UMIN-CTR Clinical Trial

Public title

Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy

Acronym

ENEC study

Scientific Title

Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy

Scientific Title:Acronym

ENEC study

Region

Japan

Condition

early esophageal squamous cell carcinoma

Classification by specialty

Gastroenterology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Recently, diagnostic technology of gastrointestinal endoscopy, using image enhancement such as magnifying endoscopy, has developed. Accuracy of endoscopic diagnosis for early esophageal squamous cell carcinoma (ESCC) is reported as about 90%. Because endoscopic biopsy sometime causes scar and fibrosis which would make endoscopic resection difficult and because histological diagnosis of minute specimens obtained by biopsy is not always accurate, endoscopic resection for ESCC is now often performed without preoperative endoscopic biopsy in Japan. Accurate technology of endoscopic diagnosis is therefore required.
Recently, high-resolution and ultra-high magnifying (about 500x) videoendoscopy, known as endocytoscopy, that enables microscopic observation at the cellular level has been developed. However, diagnostic ability of endocytoscopy for early esophageal tumor (without biopsy) has not been reported. In this study, we will perform endoscopic surveillance for the patients with high risk of ESCC by using endocytoscopy. The aim of this study is to confirm the accuracy of optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Sensitivity of endoscopic diagnosis by using endocytoscopy.

Key secondary outcomes

1) Rate of evaluable ultra-high magnifying images.
2) Specificity of endoscopic diagnosis by using endocytoscopy.
3) Accuracy of endoscopic diagnosis by using endocytoscopy.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

90

years-old

>=

Gender

Male and Female

Key inclusion criteria

The study subjects included patients who underwent ER for ESCC or were treated for head and neck cancer at the Hokkaido University Hospital and Keiyukai daini hospital, or were refered to the 2 hospitals for the lesions suspicious for early ESCC. The inclusion criteria of this study were as follows: 1) who have background mucosa with multiple minute iodine unstained areas (high risk group for metachronous ESCC), and 2) written informed consent obtained from the patient.

Key exclusion criteria

Exclusion criteria were as follows: 1) with histological diagnosis of SCC by prior endoscopic biopsy, 2) unsuitability as subjects, 3) age < 20 years, and 4) current pregnancy.

Target sample size

200

Name of lead principal investigator

1st name	Yuichi
Middle name
Last name	Shimizu

Organization

Hokkaido University Hospital

Division name

Division of Endoscopy

Zip code

060-8648

Address

Kita 14 jo, Nishi 5 chome, Kitaku, Sapporo, Japan

TEL

011-716-1161

Email

yshimizu@med.hokudai.ac.jp

Name of contact person

1st name	Masaki
Middle name
Last name	Inoue

Organization

Hokkaido University Hospital

Division name

Department of Gastroenterology

Zip code

060-8648

Address

Kita 14 jo, Nishi 5 chome, Kitaku, Sapporo, Japan

TEL

011-716-1161

Homepage URL

Email

mokomokomomon@gmail.com

Institute

Hokkaido University Hospital

Institute

Department

Personal name

Organization

Self funding

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Hokkaido University Hospital Institutional Review Board

Address

Kita 14 jo, Nishi 5 chome, Kitaku, Sapporo, Japan

Tel

011-706-7924

Email

crjimu@huhp.hokudai.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2019

Year

07

Month

25

Day

URL releasing protocol

None

Publication of results

Published

URL related to results and publications

None

Number of participants that the trial has enrolled

78

Results

Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the (endoscopic surveillance during treatment (ESDT) and 10 (12.8%) (95% CI: 6.9 - 22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining.

Results date posted

2023

Year

08

Month

14

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT.

Participant flow

Patients in whom a diagnosis of pharyngeal SCC was made by endoscopic screening and were scheduled to undergo further detailed endoscopic examination for precise diagnosis and determination of the indication for ER were candidates for this study. Patients with lesions that were suspected to be superficial pharyngeal SCC who were referred to the participating institutions were also included. Detailed endoscopic examination was performed for patients who gave consent for participation in the study. The endoscopic examination was performed by using a GIF-H290Z endoscope (Olympus Medical Systems Corp., Tokyo, Japan) under conscious sedation using pethidine hydrochloride, midazoram or diazepam. White light imaging (WLI) and NBI (with magnification) were performed for precise diagnosis of the indication for ER and to determine whether the presence or absence of other pharyngeal lesions in that examination. Laryngoscope and a physical examination were also performed by an otolaryngologist. The valsalva method was used for observation of the postcricoid area4. Patients with lesions that were diagnosed to be confined to the subepithelial layer and with indication for ER were finally enrolled in this study.
The following patients were excluded from this study: (1) patients who had history of total laryngectomy, (2) patients with recurrent or residual pharyngeal SCC after radiotherapy or chemoradiotherapy, (3) patients with a history of allergy for iodine, (4) patients who did not have a sufficient understanding after receiving an explanation for participation in this study, and (5) patients who the investigator considered were unsuitable as subjects.

Adverse events

None

Outcome measures

The primary endpoint was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT (per patient analysis). The secondary endpoints were the additional advantage of lugol staining compared with NBI observation and safety of lugol staining on the pharyngeal mucosa.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2019

Year

05

Month

01

Day

Date of IRB

2019

Year

06

Month

04

Day

Anticipated trial start date

2019

Year

06

Month

20

Day

Last follow-up date

2020

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Patients who are included in this study undergo endoscopic surveillance by using endocytoscopy. If esophageal lesions suspicious for early squamous cell carcinoma (redness area in white light, brownish area in narrow band imaging or demarcated unstained area in iodin staining) are found, endoscopists immediately perform ultra-high magnifying observation (with dyeing of 1% methylene blue solution and 0.05% crystal violet solution) for the lesion. Patients who are diagnosed to have ESCC by using endocytoscopy will undergo endoscopic resection later. Patients who are diagnosed to have benign lesion by using endocytoscopy undergo ordinal endoscopic biopsy. All procedure will be performed by endoscopists who are examined for diagnosis of early ESCC.
Final histological diagnosis will be decided in Sapporo Kosei Hospital as the central review. All specimens will be diagnosed to squamous cell carcinoma (including high grade intraepithelial neoplasia), low grade dysplasia and non-tumor (inflammation, epithelial atrophy) according to WHO classification.

Registered date

2019

Year

07

Month

15

Day

Last modified on

2023

Year

08

Month

14

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042614