Gastrointestinal Intervention 2016; 5(1): 1-5
Published online March 31, 2016 https://doi.org/10.18528/gii150024
Copyright © International Journal of Gastrointestinal Intervention.
Xian Feng Xia, and Philip Wai Yan Chiu*
Department of Surgery, CUHK Jockey Club Minimally Invasive Surgical Skills Center, Institute of Digestive Disease and State Key Laboratory of Gastrointestinal Diseases, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
Correspondence to:*Corresponding author. Department of Surgery, Prince of Wales Hospital, 30-32, Ngan Shing Street, Shatin, N.T., Hong Kong SAR, China.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gastric cancer remained second commonest cancer worldwide. The diagnosis of early gastric cancer (EGC) is increasing in Japan and South Korea resulting in better oncological outcomes. Endoscopic resection (ER) is safe and effective treatment for EGC with minimal risk of lymph node metastasis. The oncological clearance of ER for EGC in expanded criteria remains controversial. Several retrospective studies showed that endoscopic submucosal dissection (ESD) achieved minimal local recurrence and excellent survival for EGC in expanded indications. With an increasing trend of cancer occuring in the aging population, ER will play a major role in treatment of EGC among elderly who usually have multiple comorbidities. Salvage gastrectomy is generally recommended for those with non-curative ESD, while further researches should be conducted to refine the risks of nodal metastasis for various submucosal EGCs. Endoscopic surveillance is recommended for long term follow-up of patients after curative ESD as the risk of metachronous cancer is significant. Eradication of
Keywords: Early gastric cancer, Endoscopic resection, Endoscopic submucosal dissection
Early gastric cancer (EGC) is defined as carcinoma involving the mucosa and submucosa irrespective of lymph node status. The prevalence of EGC is up to 60% in Japan and South Korea, mainly because of the nationwide gastric cancer screening program conducted for residents aged 40 years or above in both countries. Endoscopic resection (ER) has become the standard of treatment for intramucosal EGC with minimal risk of nodal metastasis, but there is a wide variation worldwide on application of ER for treatment of EGC.
ER appeared to be the preferred treatment for EGC compared with conventional radical gastrectomy as it is a curative intent minimally invasive treatment, and the stomach can be preserved (Table 1).1?5 Our previous case cohort study showed that patients receiving endoscopic submucosal dissection (ESD) for treatment of EGC could achieve a shorter median hospital stay and lower complication rate than those receiving gastrectomy.5 However, controversies abound upon certain aspects of ER for treatment of EGC.6 In this review, we will discuss the indications of ER for EGC, and current concerns for the expanded indication, ER for elderly patients, and the need of surveillance for metachronous cancer.
Japanese Gastric Cancer Association had established guidelines for endoscopic management of EGC.7 Conventionally, only differentiated-type intramucosal cancer less than 2cm in diameter with no ulceration is absolutely indicated for ER. In light of the histological analyses for large numbers of surgical specimens, patients meeting the absolute indication is predicted to have negligible risk of lymph node metastasis.8
However, clinical experiences demonstrated that some patients with intramucosal EGC larger than 2 cm showed no nodal metastasis. Resecting the stomach may become obsolete for these cases if the risk of nodal metastasis can be refined. By reviewing a large number of surgical cases who underwent gastrectomy for EGC, Gotoda et al9 clarified that the risk of lymph node metastasis is minimal among four groups of EGC: (1) well-differentiated intramucosal cancers less than 30-mm diameter without lymphovascular permeation regardless of ulceration; (2) well-differentiated intramucosal cancers without lymphovascular permeation and ulceration regardless of tumor size; (3) well-differentiated adenocarcinoma less than 30-mm diameter with minute submucosal invasion (SM1, lesions invade into the submucosa less than 500 μm) and without lymphovascular permeation; and (4) undifferentiated intramucosal lesions less than 20 mm in diameter without ulceration and lymphovascular permeation. Basing on these results, the indication of ER for EGC had expanded to include these categories.
To date, the validity of expanded indication for EGC remains controversial. One of the main concerns is the prediction of risk of lymph node metastasis for EGC in the expanded indication. Jee et al20 reviewed the 669 EGC patients who had surgical treatment. They found a rate of 2.3% for lymph node metastasis in patients with mucosal cancer who met the expanded indication, and 4% in patients with submucosal cancer who met the expanded indication. Meanwhile for 169 patients with well differentiated mucosal cancers without ulceration, no lymph node metastasis was found irrespective of lesion size. These data supported that well differentiated mucosal cancer of any size without ulceration can be considered as the expanded indication for ER. However, cautions should be paid for the other expanded indication since ER may carry a rate of 2.8% for lymph node metastasis in those patients.
Kim et al1 compared the outcomes of ER to surgery for treatment of EGC under the expanded indication. Although 5-year gastric cancer recurrence rate was higher for ER than for surgery (4.8% vs 0.3%,
The clinical and oncological outcomes for EGCs treated by ER in expanded criteria were compared to those in the absolute indication. With a median follow-up period of 32 months, Ahn et al19 reported that EGC in absolute indication had a higher complete resection rate (95.9% vs 88.4%,
Based on the current evidence with respect to clinical and oncologic outcomes, ESD is a feasible treatment for EGC in the expanded criteria. However, regular endoscopic surveillance should be warranted to detect the early cancer recurrence.
According to Japanese Gastric Cancer Treatment guidelines, undifferentiated EGC is recommended for ER only if there is no ulcer, intramucosal and less than 20 mm in size, as the risk of nodal metastasis is significant especially when the presence of lymphovascular permeation.17 Recently, there are reports showing enlightening results on ER for selected undifferentiated gastric cancers.21,22 Oka et al23 retrospectively reviewed 84 patients with undifferentiated EGC. ESD was found to achieve a significantly higher complete resection rate than EMR (89% vs 54%,
The safe practice of ESD required advanced endoscopic skills and appropriate training. ESD certainly carried higher risk of complications including bleeding and perforation than EMR. When compared to gastrectomy, ESD achieved better perioperative outcomes and quicker recovery as it does not involve gastrointestinal anastomosis and cutaneous incision. There will be significant advantages in treatment of EGC by ESD among elderly patients with multiple comorbidities, especially for those with comorbidities of heart and lung diseases.24 Park et al3 conducted a propensity-matched analysis including 518 EGC patients aged > 70 years and compared clinical and oncologic outcomes of ESD to surgery. All the patients had EGC meeting expanded criteria for ER. The ESD group demonstrated a shorter hospital stay than gastrectomy, while the total adverse events did not differ. Those receiving ESD had a higher incidence of metachronous lesions detected during follow-up (11.1% vs 1.7%; 17.6?24.2 months). Although the 3-year adenoma- and cancer-free survival was superior in surgery compared with ESD treatment (96.3% vs 80.0%,
In general, salvage gastrectomy with standard lymph node dissection is recommended after non-curative ER for EGC to achieve curative surgical resection for non-curative ER beyond expanded criteria.14 However, the decision to salvage surgery is usually more complex for elderly patients who often had concomitant diseases and high risks for surgery. In 2011, Kusano et al25 reported the long-term survival data in an elderly patient (> 75 years old) cohort study. The overall and disease-free survival in patients under curative ER and those who had non-curative ER with salvage gastrectomy were the same. However, a significant difference in overall and disease-free survival was found between patients with curative ER and those who had non-curative ER without salvage gastrectomy (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.08?3.28; HR 2.30, 95% CI 1.35?3.94). Furthermore, with the classification of the high risk of lymph node metastasis (“positive lymphatic or/and venous invasion” or “submucosal deep (SM2) invasion”), the 5-year survival rate was only 52% in patients who had non-curative ER without salvage gastrectomy which was significantly lower than the rate of 96% in patients who had non-curative with salvage gastrectomy. Hence salvage gastrectomy after non-curative ER should be performed for elderly patients who can tolerate the surgical procedure.
The benefits of ER with preservation of the organs of origin for the carcinoma of stomach will certainly lead to higher risk of development for metachronous gastric cancers.3 Indeed there is a higher incidence of metachronous gastric cancer after ER (2.9%?14.0%) compared with gastrectomy (1.8%?2.4%). The Japanese Society for Helicobacter Research recommends
However, the study reported by Maehata et al29 found that eradication of
Overall, the risk of metachronous gastric cancer seems to be decreased after
ER is the current standard of treatment for intramucosal EGC. Recent studies demonstrated the effectiveness of ESD to achieve oncological clearance for EGC in the category of expanded criteria with favorable long term. One of the main concerns is the differentiation of patients with high risk of lymph node metastasis under expanded criteria for ER and further research is warranted to delineate risk and to identify predictors of nodal metastasis. For the increasing elderly population with concomitant diseases and higher risks of surgical complications, ESD will serve as excellent curative treatment for EGCs. After ESD, regular surveillance endoscopy should be performed to detect metachronous cancer.
Endoscopic Resection Compared with Traditional Gastrectomy for T1 Early Gastric Cancer
Study | Country | Study design | Patients and intervention | No. of subjects (ER vs surgery) | Length of follow-up | Survival rate (ER vs surgery) | Tumor recurrence (ER vs surgery) | Complication rate (ER vs surgery) |
---|---|---|---|---|---|---|---|---|
Kim et al1 (2015) | South Korea | Retrospective | Patients meeting expanded indication for ER or surgery | 165/292 | Median 58.6 mo | 97.5% vs 97.0%, | 5-yr gastric cancer recurrence rate: 4.8% vs 0.3%, | 5.5% vs 6.8%, |
Choi et al2 (2015) | South Korea | Retrospective | Patients meeting absolute indication for ER or surgery | 261/114 | Median 76.4 mo | 95.7% vs 93.6%, | Metachronous cancer incidence: 6.1% vs 0.9%, | 2.7% vs 7.9%, |
Park et al3 (2014) | South Korea | Retrospective | Elderly patients (aged ≥ 70 yr) underwent ESD or surgery | 132/132† | Median 17.6 mo in ESD, 24.2 mo in surgery ( | 97.4% vs 96.1%, | Metachronous cancer incidence: 11.1% vs 1.7%, | 5.3% vs 9.8%, |
Kim et al4 (2014) | South Korea | Retrospective | Patients underwent ESD or gastrectomy | 142/71 | Mean 76.7 ± 16.5 mo in ESD, 65.5 ± 16.5 mo in surgery ( | Overall survival: 93.4 ± 3.2 vs 85.8 ± 5.5 mo for AI, 100.5 ± 1.3 vs 84.9 ± 2.6 mo for EI, | Recurrence: 4.7% vs 0%, | 8.5% vs 28.2%, |
Chiu et al | Hong Kong | Retrospective | Patients underwent ESD or gastrectomy | 74/40 | Median 27 mo in ESD, 77.6 mo in surgery, | 94.6% vs 89.7%, | NA | 5.4% vs 32.5%, |
ER, endoscopic resection; ESD, endoscopic submucosal dissection; AI, absolute indication; EI, expanded indication; NA, not available.
†Propensity-matched analysis.
‡Patients confined within expanded indications.
Follow-Up Data of Endoscopic Resection for Early Gastric Cancer Meeting Absolute vs Expanded Indications
Study | Country | Study design | Intervention | No. of subjects (AI/EI) | Length of follow-up | Curative resection rate (AI vs EI) | Incidence of metachronous cancer (AI vs EI) | Survival data (AI vs EI) |
---|---|---|---|---|---|---|---|---|
Choi et al10 (2015) | South Korea | Retrospective | ESD, EMR | 469/348 | Mean 48.3 ± 20.2 mo | 94.9% vs 87.1%, | 5.8% vs 7.8%, | 5-yr survival rate: 96.6% vs 94.2%, |
Nakamura et al11 (2015) | Japan | Retrospective | ESD | 783/378 | Median 29.5 mo | 96.4% vs 93.4%, | NA | 5-yr survival rate: 95.64% vs 90.49%, |
Kang et al12 (2015) | South Korea | Retrospective | ESD | 84/174 | Mean 74.8 ± 20.7 mo | 96.4% vs 78.7%, | NA | 5-yr disease-free survival rate: 98.2% vs 98.5% |
Shin et al13 (2015) | South Korea | Retrospective | ESD | 517/588 | Median 32 mo | 91.1% vs 91.3%, | NA | 3-yr survival rate: 99.0% vs 98.6%, |
Ohnita et al14 (2014) | Japan | Retrospective | ESD | 617/507 | Median 66 mo | 96.6% vs 91.5%, | NA | 5-yr survival rate: |
Oda et al15 (2014) | Japan | Retrospective | ESD | 1,601/1,205† | > 5 yr | - | NA | Gastric cancer-related death: 0.19% vs 0.33% |
Kosaka et al16 (2014) | Japan | Retrospective | ESD | 297/107 | Range 5?9 yr | 96.0% vs 72.0%, | 6.4% vs 13.1%, | 5-yr survival rate: |
Park et al17 (2013) | South Korea | Retrospective | ESD | 354/562 | Median 24.1 mo in AI, 30.0 mo in EI | 94.8% vs 89.9%, | 1.1% vs 3.5%, | Disease-free survival duration: 70.1 ± 2.9 mo vs 61.7 ± 1.2 mo, |
Lee et al18 (2011) | South Korea | Retrospective | ESD | 595/211 | Median 26 mo | 97.3% vs 81.0%, | 3.6% vs 3.3%, | 1-yr disease-free rate: 98% vs 99%, |
Ahn et al19 (2011) | South Korea | Retrospective | ESD, EMR | 767/477 | Median 32 mo | 95.9% vs 88.4%, | 3.7% vs 7.2%, | 3-yr local recurrence-free rate: 98.8%?99.0% vs 98.5%, |
AI, absolute indication; EI, expanded indication; ESD, endoscopic submucosal dissection; EMR, endoscopic mucosal resection; NA, not available.
†All enrolled cases with curative resection.
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