Therapeutic outcomes of endoscopic submucosal dissection of differentiated early gastric cancer in a Western endoscopy setting (with video)

doi:10.1016/j.gie.2015.03.1960

Gastrointestinal Endoscopy

Volume 82, Issue 5, November 2015, Pages 804-811

https://doi.org/10.1016/j.gie.2015.03.1960 Get rights and content

Background

Large multicenter gastric cancer endoscopic submucosal dissection (ESD) studies conducted at major Japanese institutions have reported en bloc resection, en bloc tumor-free margin resection, and curative resection rates of 92.7% to 96.1%, 82.6% to 94.5%, and 73.6% to 85.4%, respectively, with delayed bleeding and perforation rates of 0.6% to 6.0% and 3.6% to 4.7%, respectively. Although ESD is currently an alternative treatment in some countries, particularly in Asia, it remains uncertain whether ESD therapeutic outcomes in Western endoscopy settings can be comparable to those achieved in Japan.

Objective

To evaluate the ESD therapeutic outcomes for differentiated early gastric cancer (EGC) in a Western endoscopy setting.

Design/Setting

Consecutive case series performed by an expertly trained Western endoscopist.

Patients

Fifty-three patients with 54 lesions.

Interventions

ESD for early gastric cancers (T1) satisfying expanded inclusion criteria.

Main Outcome Measurements

En bloc resection, en bloc tumor-free margin resection, and curative resection rates were 98%, 93%, and 83%, respectively. The delayed bleeding rate was 7%, and the perforation rate was 4%.

Results

The mean patient age was 67 years, and the mean tumor size was 19.8 mm, with 54% of the lesions located in the lesser curvature. The median procedure time was 61 minutes, with ESD procedures 60 minutes or longer associated with submucosal fibrosis (P < .001) and tumor size 25 mm or larger (P = .03). In every ESD procedure, both circumferential incision and submucosal dissection were performed by using a single knife. Two of the 4 delayed bleeding cases required surgery, and all perforations were successfully managed by using endoscopic clips.

Limitation

Long-term outcome data are currently unavailable.

Conclusion

ESD for differentiated EGC resulted in favorable therapeutic outcomes in a Western endoscopy setting comparable to those achieved at major Japanese institutions.

Section snippets

Background

Gastric cancer ranks as the most common malignant tumor in East Asia, Eastern Europe, and parts of Latin America.¹ Although the incidence and mortality have decreased in the United States over the past 35 years, it is estimated that the disease will be diagnosed in approximately 21,600 Americans and that 10,990 will die of the disease in 2014.² As in many other Latin American countries, gastric cancer is the main cause of cancer-related deaths in Colombia, with an estimated 7700 new cases every

Patients and institutions

A total of 54 differentiated EGCs in 53 consecutive patients were treated in Bogotá by ESD at either the EmuraCenter LatinoAmerica or Clínica Universitaria Colombia from October 2007 to September 2014. The EmuraCenter has served as a reference facility since 2007, where highly qualified local and Japanese endoscopists have provided training in specific endoscopic techniques such as narrow-band imaging,¹¹ magnifying colonoscopy,¹² ESD,13, 14 and systematic alphanumeric coded endoscopy (SACE).¹⁵

Clinicopathological characteristics

The mean patient age was 67 years (range 45-89 years), and the male:female ratio was 1.1:1. Lesions were located in the pyloric channel, antrum, angulus, lower third, middle third, and upper third in 7%, 41%, 15%, 11%, 11%, and 15% of the cases, respectively. Regarding cross-sectional position on the circumference, most of the 50 lesions, exclusive of the 4 lesions involving the pyloric channel, were located in the lesser curvature (58%, 29/50) followed by the anterior (16%, 8/50) and posterior

Discussion

Despite the increasing use of endoscopic procedures for the treatment of early GI malignancies, there have been only a few previously published reports on therapeutic outcomes of ESD for EGC in Western countries.27, 32 Although it has been speculated that Western institutions could not achieve ESD results comparable to those at Japan institutions,32, 33 the findings of this study demonstrate favorable outcomes similar to those achieved at major Japanese institutions.

The Western delay in

References (52)

T. Gotoda et al.
Is en bloc resection essential for endoscopic resection of GI neoplasia?
Gastrointest Endosc
(2008)
Z.H. Henry et al.
Meshed capillary vessels found on narrow-band imaging without optical magnification effectively identifies colorectal neoplasia: a North American validation of the Japanese experience
Gastrointest Endosc
(2010)
O.M. Canales et al.
Usefulness of the Exera magnifying NBI system for differential diagnosis of small colorectal polyps using the Sano-Emura classification in Peru [abstract]
Gastrointest Endosc
(2011)
A.Y. Wang et al.
Endoscopic submucosal dissection with electrosurgical knives in a patient on aspirin therapy (with video)
Gastrointest Endosc
(2010)
T. Uraoka et al.
Effectiveness of glycerol as a submucosal injection for EMR
Gastrointest Endosc
(2005)
T. Kitamura et al.
Argon plasma coagulation for early gastric cancer: technique and outcome
Gastrointest Endosc
(2006)
B. Schumacher et al.
Endoscopic submucosal dissection of early gastric neoplasia with a water jet-assisted knife: a Western, single-center experience
Gastrointest Endosc
(2012)
H. Neuhaus
ESD around the world: Europe
Gastrointest Endosc Clin N Am
(2014)
F. Iacopini et al.
Stepwise training in rectal and colonic endoscopic submucosal dissection with differentiated learning curves
Gastrointest Endosc
(2012)
P. Llorens
Gastric cancer in Chile
Gastrointest Endosc
(1999)

F. Emura et al.

The pharynx: examination of an area too often ignored during upper endoscopy

Gastrointest Endosc

(2013)

P.V. Draganov et al.

Techniques of endoscopic submucosal dissection: application for the Western endoscopist?

Gastrointest Endosc

(2013)

J.C. Park et al.

How to manage pyloric tumours that are difficult to resect completely with endoscopic resection: comparison of the retroflexion vs. forward view technique

Dig Liver Dis

(2011)

T.H. Baron et al.

A comprehensive approach to the management of acute endoscopic perforations (with videos)

Gastrointest Endosc

(2012)

K.D. Crew et al.

Epidemiology of gastric cancer

World J Gastroenterol

(2006)

A snapshot of stomach cancer. Incidence and mortality. Available at: www.cancer.gov/researchandfunding/snapshots....

R. Murillo et al.

Atlas de mortalidad por cáncer en Colombia

(2004)

M. Piñeros et al.

Atlas de mortalidad por cáncer en Colombia

(2010)

I. Oda et al.

Endoscopic submucosal resection for early gastric cancer: technical feasibility, operation time and complications from a large consecutive series

Digest Endosc

(2005)

H. Isotomo et al.

Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study

Gut

(2009)

I. Oda et al.

A multicenter retrospective study of endoscopic resection for early gastric cancer

Gastric Cancer

(2006)

T. Sugimoto et al.

Endoscopic submucosal dissection is an effective and safe therapy for early gastric neoplasms: a multicenter feasible study

J Clin Gastroenterol

(2012)

K. Hotta et al.

A comparison of outcomes of endoscopic submucosal dissection (ESD) For early gastric neoplasms between high-volume and low-volume centers: multi-center retrospective questionnaire study conducted by the Nagano ESD Study Group

Intern Med

(2010)

G. Vargas et al.

Tratamiento endoscópico de cancer gástrico temprano mediante Disección Endoscópica Sub-Mucosa (DES) usando el IT-Knife 2

Rev Gastroenterol Perú

(2012)

F. Emura et al.

Improving early detection of gastric cancer: a novel systematic alphanumeric-coded endoscopic approach

Rev Gastroenterol Perú

(2013)

C.C. Chang et al.

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: an endoscopist-blinded, prospective, randomized study

World J Gastroenterol

(2007)

Cited by (50)

Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort
2023, Clinical Gastroenterology and Hepatology
Citation Excerpt :
Second, the favorable long-term survival of gastric ER in this report may not be representative of the outcomes obtained at all institutions in other countries, including Western countries, because in Japan, the technical skill level for performing gastric ER is relatively high and pathological evaluations for EGC have been standardized according to Japanese guidelines.24 Recently, however, evidence supporting the safety and effectiveness of ER for EGC in Western cohorts has been increasing.25-27 In the future, our findings could be generalized to Western countries.
We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study.
We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C).
Overall, the 5-year OS was 89.0% (95% CI, 88.3%–89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS.
ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).
Wide-field ESD for Barrett's adenocarcinoma at the gastroesophageal junction: technical approaches to facilitate en bloc R0 resection
2022, VideoGIE
Citation Excerpt :
As a result, the counter-traction force of gravity pulled up the lesion allowing a better vision and minimizing the risk of perforation without the use of external traction methods. As reported by the authors here7 and other experts,8,9 when performing marking and mucosal cutting during some ESD procedures, a conventional needle knife is often the preferred tool over other dedicated ESD accessories. Advantages of using a needle knife include reusability, blade length adjustment, and low cost.
Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America
2021, Clinical Gastroenterology and Hepatology
Citation Excerpt :
The pooled rate for perforation was 2.6% and for bleeding was 4.2%.19 Studies from Europe and South America reported en-bloc resection rates of 87%–100%, R0 resection rates of 64%–93%, perforation rates of 0%–10% and bleeding rates of 1%–8%.12,13,15,16,20–22 The resection success rates of our study are slightly lower than those from Eastern studies and comparable to those of other Western studies.
Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America.
We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death.
Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD.
ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.
Outcomes of endoscopic submucosal dissection for early esophageal and gastric cardia adenocarcinomas
2021, Clinics and Research in Hepatology and Gastroenterology
Citation Excerpt :
Our 86% R0 resection rate and 66% curative resection rate for invasive esophageal adenocarcinomas are in line with these results. Similarly, ten studies on ESD for gastric adenocarcinomas have been carried out in Western countries over the past five years [27–37]: the R0 resection rates ranged from 65.6% [30] to 93% [28], and the curative resection rate from 58.7% [36] to 83.2% [32]. A recent meta-analysis assessing histological outcomes after endoscopic resection of early gastric adenocarcinoma in Western countries found that the curative resection rate of early gastric cancer was 72% [37], also consistent with our results (63% for gastric cardia adenocarcinomas).
Adenocarcinomas of the esophagus and of the gastric cardia are regarded as a same clinical entity in oncology. For endoscopic resection however, endoscopic mucosal resection is recommended for esophageal adenocarcinoma, while endoscopic submucosal dissection (ESD) is advocated for gastric adenocarcinomas. Our aim was to compare the outcomes of ESD in both types of esophagogastric junction adenocarcinomas.
Between March 2015 and December 2019, we included all patients who underwent an ESD for early adenocarcinoma of the esophagogastric junction at a French tertiary referral center. Esophageal and gastric cardia adenocarcinomas were compared in terms of clinical, procedural and histological outcomes.
57 esophageal and 19 gastric cardia adenocarcinomas were included in the analysis, for a total of 76 patients. The median (IQR) size of the resections was 40 (40–57.5) and 50 (35–55) mm, p = 0.96, respectively. En bloc resection was achieved in 100% and 89% for adenocarcinomas of the esophagus and the gastric cardia, p = 0.06. Late adverse events occurred in 14% and 5.3%, respectively, p = 0.44, with no severe adverse event. Curative resection rates were 67% and 63% for adenocarcinomas of the esophagus and the gastric cardia, respectively, p = 0.89.
ESD is a safe treatment for T1 adenocarcinomas of the esophagogastric junction, curative in two thirds of the patients, in tumors arising from the esophagus or from the stomach. ESD should be considered for the routine resection of esophageal adenocarcinomas.
AGA Institute Clinical Practice Update: Endoscopic Submucosal Dissection in the United States
2019, Clinical Gastroenterology and Hepatology
Endoscopic submucosal dissection (ESD) is an established endoscopic resection method in Asian countries, which is increasingly practiced in Europe and by early adopters in the United States for removal of early cancers and large lesions from the luminal gastrointestinal tract. The intent of this expert review is to provide an update regarding the clinical practice of ESD with a particular focus on its use in the United States. This review is framed around the 16 best practice advice points agreed upon by the authors, which reflect landmark and recent published articles in this field. This expert review also reflects our experience as advanced endoscopists with extensive experience in performing and teaching others to perform ESD in the United States.
Best Practice Advice 1: Endoscopic submucosal dissection should be recognized as a mature endoscopic technique that enables complete removal of lesions that are too large for en bloc endoscopic mucosal resection or are at increased risk of containing cancer.
Best Practice Advice 2: The safety and feasibility of endoscopic submucosal dissection for early gastric cancer is well established. The absolute indications for curative endoscopic resection include moderately and well-differentiated, nonulcerated, mucosal lesions that are ≤2 cm in size.
Best Practice Advice 3: Other relative (expanded) indications for gastric endoscopic submucosal dissection include moderately and well-differentiated superficial cancers that are >2 cm, lesions ≤3 cm with ulceration or that contain early submucosal invasion, and poorly differentiated superficial cancers ≤2 cm in size. The risk of lymph node metastasis when endoscopic submucosal dissection is performed for these indications is higher than when it is performed for absolute indications but remains acceptably low.
Best Practice Advice 4: Endoscopic submucosal dissection may be considered in selected patients with Barrett’s esophagus with the following features: large or bulky area of nodularity, lesions with a high likelihood of superficial submucosal invasion, recurrent dysplasia, endoscopic mucosal resection specimen showing invasive carcinoma with positive margins, equivocal preprocedural histology, and intramucosal carcinoma.
Best Practice Advice 5: Endoscopic submucosal dissection is the primary modality for treatment of squamous cell dysplasia and cancer confined to the superficial esophageal mucosa. Any degree of submucosal invasion caries an increased risk of lymph node metastasis and alternative/additional therapy should be considered.
Best Practice Advice 6: Duodenal endoscopic submucosal dissection is associated with an increased risk of intraprocedural perforation and delayed adverse events. Duodenal endoscopic submucosal dissection should be limited to endoscopists with extensive experience in performing endoscopic submucosal dissection in other locations. It is strongly suggested that endoscopists in the United States refrain from performing duodenal endoscopic submucosal dissection during the early phase of their endoscopic submucosal dissection practice.
Best Practice Advice 7: All colorectal lesions should be evaluated for suitability for endoscopic resection. Accumulating evidence has shown that the majority of colorectal neoplasms without signs of deep submucosal invasion or advanced cancer can be treated by advanced endoscopic resection techniques.
Best Practice Advice 8: Colorectal neoplasms containing dysplasia confined to the mucosa have no risk for lymph node metastasis and endoscopic resection should be considered as the criterion standard.
Best Practice Advice 9: Large (>2 cm) colorectal lesions frequently (>43%) require piecemeal removal when endoscopic mucosal resection is used, which is associated with increased (up to 20%) rates of recurrent neoplasia. Endoscopic submucosal dissection enables higher rates of en bloc resection and lower recurrence rates for these lesions. Patients with large complex colorectal polyps should be referred to a high-volume, specialized center for endoscopic removal by endoscopic mucosal resection or endoscopic submucosal dissection.
Best Practice Advice 10: Endoscopic resection for colorectal lesions offers significant cost benefit compared with surgery, and case-based endoscopic submucosal dissection selection for high-risk lesions could offer cost savings.
Best Practice Advice 11: Endoscopists in the United States embarking on performing endoscopic submucosal dissection should be familiar with currently available endoscopic tissue closure devices. Both clip closure and endoscopic suturing techniques have been shown to be effective in managing intraprocedural perforation. Complete closure of a post–endoscopic submucosal dissection site may be considered in certain circumstances based on patient factors, procedural factors, and the location of the lesion.
Best Practice Advice 12: Careful coagulation of exposed blood vessels in the resection site may reduce the risk of delayed bleeding after endoscopic submucosal dissection. The use of low-voltage coagulation current is recommended for this technique.
Best Practice Advice 13: Endoscopists should affix the endoscopic submucosal dissection specimen to a flat surface (eg, pin the specimen to cork board) and immerse it in formalin. An expert gastrointestinal pathologist should evaluate the specimen for margin involvement, degree of differentiation, presence or absence of lymphovascular invasion, depth of submucosal invasion (if present), and tumor budding.
Best Practice Advice 14: Acquiring high-level competency in endoscopic submucosal dissection is achievable in the United States. Alternative educational models should be used in the United States because of the limited number of experts and the differing prevalence of gastrointestinal luminal diseases as compared with Asia.
Best Practice Advice 15: The endoscopic submucosal dissection educational model most suited for the current environment in the United States is a stepwise approach consisting of didactic self-study, attending training courses with increasing levels of complexity, self-practice on animal models, and observation of live cases performed by experts. Endoscopists should perform their initial endoscopic submucosal dissections on patients with lesions that have well-established indications for endoscopic submucosal dissection and are of the lowest technical complexity.
Best Practice Advice 16: Endoscopists in the United States who perform endoluminal resection should educate referring physicians to avoid practices that may induce submucosal fibrosis hampering future endoscopic mucosal resection or endoscopic submucosal dissection. These practices include tattooing in close proximity to or beneath a lesion for marking and partial snare resection of a portion of a lesion for histopathology.
Endoscopic Submucosal Dissection: Indications and Application in Western Endoscopy Practice
2018, Gastroenterology
Citation Excerpt :
Skepticism of the efficacy of endoscopic treatment for EGC may also play a role.47 Recent single-center studies demonstrate favorable therapeutic outcomes that are comparable to those achieved in Asian institutions.49–53 Depending on inclusion criteria, the reported rates for en bloc and R0 resection ranged from 89% to 100% and 74% to 93%, respectively.
Endoscopic submucosal dissection was developed in Japan, early in this century, to provide a minimally invasive yet curative treatment for the large numbers of patients with early gastric cancer identified by the national screening program. Previously, the majority of these patients were treated surgically at substantial cost and with significant risk of short- and long-term morbidity. En-bloc excision of these early cancers, most with a limited risk of nodal metastasis, allowed complete staging of the tumor, stratification of the subsequent therapeutic approach, and potential cure. This transformative innovation changed the nature of endoscopic treatment for superficial mucosal neoplasia and, ultimately, for the first time allowed endoscopists to assert that the early cancer had been definitively cured. Subsequently, Western endoscopists have increasingly embraced the therapeutic possibilities offered by endoscopic submucosal dissection, but with some justifiable scientific caution. Here we provide an evidence-based critical appraisal of the role of endoscopic submucosal dissection in advanced endoscopic tissue resection.

View all citing articles on Scopus

: DISCLOSURE: This work was supported in part by a grant-in-aid for the Comprehensive Strategy to Control Cancer in the Americas from the Emura Foundation for the Promotion of Cancer Research. All authors disclosed no financial relationships relevant to this article.

: If you would like to chat with an author of this article, you may contact Dr Emura at [email protected].

View full text

Original articleClinical endoscopyTherapeutic outcomes of endoscopic submucosal dissection of differentiated early gastric cancer in a Western endoscopy setting (with video)

Background

Objective

Design/Setting

Patients

Interventions

Main Outcome Measurements

Results

Limitation

Conclusion

Section snippets

Background

Patients and institutions

Clinicopathological characteristics

Discussion

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc Clin N Am

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Dig Liver Dis

Gastrointest Endosc

Epidemiology of gastric cancer

World J Gastroenterol

Atlas de mortalidad por cáncer en Colombia

Atlas de mortalidad por cáncer en Colombia

Endoscopic submucosal resection for early gastric cancer: technical feasibility, operation time and complications from a large consecutive series

Digest Endosc

Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study

Gut

A multicenter retrospective study of endoscopic resection for early gastric cancer

Gastric Cancer

Endoscopic submucosal dissection is an effective and safe therapy for early gastric neoplasms: a multicenter feasible study

J Clin Gastroenterol

A comparison of outcomes of endoscopic submucosal dissection (ESD) For early gastric neoplasms between high-volume and low-volume centers: multi-center retrospective questionnaire study conducted by the Nagano ESD Study Group

Intern Med

Tratamiento endoscópico de cancer gástrico temprano mediante Disección Endoscópica Sub-Mucosa (DES) usando el IT-Knife 2

Rev Gastroenterol Perú

Improving early detection of gastric cancer: a novel systematic alphanumeric-coded endoscopic approach

Rev Gastroenterol Perú

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: an endoscopist-blinded, prospective, randomized study

World J Gastroenterol

Original article
Clinical endoscopy
Therapeutic outcomes of endoscopic submucosal dissection of differentiated early gastric cancer in a Western endoscopy setting (with video)