DOI: https://doi.org/10.21203/rs.3.rs-1464359/v1
Purpose: We sought to explore the application value of small-probe endoscopic ultrasonography (EUS) in combination with precut endoscopic mucosal resection (EMR) in the treatment of rectal carcinoids.
Methods: Biopsies were performed on patients with rectal submucosal swelling found by colonoscopy at our hospital, and patients whose pathological results were considered indicative of a neuroendocrine tumor were evaluated further. After EUS and computed tomography examinations, patients without peripheral disease or metastasis were treated with precut EMR.
Results: Thirty-eight patients were considered to have neuroendocrine tumors by pathological biopsy; of these, 37 patients were treated with precut EMR, and one patient with muscularis propria involvement was treated with surgery. The precut EMR operation time was 28 ± 12 minutes, the whole resection rate was 96.6%, and the complete resection rate was 100%. There were no cases of intraoperative perforation, all of which were located in the rectum. The lesion diameter range was 0.6 to 2.0 cm. There were 10 cases of immediate bleeding during the operation and one case of delayed bleeding after the operation. The length of postoperative follow-up was three to 12 months without recurrence or metastasis.
Conclusion: Small-probe ultrasound endoscopy can clarify the depth and diameter of rectal carcinoid invasion, demonstrating a high guiding value for the selection of treatment methods. Precut EMR is a safe, time-saving, and effective method for treating rectal neuroendocrine tumors less than 20 mm in diameter.
Rectal carcinoids can occur in several systems throughout the body, but the gastrointestinal tract is the most common location of such. There are certain differences in the distribution of carcinoids between European and American countries and Asian races. Studies in Asian populations have reported that rectal carcinoids are most common among the known gastrointestinal carcinoids [1, 2], while, in European and American studies, rectal carcinoids occupy third place among all gastrointestinal carcinoids [3]. In recent years, with the progress made ins and the development of endoscopy technology and the popularization of colonoscopy screening, the detection rate of rectal carcinoids has accelerated [4]. Carcinoids originate from chromaffin cells and neuroendocrine cells in the intestine and have unique biological and clinical features. Carcinoids generally do not secrete active substances or have carcinoid syndrome. Carcinoids can be insidious and not easily detected clinically, but they have the potential to develop into malignant tumors [5]. At present, there is no uniform method for the treatment of rectal carcinoids. In traditional cognition, surgery is the best treatment for carcinoids, and the surgical method is selected according to the size of the carcinoid, depth of invasion, and lymph node metastasis [6, 7]. At the same time, studies have shown that endoscopic treatment can have a better effect on carcinoids that measure less than 2 cm in diameter [8–10]. Small-probe endoscopic ultrasonography (EUS) is becoming increasingly widely used in endoscopy because of its simple operation and because it can provide references for the size, origin level, depth of invasion, surrounding lymph nodes, and blood vessels of the lesion, thus further guiding the resection of submucosal lesions [11, 12]. In this study, 35 cases of rectal carcinoid lesions were retrospectively analyzed to explore the value of EUS in combination with precut endoscopic mucosal resection (EMR) in the treatment of rectal carcinoids and to evaluate the safety and effectiveness of this approach.
A total of 38 patients who underwent colonoscopy and EUS diagnosis of carcinoids at the endoscopy center of our hospital from January 2019 to May 2020 were selected for study inclusion. Their lesions ranged in diameter from 0.6 to 2.0 cm. All patients were examined by colonoscopy and computed tomography (CT) before their operation. To be eligible for study inclusion, their tumor borders needed to be clear, without surrounding organs and tissues or distant metastasis. Patients who relapsed after previous surgical treatment and/or who could not tolerate anesthesia were excluded.
Prior to surgery, doctors talked with patients and their families in detail about the advantages and disadvantages of precut EMR as well as the possible risks of surgery. Study participants were those willing to undergo endoscopic treatment and follow-up and who signed the treatment consent form. This study complied with the appropriate ethical regulations.
In this study, the following equipment was used: a CF-H260 electronic colonoscope, hot biopsy forceps, and KD-612L IT nano-knife from Olympus (Tokyo, Japan); an AF-D2423PN disposable sterile endoscope injection tube from Shanghai Elton Medical Instrument Company (Shanghai, China); an SD-T-1823-25 disposable electric trap from Jiangsu Kangjin Medical Instrument Company (Jiangsu, China); an HA-L-4 disposable hemostatic clip from Jiangsu Anrei Medical Instrument Company; and a VI0200D+APC2 endoscopic electrosurgery workstation from Erbo Medical Equipment Company (Tuebingen,Germany). Also, the Angus UW-600 endoscopic water pump and Olympus CO2 pumping system were used (Tokyo, Japan). A submucosal injection of glycerin, fructose, sodium chloride, and methylene blue solution was adopted, and a transparent cap was installed on the colon lens.
Patients underwent complete preoperative examinations, except for those with contraindications to surgery and anesthesia. Oral anticoagulant and antiplatelet drugs needed to be discontinued for more than seven days. All patients were given polyethylene glycol 4000 powder (PEG-4000). Patients were instructed to prepare their bowels and adopt dietary restrictions, including a low-residue and low-fiber diet for 24 hours before treatment. Patients took 1 L of PEG-4000 orally at 9:00 pm on the day before the examination and another 2 L of PEG-4000 four to six hours before the examination until clean water was eliminated.
During testing, the operator cleaned the intestinal tract, located the lesions, injected normal saline into the intestinal tract, and immersed all the lesions in water. We inserted the small-probe endoscopic ultrasound device into the endoscope pipeline and performed EUS, recording results such as lesion size, shape, boundary, echogenic intensity and hierarchical origin, depth of infiltration, and the presence or absence of local lymph node metastasis.
A submucosal injection was completed to determine whether endoscopic surgery was appropriate according to the uplift signs of the lesions. The operation process (Figure 1) was as follows: First, (1) the submucosal injection was performed at the base of the lesion, and the lesion was fully lifted; then, (2) a KD-612L IT nano-knife was used to open the lateral edge of the lesion to avoid injury to the muscular layer. Next, (3) after the edge of the lesion was completely cut open, the lesion was encircled with a snare, and (4), after observing all the lesions, the snare was tightened and the diseased tissue was removed with electricity. Subsequently, (5) the wound was rinsed with normal saline to observe whether there was residual lesion and hemorrhage, and hot biopsy forceps were used to stop any bleeding and hemostatic clips were retained to close the wound to prevent delayed bleeding and perforation. Finally, (5) a pin was affixed along the edge of the lesion, the integrity of the incision edge was observed, the size of the lesion was measured and recorded, and the lesions were fixed with formalin solution and sent for pathological analysis.
Patients were asked to fast for 48 hours after surgery, with water given after 24 hours. Hemostatic drugs, circulatory fluids, and antibiotics were administered. We closely observed each patient's abdominal condition, vital signs, and stool color.
The surgical procedure; complete tumor resection rate; and postoperative complications such as perforation, bleeding, abdominal pain, and infection were evaluated. Colonoscopy was performed at three, six, and 12 months after surgery to observe the wound healing and ascertain the recurrence rate.
Among the 38 patients, 31 patients had lesions measuring 4 to 10 mm in diameter and seven patients had lesions measuring 11 to 20 mm in diameter. Under the endoscope, the carcinoids presented smooth submucosal eminences with a yellowish or grayish-white surface (Fig. 2). Most of the lesions were hemispherical and hard to the touch, with good mobility. Among them, one case with a lesion measuring 20 mm in diameter had surface erosion and roughness of the mucous membrane. Endoscopic ultrasonography showed that 37 cases were confined to the mucosal layer or submucosal layer, involving hypoechoic masses with clear boundaries and diameters of about 4 to 20 mm, without enlarged lymph nodes around the lesions. In one patient, the lesion had invaded the muscularis propria without lymph node enlargement around the lesion.
Abdominal CT showed no obvious distant metastasis. After communication with the patients and their families, precut EMR was performed in all cases, and the lesions were completely resected. A small amount of bleeding occurred in 10 cases during the operation. Heat biopsy clamps were placed to stop the bleeding, and hemostatic clamps were positioned to prevent delayed bleeding and perforation. One case with postoperative delayed bleeding was given endoscopic treatment and a hemostatic clip was used to stop the bleeding. There were no cases of perforation. After the operation, the patient fasted and was rehydrated, and prophylactic antibiotics were administered for three days; the patient reported no obvious abdominal pain or fever. One case of EUS showed invasion of the muscularis propria and was treated with surgery.
At three and six months, during postoperative re-examination, all wounds appeared to have healed well and showed scar-like changes. After that, colonoscopy was performed annually, and the study follow-up period was 24 to 36 months long. Among the 37 patients, eight patients were lost to follow-up, and the rest experienced no recurrence or metastasis.
The degree of malignancy of rectal carcinoids is related to their size. Studies have shown that rectal carcinoids measuring less than 2 cm in diameter rarely metastasize [7]. The consensus guidelines of the Neuroendocrine Society suggest that, when rectal carcinoids measure less than 1.9 cm in diameter, they largely are limited to the mucosal layer or submucosa, and, after excluding local lymph nodes and distant metastases, endoscopic treatment is feasible in these cases [13]. However, patients with lesions measuring greater than 2 cm in diameter or with concurrent muscle infiltration require surgical treatment [14].
Rectal carcinoids appear as pale yellow or grayish-white submucosal bulges under ordinary endoscopy. In most cases, their surface is smooth, although some may exhibit surface erosion or even ulcer formation (Fig. 2). Ordinary endoscopy cannot judge the depth of tumor invasion and the presence or absence of peripheral lymph node metastasis, so it cannot directly guide the treatment plan. Ultrasound endoscopy with a small probe can clearly observe the origins of the lesion as well as the level of the intestinal wall and can determine the size of the lesion and the presence or absence of infiltration of the muscle layer and surrounding lymph node metastasis. Therefore, it is necessary to conduct EUS before surgery to determine the depth of invasion and whether or not the surrounding lymph nodes have metastasized.
The main treatment methods for rectal carcinoids under endoscopy include EMR, endoscopic submucosal dissection (ESD), and transanal endoscopic microsurgery [15]. Studies have shown that, compared to the mEMR group, there is no significant difference in the complete resection rate or whole resection rate between the ESD group and the mEMR group [16–18].
In this study, a modified precut EMR approach was used. First, the surrounding mucosa was pre-incised around the lesion; then, the lesion was treated with snare resection. Compared with traditional EMR resection, pre-resection of the mucous membrane ensures the integrity of the resection. Studies have shown that ESD makes up for the deficiency of EMR, but the operation time is longer, the risk is higher, and the possibilities of bleeding and perforation are increased with the former. Compared to complex ESD resection, precut EMR can reduce the cost and time of lesion resection and the risk to the patient. Doctors who master traditional EMR resection can perform Precut EMR with a little learning.
In this study, when performing precut EMR, a small probe was used in advance to determine the size of the lesion, the depth of infiltration, and whether there was lymph node metastasis in the surrounding mucosa. A mixture of glycerol fructose and methylene blue was injected into the base to clarify the lesion and protect the muscularis propria. This technique can greatly reduce the risk of perforation and bleeding and increase the safety of lesion resection. After pre-incision of the surrounding mucosa, a snare resection was performed to ensure the integrity of the lesion resection.
This study has certain limitations; first, its results were affected by the operation level of clinicians and the proficiency of endoscopy. During the research process, various resection methods could not be compared with one another. Instead, bleeding, perforation, and complete resection rates of the various surgical methods were derived from references, and there may be a certain degree of bias as a result. In addition, the incidence of this disease is low, the sample size was small, and the analysis results may be biased.
In summary, precut EMR treatment is effective in treating carcinoids measuring less than 20 mm in diameter and no peripheral lymph nodes or distant metastasis. Combining this approach with small-probe ultrasound increases the safety of the treatment.
Disclosure of interest：
The authors declare that they have no competing interest.
Acknowledgments：
This work was supported by grants from Henan Provincial Government-Science and Technology Bureau (#LHGJ20191009);
Author Contributions Statement：
Siyu Zhang wrote the main manuscript text and Xiaoping Bian prepared figures 1-2. All authors reviewed the manuscript.
Table 1
Clinical data of patients with rectal carcinoids
|
Characteristics |
Number |
Immediate bleeding |
Delayed bleeding |
Perforation |
Postoperative pyrexia |
|
Age |
|
|
|
|
|
|
< 45 years |
17 |
4 |
0 |
0 |
0 |
|
≥ 45 years |
21 |
6 |
1 |
0 |
0 |
|
Sex |
|
|
|
|
|
|
Male |
21 |
5 |
1 |
0 |
0 |
|
Female |
17 |
5 |
0 |
0 |
0 |
|
Distance of tumor from the anal margin |
|
|
|
|
|
|
< 10 cm |
20 |
7 |
1 |
0 |
0 |
|
10–20 cm |
18 |
3 |
0 |
0 |
0 |
|
Lesion diameter |
|
|
|
|
|
|
4–10 mm |
31 |
2 |
0 |
0 |
0 |
|
11–20 mm |
8 |
8 |
1 |
0 |
0 |
|
Depth of invasion |
|
|
|
|
|
|
Limited to the mucosa and submucosa |
37 |
10 |
1 |
0 |
0 |
|
Invasion of the muscularis propria |
1 |
|
|
|
|