees
Twenty endoscopists with more than 10 years of experience in endoscopy and endoscopic mucosal resection, without ESD experience, were selected regardless of age and gender.Before using the ex vivo porcine stomach model for operation training, the trainees were introduced to ESD-related equipment and techniques online.The materials included the following contents (1) brief introduction of ESD equipment, such as endoscope and electric cutter; (2) basic steps of ESD in the stomach; (3) dual knife cutting techniques; (4) Insulated-tip diathermic knife (IT knife) cutting techniques; (5) common pitfalls to be avoided in ESD operation; and (6) complications in ESD and management.Then, the trainees reviewed videos of ESD procedures performed by experts with rich ESD operation experience.The trainees were randomly divided into two groups by using the random number table method with 10 participants each.The operation time for the time-limited group was 30 minutes, and the operation for the non-timelimited group ended with complete mucosal dissection.Each ex vivo porcine stomach model was used to train two trainees, and each group had five operation platforms.Each trainee underwent five procedures.

Ex Vivo Porcine Stomach Model
The porcine stomach of 6 to 9-month-old samples was used to make the training model, and a complete esophageal connection was required.On the night before the training, the frozen stomach was thawed at room temperature.The stomach sample was washed thoroughly with warm water before use, and food residue was removed from the stomach.The stomach was fixed in a 25 Â 15 Â 10 cm plastic box, and the open part of the stomach was tightly clamped with hemostatic forceps.The esophagus protruded through a hole at the top of the box and was fixed with a tube that could pass through the gastroscope.A metal plate connected with the electrotome was placed under the stomach as an electrode for the operation (►Fig.1).

Endoscopes and Attachments
The Olympus GIF-h190 upper endoscope (Olympus, Center Valley, Pennsylvania, United States) and ERBE VIO 300 D electric generator (ERBE, Tübingen, Germany) were used in all the training courses.The following settings were adopted for all operations: Endo-Cut effect 3 and 130 Watts.Coagulation settings were not needed because no bleeding occurred in the ex vivo porcine stomach.Dual knife (KD-650U; Olympus, Tokyo, Japan) was used for each phase of ESD.Olympus distal attachments (D-201-11804; Olympus, Tokyo, Japan) were utilized in all operations.All operations were performed with normal saline and methylene blue as the lifting solution.

ESD Operation Process
ESD was performed in accordance with the standard procedure.The dual knife was used to mark the circumference around the target area.Normal saline and methylene blue were injected to lift the lesion.The initial mucosal incision was performed at 12 and 6 o'clock by using the dual knife.The dual knife was also used to cut the mucosa around the mark.Submucosal dissection was performed after circumferential cutting of the mucosa.When necessary, additional injections were made to lift and expose the submucosa sufficiently to ensure complete dissection.ESD should be performed in the proximal-middle part of the stomach (►Fig. 2).Gastric antrum with thick mucosa should be avoided.The size of the resected area was determined by the trainees.Direct or inverted ESD operation was optional for the trainees.Clamping was required for perforation and obstruction, such as air leakage.

Outcome Parameters
The following variables were recorded: (1) time of ESD operation, which is the time from the first circumferential marking to the complete dissection of the marked gastric mucosa; (2) completeness of the ESD resection (en bloc, incomplete), which refers to whether all the premarkers around the mucosal lesions are included in the resected specimens; (3) perforation, which refers to whether an obvious defect occurs on the muscle wall of the porcine stomach during operation; and (4) resection area.The dissected specimen was removed from the stomach and nailed to a cork board, and the area was measured.When the specimen had an ellipse shape, the two largest diameters of the resected specimen were measured, and the area was calculated as area (mm 2 ) ¼ small diameter (mm) /2 Â large diameter (mm) / 2 Âπ.When the specimen was circular, the diameter of the resected specimen was measured, and the area was calculated as area (mm 2 ) ¼ π Â (diameter (mm)/2).Procedure speed was calculated in mm 2 per minute by using the formula procedure speed ¼ area (mm 2 )/time (minute).

Statistical Analysis
The data were expressed as mean AE standard deviation (SD).Chi-squared and paired t-tests were performed for statistical analyses.All statistical analyses were performed in Stata-Corp, College Station, Texas, United States.A p-value less than 0.05 was considered statistically significant.

Results
In the time-limited and nonlimited groups, 100 endoscopic procedures (50 time-limited and 50 nonlimited) were performed in the ex vivo porcine model.An overview of the data is presented in ►Tables 1 and 2.
The difference in median procedure speed between the nonlimited and time-limited groups in ESD-1 to ESD-4 did not reach significance in the statistical analysis (

Perforations
In ESD-1 and ESD-2, four perforations were observed in the time-limited group.In ESD-3 to ESD-5, one perforation occurred.In ESD-1 to ESD-5, three perforations, two perforations, two perforations, no perforations, and one perforation occurred in the nonlimited group, respectively.No

Discussion
The value of the ex vivo porcine stomach model in ESD training has been widely recognized. 20,21Given the wide  In addition, we recorded and analyzed the en bloc resection rate, resection area, procedure speed, and perforations of the two groups.From our records, we found that the en bloc resection rates of the first two operations in the time-limited group (5/10 and 6/10) were significantly lower than those in the nonlimited group (10/10).By the third operation, both groups could almost complete the operation.The resection area of the time-limited group was significantly smaller than that of the nonlimited group in each ESD procedure.We speculate that sufficient operation time can help trainees achieve successful en bloc resection and remove large lesions.After five operations, the procedure speed of all trainees increased.The speed in the fifth operation of the time-limited group was significantly higher than that of the non-limited group.Limiting the operation time could make the trainees pay attention to the training, and the resection speed was improved significantly.The perforation rate of the time-limited group was similar to that of the nonlimited group and gradually decreased with the increase in the number of operations.No significant correlation was observed between perforation and limited operation time, which can be reduced only by improving operation skills.Therefore, according to the data above, the benefits of improving the procedure speed cannot be viewed as the main basis for limiting the operation time in ESD training requirements.
After communicating with the trainees in the two groups, we found that the psychological pressure of the trainees in the time-limited group was higher than that of the trainees in the nonlimited group because of the time requirement.9][30] By limiting the time, this study increased the psychological pressure on the participants, resulting in some psychological quality training before the actual operation on the human body, which is also unexpected.
However, limiting operation time is also an additional pressure for actual clinical surgeries.In practical cases, the difficulty of ESD such as complex surgical sites, abundant blood vessels, large lesion areas, and fibrosis cannot be measured solely by the operating time to determine the success of the surgery.Therefore, limit operation time may be more beneficial for the psychological quality training of trainees during animal models training.In actual operations on human cases, senior doctors with ESD experience need to timely replace junior doctors who lack operation experience in performing actual procedures to ensure the success and safety of the operation. 31,32However, the specific replacement time is usually determined by experience.Although a limited time set cannot represent the specific situation of human surgery, if the primary operator fails to achieve effective dissection within 30 minute or if perforation is possible, then the need for replacement is not guaranteed.This information can be confirmed by further clinical study.
This study has several limitations.This study focused on a small sample of endoscopists.The ex vivo porcine stomach model was used, and this model does not involve the  treatment of intraoperative blood vessels and bleeding.Therefore, the conclusions still need to be confirmed using large samples and large-scale, live porcine stomach models.
In this study, endoscopists were trained in ex vivo porcine stomach models for the first time to limit the operation time.The results showed that limiting the training time did not help the trainees complete large resection lesions, but it was beneficial for improving the procedure speed.Perforation control, which requires endoscopists to have superb operation skills, was not related to operation time.However, this study also puts forward new opinions on limiting the operation time for the exploration of trainers' psychological quality training, and team cooperation in clinical practice.In short, limiting the operation time should be adopted depending on the actual situation of the training institution.

Fig. 1
Fig. 1 Ex vivo porcine model used for endoscopic submucosal dissection training.

Fig. 2
Fig. 2 Application of endoscopic submucosal dissection in the ex vivo model.(A) Confirmation of the mark.(B) Circumferential cut after submucosal injection.(C) Submucosal dissection of the lesion.(D) Postinterventional site of the resection.

Table 2
Date of the nonlimited group E S D -5 E nb l o cr e s e c t i oAbbreviation: ESD, endoscopic submucosal dissection.