CASE REPORT
Nagoya J. Med. Sci. 85. 134–140, 2023
doi:10.18999/nagjms.85.1.134

Successful prevention of stenosis after circumferential
endoscopic resection of esophageal cancer
Hitoshi Tanaka, Naomi Kakushima, Koichi Muroi, Takashi Hirose,
Tomohiko Suzuki, Takahiro Suzuki, Emiko Hida, Keiko Hirai,
Hiroyuki Shibata, Nobuhito Ito, Satoshi Furune, Kazuhiro Furukawa
and Mitsuhiro Fujishiro
Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine,Nagoya, JapanABSTRACT
Circumferential resection of a >5-cm longitudinal mucosal defect following esophageal endoscopic
submucosal dissection (ESD) is a risk factor for refractory stenosis. Circumferential ESD was performedin 3 patients with 64, 69, and 70 mm longitudinal mucosal defects. A local steroid injection was used
to treat the postoperative ulcer, followed by an oral steroid. In all three cases, the ulcer healed without
the need for endoscopic dilation. A combination of local injection and oral steroids effectively prevented
esophageal stenosis in patients with high-risk stenosis after ESD.
Keywords: endoscopic submucosal dissection, esophagus, stenosis
Abbreviations:
ESD: endoscopic submucosal dissection
PGA: polyglycolic acid
This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

INTRODUCTION
Endoscopic submucosal dissection (ESD) is widely used to treat early-stage esophageal cancer.1
However, while treating widespread lesions with ESD, post-ESD stenosis is a serious complication.
Endoscopic balloon dilation and steroid administration have been reported to reduce the incidence ofstenosis; however, these preventive measures are not standardized. Moreover, refractory stenosis occurs in cases where circumferential resection of a >5-cm longitudinal mucosal defect is performed.2
We herein report three cases of circumferential ESD of a >5-cm longitudinal mucosal defectfor a widespread lesion, in which stenosis was prevented using a combination of a local steroid
injection and an oral steroid.
Received: December 15, 2021; accepted: February 24, 2022
Corresponding Author: Naomi Kakushima, MD, PhDDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine,
65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
Tel: +81-52-744-2172, Fax: +81-52-744-2180, E-mail: nk202004@med.nagoya-u.ac.jp134

No stenosis after endoscopic resection

CASE REPORT
Case 1A man in his 60’s underwent ESD for a circumferential 0-IIc lesion located in the middle
thoracic esophagus (25–30 cm from incisura) (Fig. 1A). A Splash-M knife® (HOYA Corp,Pentax, Tokyo, Japan) was used for ESD. Successful en bloc resection was performed without
any complications (Fig. 1B). The excised specimen measured 64 mm in length, and a circum-Fig. 1 Case 1
Fig. 1A: A circumferential 0-IIc lesion in the middle thoracic esophagus.
Fig. 1B: Endoscopic submucosal dissection (ESD) was performed without complications, and a circumferentialulcer was observed at 25–33 cm from the incisura.
Fig. 1C: After local injection of 80 mg of triamcinolone acetonide, a polyglycolic acid (PGA) sheet covering
was performed.
Fig. 1D: One week after ESD, the PGA sheet almost fell off at the anal side of the ulcer.
Fig. 1E: At 8 weeks, a circumferential scar was observed, and the endoscope passed through without resistance.
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ferential ulcer was observed at 25–33 cm from the incisura. For the ulcer caused by ESD, 80
mg of triamcinolone acetonide dissolved in saline was injected into the residual submucosal
tissue in 1–2 mg increments. After injection, the ulcer was covered with a polyglycolic acid
(PGA) sheet (Neoveil, Gunze Co, Kyoto, Japan) with fibrin glue (Beriplast P combi-set, CSL
Behring Pharma, Tokyo, Japan) (Fig. 1C). On postoperative day 2, a soft meal was introduced,along with 30 mg of oral prednisolone, which was gradually reduced by 5–10 mg/week over 8weeks. Pathological examination revealed a moderately differentiated squamous cell carcinoma,
pT1a-LPM, ly0, v0, 60 mm, with negative carcinoma margins. Esophagoscopy performed 1 week
after ESD revealed that the PGA sheet had almost fallen off the ulcer caused by ESD (Fig. 1D).
The patient experienced mild dysphagia during the post-ESD course, but he ate normal food. At
8 weeks after ESD, esophagoscopy revealed complete scarring of the ulcer and passage of theendoscope (9.9 mm diameter) through the lumen (Fig. 1E). Endoscopic dilation was not required
during the pos-ESD course.
Case 2A man in his 60’s underwent ESD for a circumferential 0-IIc lesion located in the lower
thoracic esophagus (31–37 cm from incisura) (Fig. 2A). Successful en bloc resection was per-Fig. 2 Case 2
Fig. 2A: A circumferential 0-IIc lesion in the lower thoracic esophagus.
Fig. 2B: ESD was performed without complications, and a circumferential ulcer was observed at 31–39 cm fromthe incisura.
Fig. 2C: At 8 weeks, a circumferential scar was observed, and the endoscope passed through without resistance.
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No stenosis after endoscopic resection

formed without any complications (Fig. 2B). The excised specimen measured 69 mm in length,
and a circumferential ulcer was observed at 31–39 cm from the incisura. To treat the ulcer
caused by ESD, 80 mg of triamcinolone acetonide was injected immediately after the procedure,and 30 mg of oral prednisolone was started on postoperative day 2 as in case 1. Pathologicalexamination revealed well-differentiated squamous cell carcinoma, pT1a-LPM, ly0, v0, 55 mm,with negative carcinoma margins. The patient did not have any symptoms during the post-ESD
course, and complete scarring of the ulcer was observed at 8 weeks without stenosis (Fig. 2C).
Case 3A man in his 50’s underwent ESD for a circumferential 0-IIc located in the lower thoracic
esophagus (30–35 cm from the incisura) (Fig. 3A). Successful en bloc resection was performed
without any complications (Fig. 3B). The excised specimen measured 70 mm in length, and acircumferential ulcer was observed at 30–37 cm from the incisura. The patient received a local
injection of 80 mg of triamcinolone acetonide and 30 mg of oral steroid as in cases 1 and 2.
Pathological examination revealed a well-differentiated squamous cell carcinoma, pT1a-LPM, ly0,v0, 60 mm, with negative carcinoma margins. The patient did not have any symptoms during thepost-ESD course, and complete scarring of the ulcer was observed at 8 weeks without stenosis(Fig. 3C).

Fig. 3 Case 3
Fig. 3A: A circumferential 0-IIc lesion in the lower thoracic esophagus.
Fig. 3B: ESD was performed without complication and a circumferential ulcer was observed at 30–37 cm fromthe incisura.
Fig. 3C: At 8 weeks, a circumferential scar was observed, and the endoscope passed through without resistance.

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DISCUSSION
The incidence of stenosis is high after an esophageal ESD of mucosal defects covering ≥3/4 ofthe circumference of the esophagus.3,4 To prevent post-ESD stenosis, the use of local injection5 ororal steroids,6 balloon dilation,7 stentings,8 and PGA sheet covering9 has been reported; however,these methods are not standardized, and their effects are not fully characterized. Multiple sessionsof preventive endoscopic balloon dilation (EBD) are required to prevent stenosis in high-riskpatients. The optimal time to start EBD after ESD and the interval between EBD sessions areunknown. The use of steroid is known to reduce the incidence of stenosis; however, whether injection or oral steroid is better, or both, and the optimal amount of steroid required are unknown.
Furthermore, even after using these preventive methods, stenosis after a total circumferential ESD
is frequently intractable. One reason for this could be that after circumferential resection, thelength of the ESD ulcer increases due to contraction of the muscularis mucosa of the remaining
oral and anal side mucosa.
In the first case, a combination of local injection, oral steroid, and PGA sheet covering
was used. Although a previous study reported that this method was less effective in preventing
stenosis if the PGA had fallen off at 1 week after ESD,10 the PGA could provide cytoskeletonand carry medicine to accelerate cell repair and wound healing. Histopathological assessment inan animal study revealed that ulcers covered with the PGA sheet had a thick layer containing
fibrin glue and necrotic substances, abundant newly formed blood vessels, and good granulation
at 1 week after the surgery, without excessive inflammation, necrosis, or infection.11 A local
steroid injection has a risk of perforation.12 Thus, it is preferable to avoid multiple injections
during the post-ESD course. The combination of steroid injection and PGA has been exploredin previous studies but was not fully effective.13 The use of a PGA sheet containing fibrin gluein combination with injection and oral steroid therapy has not been explored in previous studies.
Therefore, further studies are required to confirm the effect of this triple combination therapy.
Kadota et al reported a stenosis rate of 71% in patients with an entire circumferential mucosal
defect after ESD using a local injection of 50 mg of triamcinolone acetonide followed by anoral steroid.3 Yamaguchi et al reported a stenosis rate of 33% using an oral steroid for a longer
period (16–18 weeks).14 Systemic steroid therapy for a long period has a risk of serious adverse
events, such as infection.
In our previous study, the rate of post-ESD stenosis in patients with mucosal defects covering≥3/4 but not entire circumference tended to be higher after local steroid injection (40–80 mg)
alone than after local steroid injection and oral prednisolone (61% and 33%, respectively).15
Those who did not receive any steroid treatment developed stenosis and were treated with
EBD. Three patients with entire circumferential mucosal defect received only injection, and one
patient with entire circumferential mucosal defect received 40 mg of local injection with an oral
steroid. All these 4 patients developed stenosis that required multiple EBD (unpublished data).
Therefore, we believe that both local injection and oral steroid are required for patients witha ≥3/4 mucosal defect, and the amount of steroid is essential, especially in patients with anentire circumferential mucosal defect. A triamcinolone product available in our hospital contains
40 mg of the active ingredient in one vial; thus, we used two vials (80 mg) in the three cases
presented here. The dose of oral prednisolone was initially set as 0.5 mg/kg/day. The common
factors among the three cases reported here were the combination of 80 mg of triamcinolone
acetonide injection followed by 8 weeks of oral steroid. Although the mechanism of steroids inpreventing stenosis is not fully understood, the anti-inflammation effect is considered to be thecritical factor. Local injection immediately following ESD would exert a strong anti-inflammatory
effect to the locoregional area. The duration of effective blood concentration of triamcinolone
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No stenosis after endoscopic resection

after intramuscular injection is 14–21 days16; however, the duration after submucosal injection isunknown. After esophageal ESD, the ulcer has less submucosal tissue and is more vulnerable tofood and mucus. Therefore, the duration of the effect of local injection is thought to be much
shorter. The combination of local and oral steroids would decrease the repetition of local injection
and the period of oral steroids. We also believe that a higher dose as 80 mg of local injection
effectively suppresses the immediate inflammatory response at the ulcer for a circumferential
ESD of a >5-cm longitudinal mucosal defect.
In conclusion, although the role of PGA in the prevention of stenosis in circumferential ESD
cases still needs to be elucidated, a combination of local injection and oral steroids may be apromising preventive measure.

CONFLICTS OF INTEREST
All authors have no conflicts of interest.

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