Decision to perform additional surgery after non-curative endoscopic submucosal dissection for gastric cancer based on the risk of lymph node metastasis: a long-term follow-up study.

BACKGROUND: Radical surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may be excessive, since only 5-10% of patients have lymph node metastasis (LNM). This study investigated the suitability of the eCura system for determining the need for radical surgery after non-curative ESD. METHODS: We retrospectively investigated 343 patients who underwent non-curative ESD for EGC from 2006 to 2021 at a tertiary hospital in Korea. These patients were divided into surgery (n = 191) and observation (n = 152) groups based on whether they underwent additional surgery post-ESD. Each group was further classified into low-risk (eCura score 0-1), intermediate-risk (eCura score 2-4) and high-risk (eCura score 5-7). All patients were regularly followed-up at least annually after the initial treatment. The cumulative overall and recurrence-free survival rates were calculated for each category and compared between the surgery and observation groups. RESULTS: No significant differences in overall survival were found between the surgery and observation groups in low-risk (p = 0.168) and intermediate-risk patients (p = 0.306); however, high-risk patients had better 5-year overall survival rate in the surgery group than in the follow-up group (95.2% vs. 71.4%, p < 0.001). The 5-year recurrence-free survival rate was higher in the surgery group than in the observation group for low-risk (100% vs. 84.3%; p = 0.034), intermediate-risk (96.1% vs. 88.4%; p = 0.081) and high-risk patients (100% vs. 83.3%; p = 0.023). CONCLUSIONS: Follow-up without additional surgery after non-curative ESD can be a reasonable option for low-risk and even intermediate-risk patients according to the eCura system. However, surgery is warranted for eCura high-risk patients.

Predictive Factors for Short-Term Survival after Non-Curative Endoscopic Submucosal Dissection for Early Gastric Cancer.

BACKGROUND/AIMS: For early gastric cancer (EGC) treated using endoscopic submucosal dissection (ESD) with poor curability defined by the Japanese Guidelines (non-curative EGC, N-EGC), additional gastrectomy has been recommended. However, N-EGC patients without additional gastrectomy often die of other diseases within a relatively short interval after ESD. It has been unclear whether additional gastrectomy is beneficial or not for such patients. The aim of this study was to clarify predictors for short-term survival of N-EGC patients without additional gastrectomy after ESD. METHODS: One hundred six N-EGC patients without additional gastrectomy were included in this study. Factors related to short-term survival, defined as death within 3 years after ESD, were evaluated using uni- and multivariate analyses by comparing patients with and without short-term survival (Groups S and C, respectively). RESULTS: During the mean follow-up period of 89 months, 39 patients died (14 patients died within 3 years, being Group S). The cause of death was gastric cancer for only 1 patient in the Group C. The 3- and 5-year overall survival rates were 86.8 and 81.8%, respectively, and the 3- and 5-years disease-specific survival rates were 100 and 98.9%, respectively. Univariate analyses showed that short-term survival was statistically associated with elevated morphology, high-risk status for lymph node metastases as defined by the eCura system, severe comorbidity (Charlson Comorbidity Index [CCI] ≥3), low level of activity in daily living (being unable to go out by oneself), habitation (a nursing home), and several poor nutritional prognostic indices (neutrophil to lymphocyte ratio ≥2.5, geriatric nutritional risk index <92, C-reactive protein ≥1.0). In the multivariate analysis, a high CCI (≥3) was the independent predictor for short-term survival after ESD (odds ratio, 8.1; 95% confidence interval, 1.53-43.0; p = 0.014). CONCLUSIONS: Severe comorbidity indicated by a high CCI score (≥3) was the independent predictor for short-term survival for EGC patients without additional gastrectomy after non-curative ESD. Since the cause of death for most patients was not gastric cancer, observational follow-ups without additional gastrectomy might be a reasonable option for patients with a poor general status indicated by a CCI ≥3.

Is the eCura system useful for selecting patients who require radical surgery after noncurative endoscopic submucosal dissection for early gastric cancer? A comparative study.

BACKGROUND: We have established a risk-scoring system, termed the "eCura system," for the risk stratification of lymph node metastasis in patients who have received noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to clarify whether this system contributes to the selection of patients requiring radical surgery after ESD. METHODS: Between 2000 and 2011, 1,969 patients with noncurative ESD for EGC were included in this multicenter study. Depending on the treatment strategy after ESD, we had patients with no additional treatment (n = 905) and those with radical surgery after ESD (n = 1,064). After the application of the eCura system to these patients, cancer recurrence and cancer-specific mortality in each risk category of the system were compared between the two patient groups. RESULTS: Multivariate Cox analysis revealed that in the high-risk category, cancer recurrence was significantly higher (hazard ratio = 3.13, p = 0.024) and cancer-specific mortality tended to be higher (hazard ratio = 2.66, p = 0.063) in patients with no additional treatment than in those with radical surgery after ESD, whereas no significant differences were observed in the intermediate-risk and low-risk categories. In addition, cancer-specific survival in the low-risk category was high in both patient groups (99.6 and 99.7%). A limitation of this study is that it included a small number of cases with undifferentiated-type EGC (292 cases). CONCLUSIONS: The eCura system is a useful aid for selecting the appropriate treatment strategy after noncurative ESD for EGC. However, caution is needed when applying this system to patients with undifferentiated-type EGC.

Clinical outcomes and risk factors of non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective multicenter study in Zhejiang, China.

Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD. Methods: We conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system". Results: Among 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively). Conclusion: Clinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.

Treatment strategy after noncurative endoscopic resection for early gastric cancers in patients aged ≥ 85 years: a multicenter retrospective study in a highly aged area of Japan.

BACKGROUND: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area. METHODS: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment. RESULTS: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years). CONCLUSIONS: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs.

Determination of Additional Surgery after Non-Curative Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Practically Modified Application of the eCura System.

BACKGROUND: Additional surgery after non-curative endoscopic submucosal dissection (ESD) may be excessive as few patients have lymph node metastasis (LNM). It is necessary to develop a risk stratification system for LNM after non-curative ESD, such as the eCura system, which was introduced in the Japanese gastric cancer treatment guidelines. However, the eCura system requires venous and lymphatic invasion to be separately assessed, which is difficult to distinguish without special immunostaining. In this study, we practically modified the eCura system by classifying lymphatic and venous invasion as lymphovascular invasion (LVI). METHOD: We retrospectively reviewed 543 gastric cancer patients who underwent radical gastrectomy after non-curative ESD between 2006 and 2019. LNM was evaluated according to LVI as well as size >30 mm, submucosal invasion ≥500 µm, and vertical margin involvement, which were used in the eCura system. RESULTS: LNM was present in 8.1% of patients; 3.6%, 2.3%, 7.4%, 18.3%, and 61.5% of patients with no, one, two, three, and four risk factors had LNM, respectively. The LNM rate in the patients with no risk factors (3.6%) was not significantly different from that in patients with one risk factor (2.3%, p = 0.523). Among patients with two risk factors, the LNM rate without LVI was significantly lower than with LVI (2.4% vs. 10.7%, p = 0.027). Among patients with three risk factors, the LNM rate without LVI was lower than with LVI (0% vs. 20.8%, p = 0.195), although not statistically significantly. Based on LNM rates according to risk factors, patients with LVI and other factors were assigned to the high-risk group (LNM, 17.4%) while other patients as a low-risk group (LNM, 2.4%). CONCLUSIONS: Modifying the eCura system by classifying lymphatic and venous invasion as LVI successfully stratified LNM risk after non-curative ESD. Moreover, the high-risk group can be simply identified based on LVI and the presence of other risk factors.

The efficacy of the application of the curative criteria of the 5rd edition Japanese gastric cancer treatment guidelines for early adenocarcinoma of the esophagogastric junction treated by endoscopic submucosal dissection.

BACKGROUND: The curative criteria after endoscopic submucosal dissection for early gastric carcinoma were updated by the Japanese Gastric Cancer Association. No study has shown promising results with endoscopic submucosal dissection for early adenocarcinoma of esophagogastric junction based on the new curative criteria. The purpose of this study was to validate clinical efficacy of the application of the curative criteria of the 5th edition Japanese gastric cancer treatment guidelines for early adenocarcinoma of esophagogastric junction after endoscopic submucosal dissection. METHODS: Patients who underwent endoscopic submucosal dissection for Siewert type II adenocarcinoma between January 2013 and June 2018 were eligible for this study. Clinical and pathological features and treatment outcomes were retrospectively reviewed using medical records. RESULTS: The success rate for en-bloc resection was 97.2% (172/177) and the curative resection rate was 71.2% (126/177). Additional endoscopic submucosal dissection or radical surgery was conducted in 10 patients (5.6%) who did not fulfil the curative resection criteria, while one patient with curative resection remedied with endoscopic submucosal dissection because of recurrence. According to eCura scoring system, 94 patients (53.1%) were categorized into eCura A, 34 patients (19.2%) into eCura B, 11 patients (6.2%) into eCura C-1, and 38 patients (21.5%) into eCura C-2. Five patients categorized as eCura C-2 underwent radical surgery, two of whom have lymph node metastasis. CONCLUSIONS: Endoscopic submucosal dissection for early adenocarcinoma of esophagogastric junction that met the expanded criteria of the 5th edition Japanese gastric cancer treatment guidelines were acceptable and should be the standard treatment instead of surgical resection.

Endoscopic management of patients with early gastric cancer before and after endoscopic resection: A review.

With the wide application of endoscopic resection for early gastric cancer (EGC) by not only Asian endoscopists but also those from Western countries, reviews on standardized treatment processes before and after endoscopic resection are nevertheless lacking. In this article we provide a narrative review of studies on the selection of appropriate EGC for endoscopic resection and the follow-up strategies for those with histologically confirmed EGC after endoscopic resection. EGC should be comprehensively assessed before endoscopic resection, including its exact margin, invasive depth and risk of lymph node metastasis (LNM). While the curative resection status of EGC may be evaluated after endoscopic resection based on the newly developed eCura system, although this needs to be further verified. Surveillance with endoscopy and computed tomography scan is necessary for patients with an EGC level A or B. An additional endoscopic resection is recommended for patients with a level-C1 EGC. For patients with a level-C2 EGC, close follow-up is suggested for low-risk tumors of level C2 and additional surgery for those at high risks. Further postoperative strategy is suggested based on comprehensive assessment of the risk of LNM, patient's quality of life and wishes.