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Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE
Yong Chan Lee |
Professor of Medicine Director, Gastrointestinal Research Laboratory Veterans Affairs Medical Center, Univ. California San Francisco San Francisco, USA |
Jong Pil Im | Seoul National University College of Medicine, Seoul, Korea |
Robert S. Bresalier | University of Texas M. D. Anderson Cancer Center, Houston, USA |
Steven H. Itzkowitz | Mount Sinai Medical Center, NY, USA |
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Yuji Maehata1, Shotaro Nakamura2, Motohiro Esaki1, Fumie Ikeda1, Tomohiko Moriyama1, Risa Hida3, Ema Washio1, Junji Umeno1, Minako Hirahashi3, Takanari Kitazono1, Takayuki Matsumoto2
Correspondence to: Yuji Maehata, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan, Tel: +81-92-642-5261, Fax: +81-92-642-5273, E-mail: ymaehata@intmed2.med.kyushu-u.ac.jp
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gut Liver 2017;11(5):628-634. https://doi.org/10.5009/gnl16357
Published online April 11, 2017, Published date September 15, 2017
Copyright © Gut and Liver.
Gastric cancers develop even after successful A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful In the Early gastric cancers after Background/Aims
Methods
Results
Conclusions
Keywords:
Gastric cancer is the fifth most common cancer and the third leading cause of cancer death in the world.1 It has been clarified that the development of gastric cancer is mostly caused by
In the present study, we have conducted a multicenter propensity score-matched study to clarify the characteristics of early gastric cancers discovered after
This was a multicenter, retrospective, and propensity score-matched study from Kyushu University Hospital and other 18 hospitals in Fukuoka, Yamaguchi, and Ehime, Japan. All these hospitals have participated the Kyushu University multicenter endoscopic submucosal dissection database (KYU-MED) study. This database was approved by the Institutional Review Board of Kyushu University Hospital and has been registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as number UMIN000009190. Written informed consent was obtained from each patient included in the study.
Between June 2003 and October 2014, a total of 2,153 patients with early gastric cancer who were treated by endoscopic submucosal dissection (ESD)12 at the participating hospitals were registered in KYU-MED study. Of these, 670 patients were not investigated for their
In this study, PGC was defined as a gastric carcinoma that developed in a patient who had no previous history of gastric cancer. MGC was defined as a new carcinoma that developed in other areas at least 1 year after the endoscopic resection of the initial gastric cancer. In patients with MGC, the initial early gastric cancer had been treated by ESD or endoscopic mucosal resection in another hospital. All endoscopic examinations and ESDs were performed by the specialized endoscopists who had a license for Board Certification of Japan Gastroenterological Endoscopy Society in 18 participated hospitals.
The histopathological assessment of the resected specimens was performed by the senior pathologist in each hospital. In 44 patients who had more than one carcinoma at the time of ESD, we evaluated only one carcinoma of which the depth of invasion and/or size was greater than the others. Among these 44 patients, we chose the carcinoma invading the submucosa in spite of the smaller size in three patients. Location, macroscopic type, and histological findings of gastric cancers were classified according to the Japanese classification and Paris classification of gastric carcinoma.14,15 Namely, the location was classified by dividing stomach into three equal sections: upper, middle, and lower. Macroscopic type was classified either as elevated (type 0–I, IIa, and IIa+IIc) or as depressed type (type 0–IIb, IIc, IIc+IIa, IIc+III, and III). Histopathologically, well and/or moderately differentiated adenocarcinomas were regarded as differentiated type, while poorly differentiated adenocarcinoma and/or signet-ring cell carcinoma were as undifferentiated type. Presence or absence of ulcerations with or without scars, submucosal invasion, lymphatic invasion and venous invasion were also assessed with the resected specimens. When massive invasion to the submucosa and/or lymphovascular invasion by carcinoma was observed, an additional gastrectomy with regional lymph node dissection was recommended to the patient.
Two of the authors (Y.M. and F.I.) performed all the statistical analyses. F.I. is an expert for the statistics. We used propensity score-matching analysis to adjust significant differences in the baseline clinical characteristics of patients and to reduce the influence of possible confounding factors. Propensity scores were calculated using a logistic regression model and variables included in the model were age, sex, and PGC/MGC (Fig. 1). After propensity scores were estimated, one-to-one nearest-neighbor matching without replacement was performed with a caliper of width equal to 0.2 of the standard deviation of the logit of the propensity score.13 Before and after propensity score-matching, we compared the clinicopathological characteristics of these enrolled patients between
In
After propensity score-matching, 67 patients with PGC and 29 patients with MGC were included in each group (p=1.000). Macroscopically, depressed type was more frequent in
As shown in Table 2, our multivariable logistic regression analysis determined that macroscopic depressed type (odds ratio, 3.80; 95% confidence interval, 2.00 to 7.49; p<0.0001) was the sole independent characteristics of early gastric cancer after
Table 3 compares the clinicopathological features between patients with PGC and those with MGC in
In the present study, we confirmed that gastric cancers including both PGCs and MGCs developed during a long-term period of up to 15 years (median, 4 years) after
To date, there have been reported several studies investigating the characteristics of gastric cancers discovered after
In the present study, MGC was more frequent in
It has been considered that
In
Our present study has several limitations. First, our study subjects were limited to patients with early gastric cancer treated by ESD, and patients with advanced gastric cancers or those obviously invading the submucosa were excluded. Thus, our results might not represent the characteristics of all the gastric cancers discovered after
In conclusion, our multicenter propensity score-matched study revealed that early gastric cancers after
This study was undertaken with the following hospitals in Fukuoka, Yamaguchi and Ehime Prefecture, Japan: Kyushu University Hospital, Kimura Hospital, Kyushu Central Hospital, Chihaya Hospital, Hamanomachi Hospital, Hakujyuji Hospital, Fukuoka Sanno Hospital, Fukuoka Red Cross Hospital, Onga Hospital, Kama Red Cross Hospital, Kyushu Hospital, Kokura Medical Center, Steel Memorial Yawata Hospital, Saiseikai Yahata General Hospital, Fukuoka Yutaka Central Hospital, Moji Ekisaikai Hospital, Shimonoseki City Hospital, Yamaguchi Red Cross Hospital, and Matsuyama Red Cross Hospital.
Comparison of Clinicopathological Characteristics between
Characteristic | All patients (n=1,053) | Propensity-matched patients (n=192) | ||||
---|---|---|---|---|---|---|
p-value | p-value | |||||
Sex | 0.075 | 0.855 | ||||
Male | 95 (81) | 691 (74) | 77 (80) | 78 (81) | ||
Female | 22 (19) | 245 (26) | 19 (20) | 18 (19) | ||
Age, yr | 71 (46–90) | 71 (30–96) | 0.397 | 72 (46–90) | 72 (47–92) | 0.886 |
Primary or metachronous cancers | <0.0001 | 1.000 | ||||
Primary gastric cancer | 67 (57) | 907 (97) | 67 (70) | 67 (70) | ||
Metachronous gastric cancer | 50 (43) | 29 (3) | 29 (30) | 29 (30) | ||
Location | 0.358 | 0.982 | ||||
Upper | 24 (21) | 148 (16) | 21 (22) | 22 (23) | ||
Middle | 45 (38) | 352 (38) | 36 (37) | 35 (36) | ||
Lower | 48 (41) | 436 (46) | 39 (41) | 39 (41) | ||
Macroscopic type | 0.001 | <0.0001 | ||||
Elevated type | 27 (23) | 354 (38) | 18 (19) | 45 (47) | ||
Depressed type | 90 (77) | 582 (62) | 78 (81) | 51 (53) | ||
Size (diameter), mm | 13 (2–75) | 14 (1–100) | 0.052 | 13 (2–75) | 14 (2–60) | 0.820 |
Histology | 0.473 | 0.721 | ||||
Differentiated type | 114 (97) | 892 (95) | 93 (97) | 91 (95) | ||
Undifferentiated type | 3 (3) | 44 (5) | 3 (3) | 5 (5) | ||
Depth of invasion | 0.190 | 0.051 | ||||
Mucosa | 97 (83) | 818 (87) | 79 (82) | 88 (92) | ||
Submucosa | 20 (17) | 118 (13) | 17 (18) | 8 (8) | ||
Ulceration or scar | 11 (9.4) | 66 (7.1) | 0.374 | 9 (9.4) | 7 (7.3) | 0.601 |
Lymphatic invasion | 7 (6.0) | 25 (2.7) | 0.076 | 6 (6.3) | 3 (3.1) | 0.497 |
Venous invasion | 2 (1.7) | 12 (1.3) | 0.663 | 1 (1) | 0 | 1.000 |
Adjunctive gastrectomy after ESD | 11 (9.4) | 66 (7.1) | 0.374 | 10 (10) | 5 (5.2) | 0.175 |
Results of a Multivariate Logistic Regression Analysis for the Characteristics of Early Gastric Cancers Discovered after
OR | 95% CI | p-value | |
---|---|---|---|
Macroscopic type | |||
Depressed type vs elevated type | 3.80 | 2.00–7.49 | <0.0001 |
Depth of invasion | |||
Submucosa vs mucosa | 1.85 | 0.65–5.69 | 0.252 |
Adjunctive gastrectomy after ESD | |||
Necessary vs unnecessary | 1.56 | 0.40–6.43 | 0.518 |
Comparison of the Clinicopathological Characteristics among All Patients with PGC and Those with MGC Discovered after
PGC (n=67) | MGC (n=50) | p-value | |
---|---|---|---|
Sex | 0.847 | ||
Male | 54 (81) | 41 (82) | |
Female | 13 (19) | 9 (18) | |
Age, yr | 69 (46–85) | 74 (56–90) | 0.003 |
Time after | 4.9 (1.0–15.0) | 3.8 (1.0–14.0) | 0.263 |
Time after latest negative endoscopy, yr | 1.9 (0.5–10.0) | 1.0 (0.5–2.0) | <0.0001 |
Location | 0.627 | ||
Upper | 15 (23) | 9 (18) | |
Middle | 27 (40) | 18 (36) | |
Lower | 25 (37) | 23 (46) | |
Macroscopic type | 0.049 | ||
Elevated type | 11 (16) | 16 (32) | |
Depressed type | 56 (84) | 34 (68) | |
Size (diameter), mm | 14 (3–75) | 11 (2–43) | 0.014 |
Histology | 1.000 | ||
Differentiated type | 65 (97) | 49 (98) | |
Undifferentiated type | 2 (3) | 1 (2) | |
Depth of invasion | 0.473 | ||
Mucosa | 57 (85) | 40 (80) | |
Submucosa | 10 (15) | 10 (20) | |
Ulceration or scar | 5 (7.5) | 6 (12) | 0.408 |
Lymphatic invasion | 2 (3) | 5 (10) | 0.136 |
Venous invasion | 0 | 2 (4) | 0.281 |
Adjunctive gastrectomy after ESD | 4 (6) | 7 (14) | 0.201 |
Gut and Liver 2017; 11(5): 628-634
Published online September 15, 2017 https://doi.org/10.5009/gnl16357
Copyright © Gut and Liver.
Yuji Maehata1, Shotaro Nakamura2, Motohiro Esaki1, Fumie Ikeda1, Tomohiko Moriyama1, Risa Hida3, Ema Washio1, Junji Umeno1, Minako Hirahashi3, Takanari Kitazono1, Takayuki Matsumoto2
1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan, 3Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Correspondence to: Yuji Maehata, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan, Tel: +81-92-642-5261, Fax: +81-92-642-5273, E-mail: ymaehata@intmed2.med.kyushu-u.ac.jp
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gastric cancers develop even after successful A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful In the Early gastric cancers after Background/Aims
Methods
Results
Conclusions
Keywords:
Gastric cancer is the fifth most common cancer and the third leading cause of cancer death in the world.1 It has been clarified that the development of gastric cancer is mostly caused by
In the present study, we have conducted a multicenter propensity score-matched study to clarify the characteristics of early gastric cancers discovered after
This was a multicenter, retrospective, and propensity score-matched study from Kyushu University Hospital and other 18 hospitals in Fukuoka, Yamaguchi, and Ehime, Japan. All these hospitals have participated the Kyushu University multicenter endoscopic submucosal dissection database (KYU-MED) study. This database was approved by the Institutional Review Board of Kyushu University Hospital and has been registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as number UMIN000009190. Written informed consent was obtained from each patient included in the study.
Between June 2003 and October 2014, a total of 2,153 patients with early gastric cancer who were treated by endoscopic submucosal dissection (ESD)12 at the participating hospitals were registered in KYU-MED study. Of these, 670 patients were not investigated for their
In this study, PGC was defined as a gastric carcinoma that developed in a patient who had no previous history of gastric cancer. MGC was defined as a new carcinoma that developed in other areas at least 1 year after the endoscopic resection of the initial gastric cancer. In patients with MGC, the initial early gastric cancer had been treated by ESD or endoscopic mucosal resection in another hospital. All endoscopic examinations and ESDs were performed by the specialized endoscopists who had a license for Board Certification of Japan Gastroenterological Endoscopy Society in 18 participated hospitals.
The histopathological assessment of the resected specimens was performed by the senior pathologist in each hospital. In 44 patients who had more than one carcinoma at the time of ESD, we evaluated only one carcinoma of which the depth of invasion and/or size was greater than the others. Among these 44 patients, we chose the carcinoma invading the submucosa in spite of the smaller size in three patients. Location, macroscopic type, and histological findings of gastric cancers were classified according to the Japanese classification and Paris classification of gastric carcinoma.14,15 Namely, the location was classified by dividing stomach into three equal sections: upper, middle, and lower. Macroscopic type was classified either as elevated (type 0–I, IIa, and IIa+IIc) or as depressed type (type 0–IIb, IIc, IIc+IIa, IIc+III, and III). Histopathologically, well and/or moderately differentiated adenocarcinomas were regarded as differentiated type, while poorly differentiated adenocarcinoma and/or signet-ring cell carcinoma were as undifferentiated type. Presence or absence of ulcerations with or without scars, submucosal invasion, lymphatic invasion and venous invasion were also assessed with the resected specimens. When massive invasion to the submucosa and/or lymphovascular invasion by carcinoma was observed, an additional gastrectomy with regional lymph node dissection was recommended to the patient.
Two of the authors (Y.M. and F.I.) performed all the statistical analyses. F.I. is an expert for the statistics. We used propensity score-matching analysis to adjust significant differences in the baseline clinical characteristics of patients and to reduce the influence of possible confounding factors. Propensity scores were calculated using a logistic regression model and variables included in the model were age, sex, and PGC/MGC (Fig. 1). After propensity scores were estimated, one-to-one nearest-neighbor matching without replacement was performed with a caliper of width equal to 0.2 of the standard deviation of the logit of the propensity score.13 Before and after propensity score-matching, we compared the clinicopathological characteristics of these enrolled patients between
In
After propensity score-matching, 67 patients with PGC and 29 patients with MGC were included in each group (p=1.000). Macroscopically, depressed type was more frequent in
As shown in Table 2, our multivariable logistic regression analysis determined that macroscopic depressed type (odds ratio, 3.80; 95% confidence interval, 2.00 to 7.49; p<0.0001) was the sole independent characteristics of early gastric cancer after
Table 3 compares the clinicopathological features between patients with PGC and those with MGC in
In the present study, we confirmed that gastric cancers including both PGCs and MGCs developed during a long-term period of up to 15 years (median, 4 years) after
To date, there have been reported several studies investigating the characteristics of gastric cancers discovered after
In the present study, MGC was more frequent in
It has been considered that
In
Our present study has several limitations. First, our study subjects were limited to patients with early gastric cancer treated by ESD, and patients with advanced gastric cancers or those obviously invading the submucosa were excluded. Thus, our results might not represent the characteristics of all the gastric cancers discovered after
In conclusion, our multicenter propensity score-matched study revealed that early gastric cancers after
This study was undertaken with the following hospitals in Fukuoka, Yamaguchi and Ehime Prefecture, Japan: Kyushu University Hospital, Kimura Hospital, Kyushu Central Hospital, Chihaya Hospital, Hamanomachi Hospital, Hakujyuji Hospital, Fukuoka Sanno Hospital, Fukuoka Red Cross Hospital, Onga Hospital, Kama Red Cross Hospital, Kyushu Hospital, Kokura Medical Center, Steel Memorial Yawata Hospital, Saiseikai Yahata General Hospital, Fukuoka Yutaka Central Hospital, Moji Ekisaikai Hospital, Shimonoseki City Hospital, Yamaguchi Red Cross Hospital, and Matsuyama Red Cross Hospital.
Table 1 Comparison of Clinicopathological Characteristics between
Characteristic | All patients (n=1,053) | Propensity-matched patients (n=192) | ||||
---|---|---|---|---|---|---|
p-value | p-value | |||||
Sex | 0.075 | 0.855 | ||||
Male | 95 (81) | 691 (74) | 77 (80) | 78 (81) | ||
Female | 22 (19) | 245 (26) | 19 (20) | 18 (19) | ||
Age, yr | 71 (46–90) | 71 (30–96) | 0.397 | 72 (46–90) | 72 (47–92) | 0.886 |
Primary or metachronous cancers | <0.0001 | 1.000 | ||||
Primary gastric cancer | 67 (57) | 907 (97) | 67 (70) | 67 (70) | ||
Metachronous gastric cancer | 50 (43) | 29 (3) | 29 (30) | 29 (30) | ||
Location | 0.358 | 0.982 | ||||
Upper | 24 (21) | 148 (16) | 21 (22) | 22 (23) | ||
Middle | 45 (38) | 352 (38) | 36 (37) | 35 (36) | ||
Lower | 48 (41) | 436 (46) | 39 (41) | 39 (41) | ||
Macroscopic type | 0.001 | <0.0001 | ||||
Elevated type | 27 (23) | 354 (38) | 18 (19) | 45 (47) | ||
Depressed type | 90 (77) | 582 (62) | 78 (81) | 51 (53) | ||
Size (diameter), mm | 13 (2–75) | 14 (1–100) | 0.052 | 13 (2–75) | 14 (2–60) | 0.820 |
Histology | 0.473 | 0.721 | ||||
Differentiated type | 114 (97) | 892 (95) | 93 (97) | 91 (95) | ||
Undifferentiated type | 3 (3) | 44 (5) | 3 (3) | 5 (5) | ||
Depth of invasion | 0.190 | 0.051 | ||||
Mucosa | 97 (83) | 818 (87) | 79 (82) | 88 (92) | ||
Submucosa | 20 (17) | 118 (13) | 17 (18) | 8 (8) | ||
Ulceration or scar | 11 (9.4) | 66 (7.1) | 0.374 | 9 (9.4) | 7 (7.3) | 0.601 |
Lymphatic invasion | 7 (6.0) | 25 (2.7) | 0.076 | 6 (6.3) | 3 (3.1) | 0.497 |
Venous invasion | 2 (1.7) | 12 (1.3) | 0.663 | 1 (1) | 0 | 1.000 |
Adjunctive gastrectomy after ESD | 11 (9.4) | 66 (7.1) | 0.374 | 10 (10) | 5 (5.2) | 0.175 |
Data are presented as number (%) or median (range).
Table 2 Results of a Multivariate Logistic Regression Analysis for the Characteristics of Early Gastric Cancers Discovered after
OR | 95% CI | p-value | |
---|---|---|---|
Macroscopic type | |||
Depressed type vs elevated type | 3.80 | 2.00–7.49 | <0.0001 |
Depth of invasion | |||
Submucosa vs mucosa | 1.85 | 0.65–5.69 | 0.252 |
Adjunctive gastrectomy after ESD | |||
Necessary vs unnecessary | 1.56 | 0.40–6.43 | 0.518 |
OR, odds ratio; CI, confidence interval; ESD, endoscopic submucosal dissection.
Table 3 Comparison of the Clinicopathological Characteristics among All Patients with PGC and Those with MGC Discovered after
PGC (n=67) | MGC (n=50) | p-value | |
---|---|---|---|
Sex | 0.847 | ||
Male | 54 (81) | 41 (82) | |
Female | 13 (19) | 9 (18) | |
Age, yr | 69 (46–85) | 74 (56–90) | 0.003 |
Time after | 4.9 (1.0–15.0) | 3.8 (1.0–14.0) | 0.263 |
Time after latest negative endoscopy, yr | 1.9 (0.5–10.0) | 1.0 (0.5–2.0) | <0.0001 |
Location | 0.627 | ||
Upper | 15 (23) | 9 (18) | |
Middle | 27 (40) | 18 (36) | |
Lower | 25 (37) | 23 (46) | |
Macroscopic type | 0.049 | ||
Elevated type | 11 (16) | 16 (32) | |
Depressed type | 56 (84) | 34 (68) | |
Size (diameter), mm | 14 (3–75) | 11 (2–43) | 0.014 |
Histology | 1.000 | ||
Differentiated type | 65 (97) | 49 (98) | |
Undifferentiated type | 2 (3) | 1 (2) | |
Depth of invasion | 0.473 | ||
Mucosa | 57 (85) | 40 (80) | |
Submucosa | 10 (15) | 10 (20) | |
Ulceration or scar | 5 (7.5) | 6 (12) | 0.408 |
Lymphatic invasion | 2 (3) | 5 (10) | 0.136 |
Venous invasion | 0 | 2 (4) | 0.281 |
Adjunctive gastrectomy after ESD | 4 (6) | 7 (14) | 0.201 |
Data are presented as number (%) or median (range).
PGC, primary gastric cancer; MGC, metachronous gastric cancer; ESD, endoscopic submucosal dissection.