Transcript 病理科 實證期刊閱讀報告 EBM-style Journal Reading 報告人： 蘇子誠 Email:[email protected] 指導臨床教師：朱斾億醫師 日期：2009/4/20 地點：病理科會議室 Clinical Scenario （臨床情境）  Lymphatic invasion is known as an independent predictor of lymph node metastasis in gastric cancer.

病理科
實證期刊閱讀報告
EBM-style Journal Reading
報告人： 蘇子誠
Email:[email protected]
指導臨床教師：朱斾億醫師
日期：2009/4/20
地點：病理科會議室
Clinical Scenario （臨床情境）
 Lymphatic invasion is known as an independent predictor of
lymph node metastasis in gastric cancer. However, the
diagnosis of lymphatic invasion is sometimes difficult by
hematoxylin-eosin (H&E) staining because complete
obliteration of the lymphatic lumen by cancer cells is not
diagnosed as lymphatic invasion. Furthermore, retraction
artifacts due to tissue shrinkage during fixation are
sometimes confused as the true tumor emboli in lymphatic
vessels.
 More recently, a new monoclonal antibody, designated as
D2-40, became available to identify the tumor emboli in the
lymphatic vessels in paraffin sections and was proved to be
a specific marker for the lymphatic vessels
 Whether increase identified rate of lymphatic permeation
with IHC stain of D2-40 compared with H&E stain?
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Clinical Uncertainty → PICO 問題
 Does patient with gastric carcinoma increase
sensitivity for identification of lymphatic
permeation with immunohistochemical stain of
D2-40 compared with conventional H&E stain?
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臨床個案的PICO
Patient / Problem
Patient with gastric
carcinoma
Intervention
D2-40 IHC staining
Comparison
H&E staining
Outcome
sensitivity for identification
of lymphatic permeation
Type of Question: Diagnosis
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Search Terms & Strategy:
（搜尋關鍵字與策略）
 資料庫：PubMed
 搜尋日期： 2009/4/10
 搜尋關鍵字與隅策略：(("stomach"[MeSH
Terms] OR "stomach"[All Fields] OR
"gastric"[All Fields]) AND
("carcinoma"[MeSH Terms] OR
"carcinoma"[All Fields])) AND #1

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Best available evidence:
（挑選可獲得之最佳研究證據）
 Citation/s: Evaluation of lymphatic
invasion in primary gastric cancer
 by a new monoclonal antibody, D2-40
 Lead author's name : Yutaka Yonemura
MD, PhDa,*, Yoshio Endou PhD
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The Study: （研究效度）- 1
 Seventy-eight patients with primary gastric cancer. All
patients underwent gastrectomy with lymph node
dissection.
 All surgical specimens of the primary tumors and
regional lymph nodes were examined histologically by
routine hematoxylin-eosin (H&E) staining.
 All statistical calculations were performed using the
SPSS statistical software (SPSS, Inc, Chicago, Ill).
The v2 test was used to determine the significance of
intergroup differences.
 Level of Evidence: 3b
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The Study: （研究效度）- 2
本篇文獻的PICO (T)
Patient /
Problem
Patient of gastric adenocarcinoma
Lymphatic permeation identified by H&E
Intervention
staining
Lymphatic permeation identified by IHC
Comparison
staining of D2-40
Outcome
Sensitivity for lymph node metastasis
by the lymphatic invasion
Sensitivity for the prediction of lymph
node metastasis from the lymphatic
invasion status
Time
x
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The Evidence: （研究重要結果）- 1



Specimens examined by H&E staining showed a
false-negative rate of lymphatic invasion in 21.8%
(17/78) and a false-positive rate in 5.1% (4/78).
Positive rate of lymphatic invasion by H&E staining
was 27% (21/78), and that by D2-40 was 44% (34/78)
( P<.001).
Sensitivity for lymph node metastasis by the
lymphatic invasion diagnosed by D2-40 was
significantly higher (89%, 24/27) than by H&E
staining (41%, 11/27).
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The Evidence: （研究重要結果）- 2
D2-40 D2-40
Lym(-) Lym(+) total
H&E
H&E
Lym(-) 40
Lym(+) 4
total
44
17
17
34
57
21
78
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The Evidence: （研究重要結果）- 3
D2-40
LN meta
Ly+
Ly-
N+
24
3
27
Sensitivity, 89% (24/27)
N0
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38
51
Specificity, 78% (38/51)
37
44
78
Accuracy, 79% (62/78)
H&E
LN meta
Ly+
Ly-
N+
15
12
27
Sensitivity, 55% (15/27)
N0
6
45
51
Specificity, 88% (45/51)
21
57
78
Accuracy, 77% (60/78)
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Comment & Discussion: -1

VEGFR-3 and LYVE-1 are also specific markers for
lymphatic endothelial cells, but the available antibodies
against VEGFR-3 or LYVE-1 do not react with the
paraffinembedded tissues.

As reported by Kahn et al, D2-40 is a new selective marker
of lymphatic endothelial cells and does not react with
endothelial cells of blood vessels. Furthermore,
immunoreactivity by D2-40 antibody was clearly detected
on all sections from formalin-fixed and paraffin-embedded
blocks.

By using D2-40 immunostaining, false-positive rate for
lymphatic invasion by H&E staining was 5% (4/78), and
the retraction artifact around the cancer nests may be
initially spuriously diagnosed as lymphatic invasion.
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Comment & Discussion: -2

In contrast, a tumor embolus that obliterated the lymphatic
lumen could be clearly diagnosed by D2-40 immunoreactivity,
and 17 tumors, which had been diagnosed as no lymphatic
invasion by H&E staining, were correctly diagnosed as
having lymphatic invasion after D2-40 staining.

In contrast, only 17 (50%) of 34 lymphatic invasions,
confirmed by D2-40 staining, were correctly diagnosed by
H&E staining.

Lymph node metastasis was significantly related with the
tissue status of lymphatic invasion, which were diagnosed by
D2-40 immunohistochemistry. Sensitivity of lymph node
metastasis predicted by the lymphatic invasion status in D240 staining was 89% and was higher (41%) than that in H&E
staining. These results indicate that the findings of lymphatic
invasion by D2-40 are more reliable to predict lymph node
metastasis than by H&E staining.
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回到臨床個案情境
Clinical bottom line 臨床決策底線
 The diagnosis of lymphatic invasion by D2-40 is more
sensitive than H&E staining. Sensitivity for the
prediction of lymph node metastasis from the lymphatic
invasion status in primary tumor by D2-40 was
significantly higher than by H&E staining.
 證據等級3b, 建議等級B
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結 論 （標題 Title）
The use of D2-40 immunoreactions for the
routine evaluation of lymphatic invasion
in gastric cancer is recommended
Update By:
April. 20, 2009
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