COmpletion Sentinel Node Resection With or Without Minimally invAsive and Endoscopic Cooperative Surgery Following noncuRative Endoscopic Submucosal Dissection for Early Gastric Cancer
Phase: NA
Conditions: Early Gastric Cancer
Sponsor: Region Stockholm

COmpletion Sentinel Node resection with or without minimally 
invAsive and endoscopic cooperative surgery following non-
cuRative Endoscopic Submucosal Dissection for Early Gastric Cancer 
(Co-SNARE-EGC trial)
Background
Early gastric cancer (EGC) is defined as a tumor confined to the mucosa or submucosal layers
without lymph node involvement  (1).  Patients with EGC are typically recommended 
endoscopic submucosal dissection (ESD) as the first-line treatment, provided they meet the 
inclusion criteria. The current expanded indications for ESD in EGC include differentiated 
cancer without ulceration, regardless of size; differentiated cancer with ulceration, provided 
the lesion is no larger than 3 cm; and undifferentiated cancer without ulceration, with a 
maximum size of 2 cm(2,3). In some cases, patients may be classified as non-curative 
(eCuraC2) after ESD due to positive vertical margins, deep submucosal invasion, or 
lymphovascular invasion. In such instances, complementary surgery is generally 
recommended (2,3). Gastrectomy with lymphadenectomy carries a risk of severe 
complications (Clavien-Dindo grade >IIIa) ranging from 8.9% to 22% (4–6), and can 
significantly affect the patient’s health-related quality of life (7). Moreover, many patients 
may have no residual disease after surgery. A recent multi-center Western study found that 
33% of patients who underwent gastrectomy following non-curative ESD had residual tumor,
either locally or in regional lymph nodes (8). 
Local injection of indocyanine green (ICG) into the peritumoral area has been reported in 
gastric cancer surgery to identify sentinel lymph nodes, visualize draining lymph nodes, and 
assess the completeness of lymph node dissection (9). In this phase 1 trial, we aim to 
evaluate ICG-guided regional lymph node resection, including sentinel node (SN) 
identification, with complementary laparoscopic and endoscopic cooperative surgery (LECS) 
as an alternative to gastrectomy following non-curative ESD. For patients with radical but 
non-curative ESD, ICG-guided SN resection will be performed, while in those with non-radical
ESD, LECS combined with ICG-guided SN resection will be performed.
Study design
A single-center, phase-1, prospective non-randomized trial.
Scientific objectives
To study the safety and feasibility of ICG-guided SN with or without additional LECS as an 
alternative treatment for EGC with previous non-curative ESD
Primary outcome measures

Safety, defined as Clavien-Dindo complication grade >/= III 
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Secondary outcome measures

Any complication (Clavien-Dindo II-IV) 

Postoperative bleeding requiring blood transfusion

Leakage/postoperative abscess requiring drainage

Operation time

pT 

Radicality

Number of lymph nodes

Number of positive lymph node

Hospital-stay

Health-related quality of life

30-day mortality, 

In-hospital mortality

1-year disease-free survival
Study population
Patients with EGC previously treated with ESD at our institution will be eligible for inclusion 
in the study if the resection is non-curative  
Inclusion criteria

EGC previously treated with ESD according to current guidelines (differentiated 
adenocarcinoma Ulcerative- any size, differentiated adenocarcinoma Ucerative+ 
</=3cm, undifferentiated adenocarcinoma Ucerative- </=2cm)

Non curative resection  
o
LVI positive
o
R1 vertical margin
o
deep submucosal invasion >Sm1

Signed informed consent
Exclusion criteria

Location within 2 cm from cardia or pylorus

Non-curative resection with only R1 horizontal margin

Inoperative because of severe comorbidities

Previous radiotherapy to the upper abdomen

Pregnancy

Allergy to ICG

Inability to provide informed consent due to cognitive impairment, language barrier, 
or other reasons impairing understanding and autonomous decision-making.
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The procedure
ICG-guided sentinel node (SN) resection will be performed by endoscopically injecting 0.5 ml 
of 100-fold diluted ICG at four sites around the tumor scar, followed by resection of the 
positive lymph nodes after a 15-20 minutes waiting period. LECS will be performed through a
combination of endoscopic marking around the scar, dissection using a knife, perforation of 
the gastric wall, and subsequent laparoscopic resection of the area under endoscopic 
guidance.
Study flowchart
ECG
ESD
MDT
Curative
resection
Non-curative
resection
Standard follow-
up
Consideration for 
surgery
Inclusion in the
study
R0 vertical margin, LVI
positive or Sm-invasion
R1 vertical margin
LECS + ICG-guided
SN
ICG-guided SN
MDT
follow-up
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Preo
p 
visit
ICG 
guide
d SN 
+/- 
LECS
Posto
p visit 
(30 
days)
3 months 
postop – 
CT + 
gastroscop
y
6 months 
postop – 
CT + 
gastroscop
y
9 months 
postop – 
CT + 
gastroscop
y
12 months 
postop – 
CT + 
gastroscop
y
Information 
and consent 
form
x
Physical & 
laboratory 
evaluation 
x
x
x
x
x
x
HQL-
questionnaire
s
x
x
x
Review of 
medical charts
x
x
Assessment of safety
Complications will be continuously monitored for each procedure according to the clinic’s 
routines. An interim analysis will be performed for each 3 cases completed. If any death is 
observed directly attributed to the procedure the study will be prematurely 
discontinued. Moreover, the study will also be discontinued if severe complications (Clavien-
Dindo complication grade ≥ III) are observed in > 20 % of cases, which is the expected rate 
for gastrectomy (6).
Follow-up
All patients will undergo an initial postoperative follow-up at the outpatient clinic 30 days 
after the procedure. Subsequent follow-up visits will occur every 3 months during the first 
year. During this period, surveillance will include both endoscopic (gastroscopy) and 
radiological (computed tomography) assessments at 3-month intervals. After the first year, 
patients will be followed according to the clinic’s standard protocol, consisting of physical 
examination, radiological imaging, and endoscopic evaluation every 6 months for a total 
follow-up period of 5 years. For patients who die before completing follow-up, the date of 
death will be documented.
Sample size
We aim to include 10 patients in the study.
Sample size justification
Because this is a pilot study no power calculation is deemed necessary.
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Management of data
Information and data from patients included in the study will be handled only by researchers
working under confidentiality according to the Health and Healthcare Act. The data will be 
collected in a database and pseudonymized with study-specific patient codes. All study 
documentation will be stored in a locked, protected location intended for handling 
confidential information at Karolinska University Hospital in Stockholm. Only personnel 
delegated for the study as well as the monitor will have, under confidentiality protection, 
access to patient records and source data. The code key in these cases will be handled by the
appointed research coordinator at the Medical Unit of Upper Abdomen, Karolinska 
University Hospital in Stockholm. The data material will be destroyed 10 years after 
publication.
Ethics
The study is conducted in compliance with the protocol and in accordance with the ethical 
principles of the second Declaration of Helsinki and with GCP rules. The EU General Data 
Protection Regulation (GDPR) will be respected. The rights, safety and well-being of the trial 
subjects are the most important considerations and should prevail over the interests of 
science and society. Study personnel conducting this trial are qualified by education, 
training, and experience to perform their respective tasks.
Dissemination of knowledge and publication strategy
The study will be registered at www.clinicaltrials.gov. The protocol will be internationally 
exposed through a separate publication. Positive as well as negative or inconclusive results 
will be submitted for publication in international peer-reviewed journals and oral 
presentations at relevant national and international congresses.
Competing interests 
We declare no support and no financial relationships with any organizations that might have 
an interest in the submitted work.
References
1. Murakami T. Early cancer of the stomach. World J Surg. 1979 Nov;3(6):685–92. 
2. Pimentel-Nunes P, Libânio D, Bastiaansen BAJ, Bhandari P, Bisschops R, Bourke MJ, et 
al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European 
Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2022 
Jun;54(6):591–622. 
3. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer Off J Int 
Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2023 Jan;26(1):1–25. 
2025-09-02
2025-05956-01-834365
Etikprövningsmyndigheten

4. Wang WJ, Li HT, Yu JP, Su L, Guo CA, Chen P, et al. Severity and incidence of 
complications assessed by the Clavien-Dindo classification following robotic and 
laparoscopic gastrectomy for advanced  gastric cancer: a retrospective and propensity 
score-matched study. Surg Endosc. 2019 Oct;33(10):3341–54. 
5. Nevo Y, Goldes Y, Barda L, Nadler R, Gutman M, Nevler A. Risk Factors for 
Complications of Total/Subtotal Gastrectomy for Gastric Cancer: Prospectively Collected, 
Based on the Clavien-Dindo Classification System. Isr Med Assoc J IMAJ. 2018 
May;20(5):277–80. 
6. Tsekrekos A, Vossen LE, Lundell L, Jeremiasen M, Johnsson E, Hedberg J, et al. 
Improved survival after laparoscopic compared to open gastrectomy for advanced gastric 
cancer: a Swedish population-based cohort study. Gastric Cancer Off J Int Gastric Cancer 
Assoc Jpn Gastric Cancer Assoc. 2023 May;26(3):467–77. 
7. van den Boorn HG, Stroes CI, Zwinderman AH, Eshuis WJ, Hulshof MCCM, van Etten-
Jamaludin FS, et al. Health-related quality of life in curatively-treated patients with 
esophageal or gastric cancer: A systematic review and meta-analysis. Crit Rev Oncol 
Hematol. 2020 Oct;154:103069. 
8. Morais R, Libanio D, Dinis Ribeiro M, Ferreira A, Barreiro P, Bourke MJ, et al.: 
Predicting residual neoplasia after a non-curative gastric ESD: validation and modification 
of the eCura system in the Western setting the W-eCura score. Gut. 2023 Dec 7;73(1):105–
17. 
9. Belia F, Biondi A, Agnes A, Santocchi P, Laurino A, Lorenzon L, et al. The Use of 
Indocyanine Green (ICG) and Near-Infrared (NIR) Fluorescence-Guided Imaging in 
Gastric Cancer Surgery: A Narrative Review. Front Surg. 2022;9:880773. 
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