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Improved Curative Resection Rates of Early Gastric Cancers By Endoscopic Mucosal Resection (EMR) Using Endoscopic Submucosal Dissection Method (ESD)
Abstracts
M1380 Long Term Prognosis of the Cases After EMR of Early Gastric Cancer Atsushi Mitsunaga, Ryujirou Imai, Ichirou Ishikawa, Izumi Shirato, Shohei Shimizu, Hiroyuki Konishi, Shinichi Nakamura, Itaru Ohi, Keiko Shiratori Aim: There have been passed about 20 years after starting to perform the endoscopic mucosal resection (EMR) for early gastric cancer. Then we studied the long term prognosis of the cases after EMR. Method: Seven hundred and seventeen cases (814 lesions) were entre´e for this study. Those cases were performed EMR between 1983 and 2003, and followed up more over two years. Results: Six hundred and eight lesions (74.7%) were indicated cases and 206 lesions (25.3%) were contraindicated cases (indication was according to the guide line of Japanese Gastric Cancer Association). Thirty-two point nine percent of the contraindicated lesions were the cases of over 75 years old that were 24.6% of the whole cases. Ninety-six point five percent were differentiated lesions and the undifferentiated lesions were only 3.5% of all lesions. The cases of EMR for early gastric cancer have increased gradually but the mean age of the patients, which was about 70 years old, has never changed within this interval. The mean interval of the surveillance after EMR was 4 years and 9 months (min 2 years, max 19 years and 9 months). The planned surveillance after EMR was especially difficult in the aged patients. Heterogeneous early gastric cancer has occur in 4% of the whole cases and the relative risk of the heterogeneous early gastric cancer occurring was 3.42 in the simultaneous early gastric cancer cases. We could find about 50% of the heterogeneous early gastric cancer near by the first lesion. There was no difference in the prognosis after EMR between over 75 years patients and less than 75 years patients on the Kaplan-Meier survival curve excluding the death of complication. And there was no case of surgical operation due to the complication of EMR (containing 6 perforation cases) in all patients. Conclusion: Considering about there is no difference of the mean age of the EMR cases of early gastric cancer in spite of the tendency of aging of Japanese population, we are thinking that differentiated gastric cancer has occurred after some settled interval because such cancer grows in the atrophic mucosa after Helicobacter pylori infection. Heterogeneous multiple gastric cancer has occur in 4% cases after EMR of early gastric cancer, so it is suitable to follow continuously especially in the simultaneous multiple gastric cancer case at the first EMR. Even if in the aged patients, the prognosis after EMR for early gastric cancer was not different from the patient’s prognosis less than 75 years old. So considering about the QOL after EMR, we are thinking that especially the aged patients should take the benefit of EMR for the treatment of early gastric cancer.
M1381 Genetic Markers to Identify High Risk Patients for Multiple Early Gastric Cancers After Treatment with Endoscopic Mucosal Resection Mayumi Fukuda, Kazuhide Higuchi, Hiroshi Yokozaki, Tetsuya Tanigawa, Masatsugu Shiba, Toshio Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara, Shinei Oshitani, Tetsuo Arakawa Purpose: Due to advances in endoscopic therapeutic techniques such as mucosal resection, gastric cancers have usually been treated at an early stage. However, multiple gastric cancers are observed in approximately 3.7-5.7% of all patients with gastric cancer. It is very important to find predictive factors of multiple gastric cancers after endoscopic resection. Microsatellite instability (MSI) due to defects in mismatch repair genes is recognized as an important mechanism in tumorigenesis. In addition, epigenetic silencing of promoter hypermethylation of tumor suppressor or tumor-related genes has emerged recently as one of the pivotal genetic alterations in cancer development. To find out genetic markers to identify high risk patients for multiple early gastric cancers after endoscopic resection, we analyzed MSI and the methylation status of multiple tumor-related genes in patients with multiple gastric cancers. Materials and Methods: Sixty-four adenocarcinomas resected by endoscopy, including 32 solitary tumors from 32 patients and 32 multiple tumors from 14 patients, were employed. We analyzed MSI and the methylation status of promoter regions of the hMLH1, MGMT, p16 and E-cadherin using methylation-specific PCR. Expression levels of hMLH1 were examined by immunohistochemistory. Results: In early multiple gastric cancers (MGCs), MSI was observed in 5 of 14 patients (35.7%) and in 7 of 32 cancers (21.9%). On the other hand, in early solitary gastric cancers (SGCs), MSI was observed in only 3 of 32 cancers (9.3%). Significant differences were obsereved between the 2 groups (p ! 0.001, p Z 0.02). Patients with MSI (C) gastric cancer tended to develop a secondary gastric cancer frequently in comparison with patients with MSI (-) gastric cancer. Promoter hypermethylation of hMLH1, MGMT, p16 and E-cadherin was found in 15.6%, 40.6%, 21.9%, and 21.9% of SGCs, and in 31.3%, 37.5%, 25.0%, and 18.8% of MGCs, respectively. Hypermethylation of hMLH1 was more frequently observed in MGCs than in SGCs (p ! 0.01), whereas there was no significant difference between average number of methylated genes in SGCs and in MGCs. Conclusions: Our results indicate that hMLH1 is one of the frequent methylation targets in MGCs and that inactivation of hMLH1 through promoter hypermethylation may be involved in the development of multiple gastric cancers following the MSI pathway. Patients with promoter hypermethylation of hMLH1 will need to be closely observed by endoscopy as high risk patients for multiple early gastric cancers even if the endoscopic resection were successful.
www.giejournal.org
M1382 Improved Curative Resection Rates of Early Gastric Cancers By Endoscopic Mucosal Resection (EMR) Using Endoscopic Submucosal Dissection Method (ESD) Masaru Odashima, Michiro Otaka, Mario Jin, Isao Wada, Youhei Horikawa, Tamotsu Matsuhashi, Reina Ohba, Natsumi Hatakeyama, Jinko Oyake, Sumio Watanabe Background: EMR is now accepted as one of the standard treatment for early gastric cancers with low probability of lymph node metastasis. Although, the basic EMR techniques are strip biopsy method and cap method, the chance of local recurrence after EMR remains problem if the resection margin is not clear. Because the benefit of EMR can be achieved only through careful histologic examination, an en-block resection is recommended. Aims: In order to resect mucosal cancers perfectly, endoscoipc submucosal dissection EMR (ESD) using insulation tipped diathermic knife (IT knife) and hook knife was performed for early gastric cancers in the last 4 years in our hospital. Method: EMR was applied to patients with early gastric cancers up to 20 mm in diameter that were of a well or moderately histologically differentiated type, and superficially elevated and/or depressed type (type I, IIa, and IIc) without ulceration. Results: Eighty patients were treated by basic EMR procedure from 1994 to 2004. The rate of EA resection (which means curative resection) was 51.3% (41/80), and additional operations were performed in 8 patients (10%). Since ESD procedure was used, 57 patients were treated with ESD. The rate of EA resection was 75.4% (43/57), and additional operations were performed in 6 patients (9%) because of depth of the tumors. There were no gastric cancer related deaths during follow up period. Conclusion: EMR treatment for early gastric cancer by submucosal dissection (ESD) method using IT knife and hook knife is feasible and effective technique.
M1383 Healing Rate and Related Factors of Endoscopic Submucosal Dissection(ESD)-Induced Ulcer After Pantoprazol Therapy for 4 Week Tae-Hoon Oh, Hwoon-Yong Jung, Kee Don Choi, Gin H. Lee, Ja Young Kim, Kwi-Sook Choi, Hyung Joon Lee, Jun-Won Chung, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Jin-Ho Kim Background/Aims: Although artificial ulcer caused by ESD is thought to heal faster and to recur less often than non-iatrogenic peptic ulcer. There is no consensus regarding healing degree of ESD-induced ulcer and optimal duration of PPI treatment. This study retrospectively evaluated healing rate and related factors of ESD-induced ulcer after pantoprazol therapy for 4 week. Methods: A total of 56 patients who have underwent ESD for adenoma or early stage gastric cancer and performed follow-up endoscopy at 4 week were included. Pantoprazol (40 mg per day) were given to these patient during 4 week. We compared the each size and relevant factors to healing degree of ulcer including age, sex, procedure time, location of neoplasm, presence of complication, comorbidity, drug history such as aspirin or NSAIDs and pathologic diagnosis between initial ESD-induced ulcer and one at 4 week later. Results: Median age was 62 (range: 45-87), sex ratio was 5.6: 1 (male to female), median size of tumor was 15 mm (range: 3-93), median size of initial specimen were 1588 mm2 (range: 5-95), median size of ESD-induced ulcer at 4 week was 11 mm2 (range: 0-30). 28(50%) patients had small ulcer (diameter ! 3 mm) on the follow-up endoscopy at 4 week. The size corresponding to root area of ESD-induced ulcer at 4 week was closely correlated with that of initial specimen (p ! 0.001). Initial ESD-induced ulcer which was less than 3 cm in diameter was almost included in small ulcer group at 4 week, but ulcer size at 4 week abruptly increased at the point of 4 cm in diameter of initial ulcer. Procedure time and initial specimen size were significantly associated with healing rate (p ! 0.001). But the only parameter which had significant value in multivariate analysis was specimen size (initial ulcer size). Conclusions: Healing rate of ESD-induced ulcer at 4 week is depending on the initial ulcer size. Initial ESD-induced ulcer which is larger than 4 cm in diameter should be treated with PPI for more than 4 week.
Volume 63, No. 5 : 2006 GASTROINTESTINAL ENDOSCOPY AB187
M1380 Long Term Prognosis of the Cases After EMR of Early Gastric Cancer Atsushi Mitsunaga, Ryujirou Imai, Ichirou Ishikawa, Izumi Shirato, Shohei Shimizu, Hiroyuki Konishi, Shinichi Nakamura, Itaru Ohi, Keiko Shiratori Aim: There have been passed about 20 years after starting to perform the endoscopic mucosal resection (EMR) for early gastric cancer. Then we studied the long term prognosis of the cases after EMR. Method: Seven hundred and seventeen cases (814 lesions) were entre´e for this study. Those cases were performed EMR between 1983 and 2003, and followed up more over two years. Results: Six hundred and eight lesions (74.7%) were indicated cases and 206 lesions (25.3%) were contraindicated cases (indication was according to the guide line of Japanese Gastric Cancer Association). Thirty-two point nine percent of the contraindicated lesions were the cases of over 75 years old that were 24.6% of the whole cases. Ninety-six point five percent were differentiated lesions and the undifferentiated lesions were only 3.5% of all lesions. The cases of EMR for early gastric cancer have increased gradually but the mean age of the patients, which was about 70 years old, has never changed within this interval. The mean interval of the surveillance after EMR was 4 years and 9 months (min 2 years, max 19 years and 9 months). The planned surveillance after EMR was especially difficult in the aged patients. Heterogeneous early gastric cancer has occur in 4% of the whole cases and the relative risk of the heterogeneous early gastric cancer occurring was 3.42 in the simultaneous early gastric cancer cases. We could find about 50% of the heterogeneous early gastric cancer near by the first lesion. There was no difference in the prognosis after EMR between over 75 years patients and less than 75 years patients on the Kaplan-Meier survival curve excluding the death of complication. And there was no case of surgical operation due to the complication of EMR (containing 6 perforation cases) in all patients. Conclusion: Considering about there is no difference of the mean age of the EMR cases of early gastric cancer in spite of the tendency of aging of Japanese population, we are thinking that differentiated gastric cancer has occurred after some settled interval because such cancer grows in the atrophic mucosa after Helicobacter pylori infection. Heterogeneous multiple gastric cancer has occur in 4% cases after EMR of early gastric cancer, so it is suitable to follow continuously especially in the simultaneous multiple gastric cancer case at the first EMR. Even if in the aged patients, the prognosis after EMR for early gastric cancer was not different from the patient’s prognosis less than 75 years old. So considering about the QOL after EMR, we are thinking that especially the aged patients should take the benefit of EMR for the treatment of early gastric cancer.
M1381 Genetic Markers to Identify High Risk Patients for Multiple Early Gastric Cancers After Treatment with Endoscopic Mucosal Resection Mayumi Fukuda, Kazuhide Higuchi, Hiroshi Yokozaki, Tetsuya Tanigawa, Masatsugu Shiba, Toshio Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara, Shinei Oshitani, Tetsuo Arakawa Purpose: Due to advances in endoscopic therapeutic techniques such as mucosal resection, gastric cancers have usually been treated at an early stage. However, multiple gastric cancers are observed in approximately 3.7-5.7% of all patients with gastric cancer. It is very important to find predictive factors of multiple gastric cancers after endoscopic resection. Microsatellite instability (MSI) due to defects in mismatch repair genes is recognized as an important mechanism in tumorigenesis. In addition, epigenetic silencing of promoter hypermethylation of tumor suppressor or tumor-related genes has emerged recently as one of the pivotal genetic alterations in cancer development. To find out genetic markers to identify high risk patients for multiple early gastric cancers after endoscopic resection, we analyzed MSI and the methylation status of multiple tumor-related genes in patients with multiple gastric cancers. Materials and Methods: Sixty-four adenocarcinomas resected by endoscopy, including 32 solitary tumors from 32 patients and 32 multiple tumors from 14 patients, were employed. We analyzed MSI and the methylation status of promoter regions of the hMLH1, MGMT, p16 and E-cadherin using methylation-specific PCR. Expression levels of hMLH1 were examined by immunohistochemistory. Results: In early multiple gastric cancers (MGCs), MSI was observed in 5 of 14 patients (35.7%) and in 7 of 32 cancers (21.9%). On the other hand, in early solitary gastric cancers (SGCs), MSI was observed in only 3 of 32 cancers (9.3%). Significant differences were obsereved between the 2 groups (p ! 0.001, p Z 0.02). Patients with MSI (C) gastric cancer tended to develop a secondary gastric cancer frequently in comparison with patients with MSI (-) gastric cancer. Promoter hypermethylation of hMLH1, MGMT, p16 and E-cadherin was found in 15.6%, 40.6%, 21.9%, and 21.9% of SGCs, and in 31.3%, 37.5%, 25.0%, and 18.8% of MGCs, respectively. Hypermethylation of hMLH1 was more frequently observed in MGCs than in SGCs (p ! 0.01), whereas there was no significant difference between average number of methylated genes in SGCs and in MGCs. Conclusions: Our results indicate that hMLH1 is one of the frequent methylation targets in MGCs and that inactivation of hMLH1 through promoter hypermethylation may be involved in the development of multiple gastric cancers following the MSI pathway. Patients with promoter hypermethylation of hMLH1 will need to be closely observed by endoscopy as high risk patients for multiple early gastric cancers even if the endoscopic resection were successful.
www.giejournal.org
M1382 Improved Curative Resection Rates of Early Gastric Cancers By Endoscopic Mucosal Resection (EMR) Using Endoscopic Submucosal Dissection Method (ESD) Masaru Odashima, Michiro Otaka, Mario Jin, Isao Wada, Youhei Horikawa, Tamotsu Matsuhashi, Reina Ohba, Natsumi Hatakeyama, Jinko Oyake, Sumio Watanabe Background: EMR is now accepted as one of the standard treatment for early gastric cancers with low probability of lymph node metastasis. Although, the basic EMR techniques are strip biopsy method and cap method, the chance of local recurrence after EMR remains problem if the resection margin is not clear. Because the benefit of EMR can be achieved only through careful histologic examination, an en-block resection is recommended. Aims: In order to resect mucosal cancers perfectly, endoscoipc submucosal dissection EMR (ESD) using insulation tipped diathermic knife (IT knife) and hook knife was performed for early gastric cancers in the last 4 years in our hospital. Method: EMR was applied to patients with early gastric cancers up to 20 mm in diameter that were of a well or moderately histologically differentiated type, and superficially elevated and/or depressed type (type I, IIa, and IIc) without ulceration. Results: Eighty patients were treated by basic EMR procedure from 1994 to 2004. The rate of EA resection (which means curative resection) was 51.3% (41/80), and additional operations were performed in 8 patients (10%). Since ESD procedure was used, 57 patients were treated with ESD. The rate of EA resection was 75.4% (43/57), and additional operations were performed in 6 patients (9%) because of depth of the tumors. There were no gastric cancer related deaths during follow up period. Conclusion: EMR treatment for early gastric cancer by submucosal dissection (ESD) method using IT knife and hook knife is feasible and effective technique.
M1383 Healing Rate and Related Factors of Endoscopic Submucosal Dissection(ESD)-Induced Ulcer After Pantoprazol Therapy for 4 Week Tae-Hoon Oh, Hwoon-Yong Jung, Kee Don Choi, Gin H. Lee, Ja Young Kim, Kwi-Sook Choi, Hyung Joon Lee, Jun-Won Chung, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Jin-Ho Kim Background/Aims: Although artificial ulcer caused by ESD is thought to heal faster and to recur less often than non-iatrogenic peptic ulcer. There is no consensus regarding healing degree of ESD-induced ulcer and optimal duration of PPI treatment. This study retrospectively evaluated healing rate and related factors of ESD-induced ulcer after pantoprazol therapy for 4 week. Methods: A total of 56 patients who have underwent ESD for adenoma or early stage gastric cancer and performed follow-up endoscopy at 4 week were included. Pantoprazol (40 mg per day) were given to these patient during 4 week. We compared the each size and relevant factors to healing degree of ulcer including age, sex, procedure time, location of neoplasm, presence of complication, comorbidity, drug history such as aspirin or NSAIDs and pathologic diagnosis between initial ESD-induced ulcer and one at 4 week later. Results: Median age was 62 (range: 45-87), sex ratio was 5.6: 1 (male to female), median size of tumor was 15 mm (range: 3-93), median size of initial specimen were 1588 mm2 (range: 5-95), median size of ESD-induced ulcer at 4 week was 11 mm2 (range: 0-30). 28(50%) patients had small ulcer (diameter ! 3 mm) on the follow-up endoscopy at 4 week. The size corresponding to root area of ESD-induced ulcer at 4 week was closely correlated with that of initial specimen (p ! 0.001). Initial ESD-induced ulcer which was less than 3 cm in diameter was almost included in small ulcer group at 4 week, but ulcer size at 4 week abruptly increased at the point of 4 cm in diameter of initial ulcer. Procedure time and initial specimen size were significantly associated with healing rate (p ! 0.001). But the only parameter which had significant value in multivariate analysis was specimen size (initial ulcer size). Conclusions: Healing rate of ESD-induced ulcer at 4 week is depending on the initial ulcer size. Initial ESD-induced ulcer which is larger than 4 cm in diameter should be treated with PPI for more than 4 week.
Volume 63, No. 5 : 2006 GASTROINTESTINAL ENDOSCOPY AB187