Accuracy of diagnostic demarcation of undifferentiated-type early gastric cancers for magnifying endoscopy with narrow-band imaging: endoscopic submucosal dissection cases
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Abstract
Background
The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) for undifferentiated-type early gastric cancers (UD-type EGCs) is unclear. The present study examined the accuracy of the diagnostic demarcation of lesions using ME-NBI.
Methods
The study population consisted of 76 patients with UD-type EGC lesions measuring ≤20 mm in diameter using white-light imaging (WLI) and endoscopic ultrasonography and diagnosed as intramucosa and UL(−); all the lesions were confirmed as early gastric cancer based on postoperative pathological examination. All the patients had undergone an initial endoscopic submucosal dissection (ESD) at this hospital between January 2010 and January 2014. After marking with demarcation lines at the utmost oral and anal sites of the lesion using argon plasma coagulation under ME-NBI for intervention, the cases with demarcations that were consistent with the postoperative pathological findings were defined as having been accurately diagnosed. The inflammatory cell infiltration (Updated Sydney System, USS) were also assessed.
Results
The diagnostic demarcations of the lesion were consistent in 62 cases (81.6 %). The accurate diagnosis rate was higher for the USS cases with mild neutrophil and monocyte infiltration (P < 0.05). The addition of ME-NBI to WLI improved the accurate diagnosis rate by 27.6 %.
Conclusion
The use of ME-NBI in diagnostic demarcation of UD-type EGCs is recommended.
Keywords
Undifferentiated-type cancer Gastric cancer Endoscopic resection Magnifying endoscopyIntroduction
With the extension of indications for endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancers (UD-type EGCs) [1, 2, 3], an improvement in preoperative diagnostic performance is currently being sought. According to the reports of Gotoda et al. [2] and Hirasawa et al. [3], UD-type EGC is classified under the extended indications for ESD in the Japanese Gastric Cancer Association Guideline [1] insofar as it is an intramucosal carcinoma measuring ≤20 mm in diameter, ulcer scar free, and without invasion into the lymphatic and blood vessels, thereby having a negligible risk of lymph node metastasis. The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) in delineating the demarcation of differentiated-type early gastric cancer has been reported [4, 5, 6], whereas in UD-type EGCs, the diagnostic delineation of lesion demarcation is difficult because of the presence of proliferative zone extension [7], and the usefulness of ME-NBI is thus unclear for these lesions. There have been reports on ME-NBI findings for UD-type EGCs, and Nakayoshi et al. [8] reported that corkscrew patterns were demonstrated in approximately 90 % of cases. Okada and colleagues investigated the by-growth pattern ME-NBI features of undifferentiated-type carcinomas and documented their post-ESD histopathological findings, indicating a significant expansion of intervening parts (inter-crypt regions) in neoplastic lesions, compared with noncancerous regions [9]. However, whether such expansion of intervening parts might be useful for the diagnostic demarcation of lesions has not been sufficiently explored, and the extent to which ME-NBI might yield an additional effect, compared with routine observation using white-light imaging (WLI), in terms of the diagnostic demarcation of lesions, remains uncertain. This study was conducted to clarify the accuracy of the diagnostic demarcation of lesions using ME-NBI in UD-type EGCs and to assess its additional effect.
Patients and methods
This study is a prospective interventional study. The intervention is marking with demarcation lines at the utmost oral and utmost anal sites of the lesion by argon plasma coagulation (APC) under ME-NBI.
Findings for an expanded intervening part. The inter-crypt region (intervening part) between the ducts is expanded in the cancerous portion compared with the noncancerous portion
Undifferentiated-type early gastric cancer invasion collated with magnifying endoscopy (ME)–narrow-band imaging (NBI) findings. a A carcinoma confined to the proliferative zone is shown to have an expanded intervening part using ME-NBI. b A carcinoma extending from the superficial layer into the proliferative zone is visualized as exhibiting weave-like microvessels using ME-NBI. c A carcinoma involving the whole layer of the mucosa is visualized as having a corkscrew pattern using ME-NBI
Actual argon plasma coagulation (APC) markings. The dotted line indicates a tumor border region as viewed under white-light imaging (WLI). The arrow points to a tumor border region as viewed using magnifying endoscopy with NBI (ME-NBI). a Tumor border at the utmost rostral site under WL. b Demarcation line as viewed using ME-NBI (coinciding with a). c A higher-magnification view of b. d An APC marking placed on the demarcation line. e Tumor border at the utmost anal site under WL. f Demarcation line as viewed using ME-NBI (inconsistent with e). g A higher-magnification view of f. h An APC marking placed on the demarcation line
Postendoscopic submucosal dissection (ESD) histopathological specimen from patient in Fig. 3. The APC marking coincided with the cancerous–noncancerous border on the histopathological slide
Furthermore, the accurate diagnosis rate using ME-NBI was also calculated and was regarded as an additional effect to the accurate diagnosis rate obtained using WLI alone.
In endoscopic therapy for UD-type EGCs, patients were provided with an explanation of the merits and demerits of ESD and gave their informed consent before the operation. An in-hospital consensus has been secured as to the extended therapeutic indications of ESD for UD-type EGCs. This study was approved by the Institutional Review Board of Cancer Institutional Hospital (IRB No. 2014-1048).
Statistical analysis
A comparison between the two groups was performed using the Fisher exact test. The mean and standard deviation of the tumor diameter and the proliferative zone extension distance were calculated and evaluated using the t test and the F test; if the resulting data failed to show a homogeneity of variance, these were evaluated using the Mann–Whitney U test. Any differences were considered to be statistically significant when P < 0.05. The statistical analysis was performed using StatView software, Version 5.0 (SAS Institute, Cary, NC, USA).
Results
Comparison of accurately diagnosed cases and misdiagnosed cases
n = 76 | Accurately diagnosed | Misdiagnosed | P value | |
---|---|---|---|---|
Number of cases (%) | 62 (81.6) | 14 (18.4) | ||
Age | 54.5 ± 11.3 | 58.5 ± 10.0 | NS | |
Male, n (%) | 36 (58.1) | 9 (64.3) | NS | |
Tumor-occupied site, n (%) | ||||
U region | 4 (6.5) | 2 (14.3) | ||
M region | 24 (38.7) | 8 (57.1) | ||
L region | 34 (54.8) | 4 (28.6) | ||
Depth of tumor invasion, n (%) | 0.054 | |||
Intramucosal | 57 (91.9) | 10 (71.4) | ||
Submucosal (SM) | 5 (8.1) | 4 (28.6) | ||
SM-slight (<500 μm) | 4 | 2 | ||
SM-massive (≥500 μm) | 1 | 2 | ||
Complication, n (%) | ||||
Hemorrhage | 2 (3.2) | 0 | ||
Perforation | 0 | 0 | ||
Curability, n (%) | <0.005 | |||
Complete (R0) resection | 53 (85.5) | 6 (42.9) | ||
Incomplete resection (horizontal margin positive) | 9 (14.5) | 8 (57.1) | ||
Mean diameter of tumor (mm) | 9.95 ± 6.36 | 19.07 ± 2.75 | <0.001 | |
Mean inter-crypt distance ratio (cancerous region/noncancerous region) | 1.91 | 1.22 | <0.05 | |
Proliferative zone extension distance (μm) | 302.4 ± 455.8 | 548.5 ± 564.0 | NS |
Accurate demarcation diagnosis rate according to degree of background mucosal status based on the Updated Sydney System
n = 76 | Normal to mild (%) | Moderate to marked (%) | P value |
---|---|---|---|
Atrophy | 87.2 (34/39) | 76.7 (28/37) | NS |
Intestinal metaplasia | 85.5 (53/62) | 64.3 (9/14) | NS |
Neutrophils | 87.1 (54/62) | 57.1 (8/14) | <0.05 |
Mononuclear cells | 93.5 (29/31) | 73.3 (33/45) | <0.05 |
Additional effect of ME-NBI. Diagnosis with white-light imaging (WLI) was feasible in 41 cases (53.9 %), whereas it was difficult or not feasible for 35 lesions (46.1 %). With magnifying endoscopy combined with NBI (ME-NBI), the diagnosis became feasible for 21 (27.6 %) of these lesions, and the accurate diagnosis rate increased to 81.5 % because of this additive effect
Discussion
The diagnostic demarcation of lesions can be difficult in patients with UD-type EGCs because the proliferative zone extension does not resemble that observed in differentiated-type early gastric cancers [7]. According to reports describing ESD for UD-type EGCs, in fact, the surgical margin-positive rate ranged from 1.7 % to 52.6 % and the curative resection rate ranged from 63.9 % to 82.5 %; hence, both these parameters suggest noticeable inter-institutional differences [11, 12, 13, 14, 15, 16, 17, 18]. The curative resection rate has been reported to be 91.1 % for differentiated-type early gastric cancers [19], which seems to be higher than that for UD-type EGCs. A simple comparison of the curative resection rate cannot be performed using the present data because some noncurative resections that were performed because of the size/depth of the tumor and/or the presence of vascular invasion were included; in the afore-described previously reported ESD cases of UD-type EGCs, the surgical margin-positive rate was lower even if the DL was not accurately diagnosed because a perilesional biopsy had been performed or because ESD had been performed by securing a margin ≥10 mm around the lesion [11, 12, 13, 14, 15, 16, 17, 18]. Hence, the diagnostic demarcation was accurate among the cases that were regarded as complete resection cases. Nevertheless, the present investigation involved stricter conditions for accurate diagnosis in that DL markings by APC and errors within a 1-mm margin were defined as requirements for accurate diagnosis and were used in the present series. Although a detailed report concerning the accuracy of the diagnostic demarcation of UD-type EGCs has not yet been published, the present results demonstrate that an accurate diagnosis rate of 81.6 % might be achievable using ME-NBI. The accurate diagnostic demarcation rate attained using ME-NBI was considered to be appreciably high, considering that the accurate diagnostic demarcation rate using WLI was 53.9 % and that the aforementioned surgical margin-positive rate was achieved using ESD for UD-type EGCs. Therefore, the present data suggest that the diagnostic capability for UD-type EGCs may be enhanced using the ME-NBI technique, and the use of ME-NBI for the diagnostic delineation of UD-type EGCs lesions before ESD is recommended. Complete resection cases and cases with lesions ≤10 mm were more frequent, the mean inter-crypt distance was longer, and the background mucosal inflammation was milder among the accurately diagnosed cases compared with the misdiagnosed cases. Cell growth potential is reportedly enhanced as a reaction in terms of inflammatory cell infiltration [20, 21, 22], and this would imply pronounced cellular mitotic activities via DNA synthesis. In other words, the more pronounced the inflammatory cell infiltration, the greater the likelihood of tumor growth, suggesting that the extension range eventually becomes widened, resulting in an increased tumor diameter. Therefore, it can be inferred that the tumor diameter was significantly smaller in the accurately diagnosed cases inasmuch as the inflammation was milder in those cases. This point was probably reflected in the finding that complete resection cases were significantly more frequent among the cases with milder inflammation. The milder inflammation of the surrounding mucosa implied a relative scarcity of mononuclear cells and neutrophils intruding into the intervening parts, enabling the inter-crypt distance of the surrounding non-carcinomatous mucosa to be retained and causing a distinction from the carcinomatous intervening parts that were extended as a result of the malignant cell intrusion. Consequently, the DL was readily recognizable using ME-NBI. As a matter of fact, the present results suggested that the accurate diagnosis rate increased progressively with an increasing disparity in the inter-crypt distance between the cancerous region and the noncancerous region, because the cancerous/noncancerous region ratio of the inter-crypt distance was about 1.22 times in the misdiagnosed cases compared with about 1.91 times in the accurately diagnosed cases. It follows that it would be difficult to delineate diagnostic demarcation, even using ME-NBI, in cases with a narrower inter-crypt distance in the cancerous region because of the scarcity of cancer cells as well as in cases with pronounced inflammatory cell infiltration, resulting in diagnostic limitations in a little less than 20 % of cases. This finding stresses the need for pretreatment biopsies in surrounding regions, as stated in the Guidelines of the Japanese Gastric Cancer Association [1].
This study has some other limitations. In this study, the ME-NBI diagnosis was performed onsite, but the WLI diagnosis was made by reviewing still images. As stated in the Patients and Methods, this difference was thought to have a minimal influence, because the diagnosis was thought to be correct insofar as the WLI-diagnosed extent coincided with the position of the ME-NBI-based APC-marked region. The present investigation was a single-center study. The lesions were demarcated using APC on the utmost oral and utmost anal sides in this study, but lesion demarcation may be difficult at some other sites or may be more readily accomplished elsewhere.
Although this study was performed at a single center, the results were considered to be notable because our medical institution is a high-volume center where ESD for gastric cancer is performed on more than 300 patients annually, and the subjects included in the present series had been accumulated over 4 years; therefore, these cases were considered to be suitable for an evaluation of relatively uncommon UD-type EGC cases. As well, the present study was considered to be significant because the predetermined placement of markings at the utmost oral and utmost anal sites of the lesion delineation enabled the preclusion of the selective sampling of regions that were readily accessible or difficult to access when demarcating the lesion.
In conclusion, the acceptable error was set at 1 mm because the aim of this study was to clarify the diagnostic accuracy of ME-NBI. If ME-NBI could be shown to have a high diagnostic accuracy, it would enable a more precise determination of the size of a lesion and would prove useful for determining whether ESD is indicated in a particular case. The diagnostic capability for UD-type EGCs may be enhanced using the ME-NBI, and the use of ME-NBI for the diagnostic delineation of UD-type EGCs lesions before to ESD is recommended.
Notes
Conflict of interest
There is no conflict of interest in this study.
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