July 14, 2017
Endoscopic management of gastrointestinal tumors has progressed rapidly in the last two decades. Endoscopic mucosal resection (EMR), for example, was first developed to treat early gastric cancer but has since been widely adopted for other indications, including removal of sessile or flat neoplasms in the colon and early Barrett's adenocarcinoma. The relative simplicity, safety and efficacy of EMR have made it an accepted alternative to surgical interventions such as esophagectomy.
EMR's primary limitation is related to lesion size. Attempts to resect tumors larger than 2 centimeters (cm) often result in piecemeal resections, which are associated with higher local recurrence rates. Endoscopic submucosal dissection (ESD) was developed in Japan in the 1990s to overcome the limitations of EMR by facilitating en bloc resection of larger, superficial gastric tumors. The goal was to achieve curative resection and reduce local recurrence, according to Norio Fukami, M.D., whose specialty is the endoscopic management of gastrointestinal cancer at Mayo Clinic's campus in Arizona.
"EMR at the time could not completely remove gastric cancers of more than 1 to 2 cm, resulting in a positive or unclear margin. So there was a real need to expand the technique," he says.
Technique and advances
ESD proceeds in a series of steps, beginning with thermal marking of the lesion boundary followed by submucosal fluid lift. A circumferential incision is then made in the mucosa using a noninsulated tip knife or other dedicated ESD knife and a lifting agent is injected repeatedly into the submucosa to facilitate dissection of the tumor. This method results in en bloc resection of even very large tumors and allows assessment of deep and lateral margins — something not possible with piecemeal EMR.
In the last decade, a number of advances have made ESD safer and less challenging to perform. These include:
- The development of a wide variety of dedicated electrosurgical knives suitable for different procedural steps
- Chromoendoscopy or advanced imaging to better characterize the surface of a lesion and demarcate its borders
- Viscous solutions for submucosal injection, including some with autodissection properties
- Novel suturing devices and techniques to close defects or perforations as necessary
One of the most significant developments, according to Dr. Fukami, is electrosurgical units containing microprocessors that control the current waves, sense changes in electronic current in response to increasing tissue impedance and have the ability to modify the tissue effect accordingly.
"These devices provide a good clean cut that makes the procedure much easier," he says. "If you can cut without much bleeding, then there is less time, effort and tissue injury and you can better assess the tissue."
ESD is now commonly used to treat premalignant and early-stage malignant lesions of the stomach, colorectum and esophagus, according to Louis M. Wong Kee Song, M.D., a gastrointestinal endoscopist at Mayo Clinic's campus in Minnesota.
"Lesions we were not able to resect in the past, we now can remove effectively with ESD," he says. "For example, rectal polyps growing at the dentate line were once only within the purview of the surgeon, but with ESD, we can resect low-lying rectal lesions in intimate contact with the dentate line en bloc as effectively as surgery. Thus, many patients with these lesions are now referred to gastroenterologists for endoscopic resection."
Timothy A. Woodward, M.D., who specializes in gastrointestinal endoscopy at Mayo Clinic's campus in Florida, says success with more-aggressive approaches in the rectum has led to increasing use of endoscopic resection in the duodenum. He was lead author of a study published in Gastrointestinal Endoscopy in 2016 describing deep-tissue en bloc resection of a duodenal carcinoid.
Boundary of lesion
Thermal marking of the boundary of the lesion
Resection defect following endoscopic submucosal dissection
En bloc resected specimen
Distal rectal polypoid lesion
Large 6 cm distal rectal polypoid lesion in intimate contact with the dentate line
"Previously, there was a great deal of emphasis on trying to be more conservative with resections because of concern about perforation, but now we feel we have more latitude. We have experience successfully managing perforations in the colon and rectum, and now, with the availability of full-closure thickness devices, we are more comfortable pushing the envelope. We are resecting more duodenal lesions every year and becoming more aggressive in pursuing very large lesions."
Dr. Fukami, too, says that success with ESD began with the removal of large lesions, including gastric cancers 5 to 10 cm or greater and multifocal esophageal neoplasms resected as long as 18 cm.
"Depending on the situation, size is not the exclusion criteria, but rather whether the tumor depth is within the arena of endoscopic therapy. The goal is curative resection, but that can be very difficult to judge before removal. We focus on complete oncologic resection, aiming for a cure, and then assess the likelihood that the cancer has spread to the lymph nodes. Resection helps decide whether the patient needs more-invasive surgical interventions or can be cured by endoscopy. We are aiming for a cure rate comparable to surgery."
Head-to-head comparisons of ESD and surgical resection are limited. One large retrospective series from the National Cancer Center Hospital in Tokyo, published in Endoscopy in 2012, compared outcomes in nearly 600 patients who underwent either ESD for superficial submucosal invasive colorectal cancer or laparoscopic-assisted colorectal surgery (LAC) for T1 tumors.
The en bloc and curative resection rates for ESD were 87 percent and 80 percent, respectively — comparable to surgical outcomes. ESD was also associated with shorter procedure times and hospital stays and a lower complication rate compared to LAC.
"There is indeed data that some submucosally invasive cancers can be cured by endoscopic resection only, but separating mucosal from submucosal cancers can be difficult prior to removal," Dr. Fukami says. "If the cancer has not invaded the muscularis propria, we tend to remove it for pathological examination. If it is a cancer with no invasion or very limited invasion into the submucosa with no other poor prognostic factors and was caught early enough, the resection can be declared curative. But if malignant invasion deep into the submucosa is suspected, then endoscopic resection is not a suitable option."
ESD is technically demanding and has a higher rate of adverse events such as bleeding, perforation and esophageal stricture than do other endoscopic procedures, including EMR. Intraprocedural bleeding is expected and can usually be managed endoscopically, and almost all perforations are amenable to endoscopic therapy.
Other limitations of ESD include its significant technical challenges and the lack of training programs for it. Perforation rates as high as 6 percent have been reported in the hands of experienced endoscopists, and proper training is essential for the successful implementation of ESD into clinical practice.
"Standardized training programs are well-established in Japan, and we are trying to implement them in the U.S.," Dr. Fukami says. "Compared with EMR, ESD has higher rates of en bloc and curative resections and lower rates of local recurrence. Furthermore, oncological outcomes compare favorably with surgical interventions, and in most cases, this is an outpatient procedure. So these days, everyone wants to learn this technique, but who is going to teach them and how is the current issue in the U.S.?"
For more information
Milano RV, et al. Deep tissue en bloc resection of duodenal carcinoid with combined banding device and over-the-scope-clip. Gastrointestinal Endoscopy. In press.
Kiriyama S, et al. Comparison of endoscopic submucosal dissection with laparoscopic-assisted colorectal surgery for early-stage colorectal cancer: A retrospective analysis. Endoscopy. 2012;44:1024.