Endoscopic submucosal dissection (ESD) for gastric neoplasms is a widely performed procedure. Local recurrence is rare, but various post-ESD scars are encountered during follow-up endoscopy. Therefore, we investigated atypical scar patterns and evaluated the associated factors.
Clinicopathologic and endoscopic reviews of gastric neoplasms treated with ESD from January 2009 to December 2015 were conducted. Atypical scar patterns were classified as irregular erythema, nodularity, or mucosal defect.
A total of 264 patients with 274 gastric neoplasms, including 201 adenomas and 73 early gastric cancers, were enrolled. The key endoscopic findings at the resection scar were defined on the basis of gross morphology as follows: irregular erythema, mucosal defect (erosion or ulcer), and nodularity. An irregular erythema scar pattern was associated with male sex, a nodularity scar pattern with smoking, and a mucosal defect scar pattern with infra-angle location (angle and antrum) and cancer. An irregular erythema with nodularity scar pattern was also associated with male sex. An irregular erythema with nodularity and mucosal defect scar pattern was associated with liver disease and chronic kidney disease.
The atypical scar patterns after gastric ESD are associated with various clinicopathologic factors.
Gastric cancer is a common malignancy and a major cause of morbidity and mortality worldwide. In East Asia, gastric cancer has shown high mortality rates [
Surgical resection is the standard method of treatment; however, for the treatment of select patients with EGC, a paradigm shift away from surgery to endoscopic resection (ER) is increasingly being seen, because ER is beneficial for the treatment of selective EGC and even gastric adenoma, which is considered a premalignant lesion. ER has shown many advantages over surgical resection in terms of less invasiveness, preservation of organ function, low cost, short hospital stay, and improvement of the quality of life [
To date, there have been few studies focusing on the relationship between risk factors for tumor recurrence and an iatrogenic ulcer scar appearance [
From January 2009 to December 2015, patients who underwent ESD for gastric neoplasms at Chung-Ang University Hospital (Seoul, Korea) were initially enrolled. Gastric adenoma and carcinoma, especially EGC, were categorized as gastric neoplasms in this study. Gastric neoplasm was confirmed with forceps biopsy under esophagogastroduodenoscopy (EGD) guidance (GIF-H260 or GIF-Q260; Olympus, Tokyo, Japan). During EGD, if dysplasia or carcinoma was suspected, two to four biopsy samples were obtained with forceps (FB-25 K-1 [Olympus] or BX 420 [PriMed Instruments Inc., Ontario, Canada]). ESD was indicated when the following criteria were met: any lesions with low- to high-grade dysplasia, regardless of size, or well- to moderately differentiated adenocarcinoma confined to the mucosa without evidence of lymph node or distant metastases on abdominal computed tomography or endoscopic ultrasonography. However, in some patients, the pathological results after ESD were revealed to be outside of the criteria. In such cases, whether to perform additional surgery or ESD was decided according to the physician’s discretion and the patient’s wish. The following patients were excluded from the study: those who had no endoscopy at the 3-month follow-up visit and those who underwent surgical resection after endoscopic treatment owing to adverse events or lymphovascular or margin invasion in the pathological specimen. The medical records of patients were reviewed with regard to age, sex, medication,
Each endoscopic finding and report at 3 months follow-up were reviewed to determine the size, location, macroscopic type, and gross morphology of the lesion. The location of lesions was defined according to seven sections of the stomach: antrum, angle, lower body, mid body, high body, fundus, and cardia. The location of the lesion was classified following the Japanese Classification of Gastric Carcinoma [
In the present study, the key endoscopic findings at the resection scar were defined on the basis of gross morphology, as follows: irregular erythema, mucosal defect (erosion or ulcer), and nodularity (
All lesions were removed through ESD by three experienced gastrointestinal endoscopists (B.J.K., J.G.K., and C.H.C) by using a single-channel endoscope (GIF-Q260J, GIF-H260Z, or GIF-H290; Olympus). The patients were sedated by using a course of intravenous midazolam (0.05 mg/kg) or propofol and remifentanil, with a target-controlled infusion system under bispectral index (BIS) monitoring by an experienced anesthesiologist. The initial target effect-site concentration of propofol and remifentanil was 1.5 μg/mL and 1.5 ng/mL, respectively. The plasma concentration was increased or decreased by 0.2 μg/mL or 0.2 ng/mL, targeting a 60~80 BIS score.
In all patients, dot markings for ESD were first placed 5 mm beyond the tumor margins with argon plasma coagulation. A saline solution (100 mL 0.9% saline mixed with 1 mg epinephrine and a small amount of indigo carmine) was then injected into the submucosal layer, and the submucosal layer around the lesion was dissected by using a needle knife (Nadel-Papillotom, 99020121; MTW Endoskopie, Wesel, Germany), insulated-tip knife (KD-611L; Olympus), and/or flex knife (KD-630L; Olympus). If necessary, saline injection was repeated and endoscopic hemostasis was achieved during the procedure. A high-frequency electrosurgical current generator (VIO 300D; ErbeElektromedizin, Tübingen, Germany) was used during the processes of marking, mucosal incision, submucosal dissection, and hemostasis. A complete resection was defined as a resection in which the resected tumor had tumor-free horizontal and vertical margins. Complete
After ESD, all patients received 40 mg pantoprazole intravenously or took 30 mg lansoprazole orally once daily on the day they underwent ESD and throughout the length of their hospital stay, which was usually 4~5 days. If no ESD-related adverse events occurred, the patients were allowed a liquid diet on the first or second day after ESD. The patients were discharged the day after starting diet. After discharge, the patients were instructed to take 30 mg lansoprazole once a day for 4 weeks. The patients were examined with conventional endoscopy at 3, 6, and 12 months after ER and annually thereafter.
At our center, pathologic diagnosis was made on the basis of the third edition of the Japanese Classification of Gastric Carcinoma [
Statistical analysis was performed with SPSS ver. 21.0 (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL, USA). For univariate analysis, categorical variables were analyzed by using a chi-square test or Fisher exact test. Those variables with
A total of 301 gastric neoplasms were removed by ESD at Chung-Ang University Hospital between January 2009 and December 2015. Among them, 16 were excluded because of follow-up loss, two because of unavailable images at the resection site, eight because of an additional operation, and one because of tissue loss after ER. Therefore, the remaining 274 neoplasms, including 201 adenomas and 73 EGCs, were finally enrolled (
The baseline clinicopathologic characteristics of the study population are summarized in
Among the total lesions resected by using ESD, 201 were adenomas and 73 were EGCs. Almost lesions were located at the antrum or angle, and the macroscopic shape of most lesions was superficially elevated. The mean size of the tumor was 14.6 mm, and the mean area of the tumor was 212.4 mm2. The
Therapeutic outcomes are summarized in
Atypical scar patterns were defined as irregular erythema, nodularity, or mucosal defect. In univariate analysis for the irregular erythema scar pattern, the following factors showed marginal significance (
Although follow-up endoscopy usually detects a hypertrophied and/or hyperemic scar at the ER site, it is not known whether these findings are suggestive of local recurrence. A recent study reported that several typical endoscopic findings such as irregular erythema, nodularity, mucosal defect, and a combination of these patterns might predict the local recurrence after ESD for EGCs [
In the early days since ER had been introduced, concerns were focused on the outcomes of curative resection rate and technical feasibility. However, as large experience accumulates, ESD is currently being applied to a wide variety of indications, with sufficient curability. Therefore, the issue of local recurrence or metachronous lesions is receiving more attention recently. Moreover, the healing process of post-ER ulcers is still not completely understood.
In general, after a successful curative ER, follow-up endoscopy is expected to demonstrate a homogeneous and flat epithelized scar covered by normal mucosa with some grade of fibrosis [
Irregular erythema and irregular erythema with nodular scar change were significantly more frequently noted in the male group in multivariate analysis. In another study, gastric ulcer or gastric ulcer perforation was predominant in male patients [
Nodular scar change after ER was significantly related to smoking in multivariate analysis. A number of studies have provided evidence that smoking is a major cause of gastrointestinal disorders, including chronic inflammation such as peptic ulcer and inflammatory bowel disease and cancer of the gastrointestinal tract [
Mucosal defect was related to the histopathology (cancer) and location of the lesion (angle and antrum) in multivariate analysis. Tumor location might be as influential in the healing process for ER-induced ulcers [
The irregular erythema with nodularity and mucosal defect scar pattern was significantly related to liver disease and chronic kidney disease. Although the pathophysiology of this phenomenon is incompletely understood, the incidence of, frequency of bleeding from, and severity of bleeding from peptic ulcer disease are all increased in patients with liver disease [
This study has some limitations. First, there may have been a potential selection or information bias resulting from the retrospective nature of the study. Second, our study had a relatively small number of patients. Therefore, a further large-scale prospective study involving a greater number of patients is warranted.
In conclusion, this study revealed the clinicopathologic factors related to atypical post-ESD scars, especially suspicious for local recurrence. Although local recurrence is rare after ESD, screening for local recurrence is important. However, the risk of bleeding may increase if excessive biopsy is performed in patients with a bleeding tendency (patients with chronic kidney disease or liver disease, those taking antiplatelets or anticoagulation agents, etc.). Therefore, understanding the factors associated with atypical post-ESD scar morphology may reduce the bleeding risk from unnecessary biopsy.
No potential conflict of interest relevant to this article was reported.
Endoscopic classification relating to the endoscopic resection scar. (A) Irregular erythema. (B) Nodularity. (C) Mucosal defect.
Clinical outcomes of 274 gastric tumors treated by endoscopic submucosal dissection. ESD, endoscopic submucosal dissection; APC, argon plasma coagulation.
Baseline Clinicopathologic Characteristics of 274 Lesions in 264 Patients
Value | |
---|---|
Age (years) | 64.4±9.3 |
Sex | |
Male | 175 (66.3) |
Female | 89 (33.7) |
Underlying diseases | |
Hypertension | 106 (40.2) |
Diabetes mellitus | 46 (17.4) |
Chronic kidney disease | 11 (4.2) |
Liver cirrhosis | 5 (1.9) |
Cardiovascular disease | 19 (7.2) |
Smoking | 83 (31.4) |
Alcohol drinking | 124 (47.0) |
History of peptic ulcer | 3 (1.1) |
Medication | |
Aspirin | 37 (14.0) |
Antiplatelet agent | 15 (5.7) |
NSAIDs | 7 (2.7) |
Anticoagulant | 1 (0.4) |
Steroid | 1 (0.4) |
Location | |
Antrum/angle | 248 (90.5) |
Body/fundus/cardia | 26 (9.5) |
Macroscopic type | |
Superficial elevated | 246 (89.8) |
Flat or superficial depressed | 28 (10.2) |
Lesion size | |
<2 cm | 208 (75.9) |
≥2 cm | 66 (24.1) |
82 (29.9) | |
Histopathology | |
Adenoma | 201 (73.4) |
Mucoal cancer | 70 (25.5) |
Submucosal cancer | 3 (1.1) |
Values are presented as mean±standard deviation or number (%).
NSAID, non-steroidal anti-inflammatory drug.
Therapeutic Outcomes from Endoscopic Submucosal Dissection of 274 Lesions
Value | |
---|---|
Procedure time (minutes) | 56.3±35.0 |
Yes | 271 (98.9) |
No | 3 (1.1) |
Complete resection | |
Yes | 266 (97.0) |
No | 8 (3.0) |
Curative resection | |
Yes | 266 (97.0) |
No | 8 (3.0) |
Adverse events | |
Significant bleeding | 0 (0.0) |
Perforation | 3 (1.1) |
Delayed bleeding | 1 (0.4) |
Scar pattern | |
Irregular erythema | 101 |
Nodularity | 85 |
Mucosal defect | 104 |
Follow-up duration (months) | 24.6±19.3 |
Recurrence | 4 (1.5) |
Values are presented as mean±standard deviation or number (%).
Clinicopathologic Characteristics of Patients with Tumor Recurrence
Patient No. | Age (years) | Sex | Diagnosis | Comorbidity | Smoking | Tumor location | Specimen size (mm) | Curative resection | Follow-up duration (months) | Irregular erythema | Nodularity | Mucosal defect | Additional treatment |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 64 | F | LGA | HT, DM | No | Antrum | 26 | Yes | 76 | No | Yes | No | Surgery |
2 | 78 | M | Cancer | DM, CKD | Yes | Antrum | 26 | Yes | 17 | Yes | Yes | Yes | Observation |
3 | 66 | M | LGA | No | No | Antrum | 25 | Yes | 35 | Yes | No | No | APC |
4 | 70 | M | LGA | LC | Yes | Cardia | 31 | Yes | 19 | Yes | No | Yes | Surgery |
LGA, low-grade adenoma; HT, hypertension; DM, diabetes mellitus; CKD, chronic kidney disease; APC, Argon plasma coagulation; LC, liver cirrhosis.
Univariate Analysis of Scar Patterns for Predicting Tumor Recurrence
Irregular erythema |
Nodularity |
Mucosal defect |
Irregular erythema+nodularity |
Irregular erythema+nodularity+mucosal defect |
|||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | ||||||
Male | 2.30 | 1.32~4.02 | 0.003 | 2.24 | 1.24~4.03 | 0.007 | 0.95 | 0.57~1.60 | 0.854 | 3.92 | 1.48~10.42 | 0.003 | 6.54 | 0.84~50.00 | 0.067 |
Age ≥65 years | 0.81 | 0.49~1.32 | 0.392 | 0.60 | 0.36~1.00 | 0.050 | 1.37 | 0.83~2.24 | 0.217 | 0.67 | 0.34~1.34 | 0.257 | 0.67 | 0.22~2.03 | 0.471 |
Alcohol drinking | 1.45 | 0.89~2.38 | 0.136 | 1.64 | 0.98~2.75 | 0.058 | 0.63 | 0.38~1.03 | 0.063 | 1.57 | 0.79~3.12 | 0.198 | 1.41 | 0.46~4.32 | 0.542 |
Smoking | 1.46 | 0.87~2.47 | 0.153 | 3.22 | 1.87~5.54 | <0.001 | 0.52 | 0.30~0.91 | 0.020 | 2.22 | 1.11~4.46 | 0.022 | 0.97 | 0.29~3.24 | 1.000 |
HT | 1.25 | 0.76~2.06 | 0.378 | 0.92 | 0.55~1.56 | 0.765 | 1.02 | 0.62~1.67 | 0.950 | 1.41 | 0.71~2.80 | 0.328 | 1.29 | 0.42~3.96 | 0.651 |
DM | 1.28 | 0.68~2.41 | 0.447 | 1.01 | 0.52~1.98 | 0.970 | 0.98 | 0.51~1.86 | 0.943 | 1.31 | 0.56~3.06 | 0.537 | 1.44 | 0.38~5.44 | 0.706 |
Liver disease | 1.15 | 0.19~6.97 | 1.000 | 9.28 | 1.02~84.35 | 0.033 | 1.09 | 0.18~6.64 | 1.000 | 4.32 | 0.70~26.72 | 0.143 | 15.64 | 2.37~103.32 | 0.019 |
CVD | 1.44 | 0.58~3.61 | 0.433 | 1.22 | 0.47~3.16 | 0.690 | 0.68 | 0.25~1.83 | 0.446 | 1.62 | 0.51~5.13 | 0.497 | 2.46 | 0.51~11.93 | 0.243 |
CKD | 1.45 | 0.43~4.88 | 0.541 | 1.28 | 0.37~4.51 | 0.743 | 2.02 | 0.60~6.80 | 0.247 | 2.44 | 0.62~9.65 | 0.184 | 5.09 | 0.98~26.42 | 0.032 |
History of PUD | 0.34 | 0.04~2.92 | 0.419 | 0.44 | 0.05~3.81 | 0.669 | 0.61 | 0.56~0.67 | 0.086 | 0.34 | 0.04~2.92 | 0.419 | 0.95 | 0.93~0.98 | 1.000 |
Hazard drug | 1.14 | 0.62~2.08 | 0.673 | 0.86 | 0.45~1.65 | 0.657 | 0.98 | 0.53~1.79 | 0.937 | 1.25 | 0.55~2.81 | 0.593 | 1.18 | 0.31~4.43 | 0.733 |
HP infection | 0.78 | 0.45~1.35 | 0.378 | 1.23 | 0.71~2.13 | 0.465 | 1.53 | 0.91~2.60 | 0.110 | 0.81 | 0.38~1.76 | 0.600 | 1.49 | 0.47~4.71 | 0.539 |
Location (infra-angle) | 0.65 | 0.29~1.47 | 0.302 | 0.70 | 0.30~1.60 | 0.389 | 8.40 | 1.94~35.71 | <0.001 | 0.39 | 0.15~1.00 | 0.043 | 1.06 | 1.03~1.09 | 0.620 |
Metaplasia | 0.83 | 0.50~1.38 | 0.472 | 1.03 | 0.60~1.74 | 0.928 | 0.96 | 0.58~1.59 | 0.864 | 1.14 | 0.56~2.35 | 0.715 | 0.93 | 0.30~2.93 | 1.000 |
Cancer | 1.38 | 0.80~2.39 | 0.247 | 0.86 | 0.48~1.56 | 0.627 | 3.04 | 1.75~5.28 | <0.001 | 1.14 | 0.54~2.44 | 0.729 | 1.77 | 0.56~5.61 | 0.341 |
Tumor morphology (flat or depressed) | 0.95 | 0.42~2.14 | 0.894 | 1.06 | 0.46~2.45 | 0.892 | 0.75 | 0.33~1.73 | 0.503 | 1.40 | 0.50~3.95 | 0.562 | 2.83 | 0.73~10.97 | 0.136 |
Lesion size ≥20 mm | 1.48 | 0.84~2.60 | 0.171 | 1.05 | 0.58~1.91 | 0.872 | 1.64 | 0.94~2.87 | 0.083 | 1.80 | 0.86~3.75 | 0.116 | 0.56 | 1.12~2.59 | 0.740 |
Specimen size ≥40 mm | 1.63 | 0.91~2.90 | 0.097 | 0.74 | 0.39~1.41 | 0.359 | 1.98 | 1.11~3.53 | 0.019 | 0.92 | 0.40~2.13 | 0.847 | 0.28 | 0.04~2.19 | 0.309 |
Hemostasis at SLE | 1.18 | 0.65~2.17 | 0.589 | 1.22 | 0.65~2.29 | 0.527 | 1.48 | 0.81~2.69 | 0.200 | 1.52 | 0.69~3.35 | 0.301 | 2.64 | 0.83~8.41 | 0.090 |
Procedural duration ≥1 hour | 1.51 | 0.91~2.50 | 0.110 | 1.66 | 0.98~2.80 | 0.058 | 0.88 | 0.53~1.46 | 0.613 | 2.17 | 1.09~4.33 | 0.026 | 2.11 | 0.69~6.46 | 0.183 |
OR, odds ratio; CI, confidence interval; HT, hypertension; DM, diabetes mellitus; CVD, cardiovascular disease; CKD, chronic kidney disease; PUD, peptic ulcer disease; HP, Helicobacter pylori; SLE, second-look endoscopy.
Multivariate Analysis of Scar Patterns for Predicting Tumor Recurrence
Irregular erythema |
Nodularity |
Mucosal defect |
Irregular erythema+nodularity |
Irregular erythema+nodularity+mucosal defect |
|||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | ||||||
Male | 2.25 | 1.15~4.39 | 0.018 | 1.48 | 0.72~1.59 | 0.288 | 1.63 | 0.82~3.25 | 0.164 | 3.46 | 1.13~10.64 | 0.030 | 5.18 | 0.64~41.67 | 0.124 |
Age ≥65 years | 0.83 | 0.49~1.40 | 0.480 | 0.76 | 0.43~1.34 | 0.342 | 1.26 | 0.72~2.22 | 0.424 | 0.62 | 0.28~1.38 | 0.245 | 0.71 | 0.19~2.64 | 0.604 |
Alcohol drinking | 1.03 | 0.56~1.90 | 0.924 | 0.89 | 0.46~1.71 | 0.719 | 0.71 | 0.36~1.41 | 0.333 | 0.95 | 0.41~2.19 | 0.896 | |||
Smoking | 0.99 | 0.53~1.87 | 0.983 | 2.51 | 1.30~4.85 | 0.006 | 0.50 | 0.25~1.01 | 0.054 | 1.21 | 0.52~2.80 | 0.665 | |||
Liver disease | 7.17 | 0.73~70.10 | 0.090 | 4.80 | 0.68~33.71 | 0.115 | 16.99 | 1.72~167.88 | 0.015 | ||||||
History of PUD | 0.00 | 0.00 | 0.999 | ||||||||||||
CKD | 3.91 | 0.86~17.77 | 0.078 | 12.71 | 1.79~90.27 | 0.011 | |||||||||
HP infection | 1.66 | 0.93~2.96 | 0.088 | ||||||||||||
Location (infra-angle) | 8.20 | 1.74~38.46 | 0.008 | 0.39 | 0.14~1.10 | 0.075 | 0.138 | ||||||||
Cancer | 2.81 | 1.54~5.14 | 0.001 | ||||||||||||
Tumor morphology (flat or depressed) | 1.60 | 0.32~8.54 | 0.564 | ||||||||||||
Lesion size ≥20 mm | 1.29 | 0.66~2.51 | 0.454 | 1.63 | 0.82~3.25 | 0.165 | 1.66 | 0.71~3.88 | 0.246 | ||||||
Specimen size ≥40 mm | 1.34 | 0.69~2.60 | 0.394 | 1.05 | 0.52~2.13 | 0.886 | |||||||||
Hemostasis at SLE | 3.13 | 0.81~12.06 | 0.098 | ||||||||||||
Procedural duration ≥1 hour | 1.32 | 0.75~2.33 | 0.333 | 1.56 | 0.89~2.72 | 0.118 | 1.93 | 0.87~4.28 | 0.106 | 2.42 | 0.69~8.54 | 0.168 |
OR, odds ratio; CI, confidence interval; PUD, peptic ulcer disease; CKD, chronic kidney disease; HP, Helicobacter pylori; SLE, second-look endoscopy.