PROPER MUSCLE LAYER DAMAGE AFFECTS ULCER HEALING … · 2014. 10. 17. · REFERENCES! [1] Goto O et...

REFERENCES [1] Goto O et al. Short-term healing process of artificial ulcers after gastric endoscopic submucosal dissection. Gut Liver 2011; 5: 293-297 [2] Kobayashi M et al. Contributing factors to gastric ulcer healing after endoscopic submucosal dissection including the promoting effect of rebamipide. Dig Dis Sci. 2012;57:119-126 [3] Kakushima N et al. Histopathologic characteristics of gastric ulcers created by endoscopic submucosal dissection. Endoscopy 2006;38:412-5 [4] Takeuchi K et al. Studies on the fine vessels in the healing process of acetic acid ulcer in the rat stomach. Jpn J Gastrienterol 1983;80:9-15

Yohei Horikawa* , Hiroya Mizutamari, Nobuya Mimori, Yuhei Kato, Kazuhiro Shimazu, Syunji Ohkubo!Gastroenterology, HIRAKA GENERAL HOSPITAL, Yokote city, Japan!

INTRODUCTION: Endoscopic submucosal dissection (ESD) is the established therapy for superficial gastrointestinal neoplasms. As the larger ulcers associated with ESD, management of artificial ulcers has become more important. However, the relationship between ulcer healing factors and treatment is still unclear. 

AIMS & METHODS: We aimed to evaluate the ESD-related artificial ulcer reduction ratio at 4 weeks to assess the factor associating with ulcer healing after ESD that may lead to optimal treatments.  Between January 2009 and December 2013, a total of 375 lesions fulfilled the expanded criteria for ESD. After exclusion, 328 lesions were divided into two groups based on the ulcer reduction rate and analyzed: Group A, rate <90% and Group B, rate ≥90%. These two groups were compared based on clinicopathological /endoscopic features, concomitant drugs, and treatments.

PROPER MUSCLE LAYER DAMAGE AFFECTS ULCER HEALING AFTER GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION

RESULTS: The ulcer reduction rate was significantly correlated with factors related to the ESD procedure, i.e., procedure time,  submucosal fibrosis, and exposure of the proper muscle layer, in univariate analysis. Multivariate logistic regression analysis showed that submucosal fibrosis (F2) (p = 0.03; OR, 16.46; 95% CI, 1.31–206.73) and exposure of the proper muscle layer (p = 0.01; OR, 4.27; 95% CI, 2.04–8.92) were statistically significant predictors of delayed healing.

DISCUSSION: The etiology of artificial ulcers after gastric ESD differs from that of peptic ulcers[1]. The healing process of peptic ulcers requires angiogenesis in the granulation tissue at the ulcer base, together with replication of epithelial cells at the ulcer margin, and subsequent re-establishment of glandular architecture[2]. Meanwhile, artificial ulcers were created iatrogenically under the hypoacidic environment by PPI injection and normal mucosal protective mechanisms in the shallow layer of the submucosa . As the inflammation is localized, with minimal damage to the proper muscle layer preserving the remarkable contraction, ESD-induced ulcers rapidly reduce in size for the first few weeks[3]. Therefore, artificial ulcers have a particular healing formation involving strong traction towards the center of the ulcer with a little regenerative mucosa (Figure 1a). On the other hand, persistent electrocautery damage to the proper muscle layer, caused by exfoliating severe fibrosis or deeper  dissection than assumption, can impair the contraction of muscles. As a result, these artificial ulcers share a similar healing formation with UL-III or UL-IV peptic ulcers, characterized by extension of the massive regenerative mucosa towards the center of the ulcer (Figure 1b)[4].  

CONCLUSION: This single-center retrospective study indicated that ESD-induced artificial ulcer healing was affected by submucosal fibrosis and exposure of the proper muscle layer, which induced damage to the contraction of the muscle layer.

We disclosed no conflicts of interest regarding this poster presentation.

Figure 1b. Peptic-ulcer-like healing pattern : regenerative epithelium from ulcer margin with a mild contraction of the mucosa

Figure 1a. Typical artificial ulcer healing pattern : a remarkable contraction of the mucosa with zipper-like regenerative epithelium

Total <90% 90%� P value

SexM 230 27 203 0.6875F 98 10 88

Age<75 146 17 129 0.8522

75� 182 20 162 Hp�status

Positive 325 37 288 1.0000Negative 3 0 3

Concominant drugsNone 227 23 204 0.3381

Antithrombotic 82 10 72NSAIDs 19 4 15

Tumor location 0.0672U 86 14 72M 117 15 102L 125 8 117

Tumor circumferenceAnterior wall 75 10 65 0.7298Posterior wall 124 15 109

Lesser curvuture 74 8 66Greater curvuture 55 4 51

Macroscopic typeProtruded 17 1 16 0.6798

Flat 177 23 154Depressed 109 10 99Combined 25 3 22

Hp. Helicobacter pylori

Table 2a. Baseline characteristics of included gastric ESD patients and tumors

Reduction rate of ulcer

Total <90% 90%� P value

Procedure time (min)<60 161 12 149 0.0315

60� 167 25 142 Initial ulcer size (mm2)

<900 142 19 123 0.5434900-2500 138 14 1242500� 48 4 44

Submucosal fibrosisF0 245 21 224 0.0009

F1 80 14 66F2 3 2 1

Exposure of proper muscle layerAbsence 268 21 247 0.0000

Presence 60 16 44

Reduction rate of ulcer

Table 2b. Potential risk factors related to the ESD procedure

Total <90% 90%� P value

Histological typeAdenoma 88 11 77 0.6198

Differentiated 119 22 197Undiffernetiated 15 3 12

Other 6 1 5 Tumor depth

M 306 32 274 0.0789SM 22 5 17

Hematemesis on 2nd look endoscopyAbsence 148 18 130 0.6472Presence 180 19 161

Burning of ulcer surfaceB0 215 20 195 0.1188B1 102 14 88B2 11 3 8

Exposed vesselsForrest 2a 115 15 100 0.4583Forrest 2b 213 22 191

Anti-secretory drugs (PPIs)omeprazole 215 22 193 0.0736rabeprazole 41 2 39

esomeprazole 72 13 59

PPIs. Proton pump inhibitors

Reduction rate of ulcer

Table 2c. Potential risk factors after the ESD procedure

P value

Submucosal fibrosis F2 0.0301

Exposure of proper muscle layer Presence 0.0001

CI. confidence interval

Table 3. Risk factors related to post-ESD ulcer reduction

Odds ratio ( 95% CI )

16.46 ( 1.31-206.73 )

4.27 ( 2.04-8.92 )