Non-curative Endoscopic Submucosal Dissection Research Articles

Is Radical Surgery Necessary for All Patients Diagnosed as Having Non-Curative Endoscopic Submucosal Dissection?

If a lesion does not meet the expanded indication criteria for treatment with endoscopic therapy for early gastric cancer or has a positive resection margin, it is regarded as suitable for non-curative resection. Non-curative resection is closely related to the risk of local recurrence, lymph node metastasis, and poor prognosis. If the result is confirmed as non-curative resection, additional treatment should be considered depending on the risks of residual tumor, local recurrence, and lymph node metastasis. As lymphatic invasion is the most important risk factor of recurrence and poor prognosis, surgical treatment should be considered if lymphatic invasion is present. If patients are not suitable for additional surgery owing to old age or coexisting severe disease, close surveillance can be an alternative treatment option.

Prospective Multicenter Feasibility Study of Laparoscopic Sentinel Basin Dissection after Endoscopic Submucosal Dissection for Early Gastric Cancer: SENORITA 2 Trial Protocol.

PurposeAlthough standard radical gastrectomy is recommended after noncurative resection of endoscopic submucosal dissection (ESD) for early gastric cancer in most cases, residual tumor and lymph node metastasis have not been identified after surgery. The aim of this study is to evaluate the feasibility of sentinel node navigation surgery after noncurative ESD.Materials and MethodsThis trial is an investigator-initiated, multicenter prospective phase II trial. Patients who underwent ESD for clinical stage T1N0M0 gastric cancer with noncurative resections were eligible. Qualified investigators who completed the prior phase III trial (SENORITA 1) are exclusively allowed to participate. In this study, 2 detection methods will be used: 1) intraoperative endoscopic submucosal injection of dual tracer, including radioisotope and indocyanine green (ICG) with sentinel basins detected using gamma-probe; 2) endoscopic injection of ICG, with sentinel basins detected using a fluorescence imaging system. Standard laparoscopic gastrectomy with lymphadenectomy will be performed. Sample size is calculated based on the inferior confidence interval of the detection rate of 95%, and the calculated accrual is 237 patients. The primary endpoint is detection rate, and the secondary endpoints are sensitivity and postoperative complications.ConclusionsThis study is expected to clarify the feasibility of laparoscopic sentinel basin dissection after noncurative ESD. If the feasibility is demonstrated, a multicenter phase III trial will be initiated to compare laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy in early gastric cancer after endoscopic resection.Trial RegistrationClinicalTrials.gov Identifier: NCT03123042

Long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection for gastric cancer in elderly patients aged ≥ 75years.

Little is known about the long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer. Clinicopathological findings and long-term outcomes were evaluated in 87 patients with early gastric cancer (EGC) aged ≥ 75years who were treated with non-curative ESD. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. During the follow-up period, among 27 patients who died of any cause, only one patient died of gastric cancer. OS probabilities after 3 and 5years were 89.7% and 79.3%, respectively. Univariate analyses revealed that Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index (CCI) ≥ 3, neutrophil/lymphocyte ratio ≥ 3.3, prognostic nutritional index < 44.8, distal tumor location and macroscopically depressed or flat configuration were associated with poor OS. Cox multivariate analysis revealed high CCI (≥ 3) to be an independent prognostic factor associated with OS (hazard ratio: 2.63, 95% confidence interval [CI] 1.06-6.49, P = 0.037). CCI may be a useful parameter for decision-making regarding additional surgery for elderly patients with gastric cancer treated by non-curative ESD.

Propensity score-matched comparison of short-term and long-term outcomes between endoscopic submucosal dissection and surgery for treatment of early gastric cancer in a Western setting.

Endoscopic submucosal dissection (ESD) is a standard treatment option for early gastric cancer (EGC) in Asia; however, data about ESD efficacy in Western populations are limited. Furthermore, outcomes of EGC treatment after ESD or surgery have not been compared in Western cohorts. This study aimed to compare short-term and long-term results of ESD and surgery for EGC. This retrospective case-control study included patients with EGC treated in two largest cancer centers in Eastern Lithuania between 2005 and 2016. Propensity score nearest-neighbor 1:1 matching, based on clinicopathologic characteristics, was performed between patients who underwent ESD and surgery. The primary endpoint of the study was 5-year disease-free survival (DFS). Of 260 eligible patients, 42 (16.1%) underwent ESD. After matching, two well-balanced groups consisting of 42 patients in each were analyzed. The operation time (83 vs. 151min., p = 0.001) and postoperative hospitalization stay (5.4 vs. 13.4 days, p = 0.001) was significantly shorter in the ESD group. 5-year DFS rate was significantly higher in the surgery group (97.6% vs. 77.5%, p = 0.002). However, this difference was reduced after exclusion of non-curative ESD cases (97.6% vs. 89.7%, p = 0.099). There was no significant difference in 5-year OS rate between the study groups (73.8% vs. 69.0%, p = 0.599). ESD might be an excellent alternative to surgery for EGC if curative resection is achieved. Non-curative ESD is associated with poor DFS and high rate of recurrence. Additional surgery should be recommended after non-curative ESD whenever treatment-associated risk is acceptable.

Recurrence Patterns and Outcomes of Salvage Surgery in Cases of Non-Curative Endoscopic Submucosal Dissection without Additional Radical Surgery for Early Gastric Cancer

Background/Aims: The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study. Methods: Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients. Results: Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively. Conclusion: The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases.

Different risk factors between early and late cancer recurrences in patients without additional surgery after noncurative endoscopic submucosal dissection for early gastric cancer

Cancer recurrence is observed in some patients without additional radical surgery after endoscopic submucosal dissection (ESD) that does not fulfill the curability criteria for early gastric cancer (EGC), categorized as "noncurative resection" or "curability C-2" in the guidelines. However, time to cancer recurrence is different in such patients. Thus, we aimed to identify the risk factors of early and late cancer recurrences in these patients. Between 2000 and 2011, this multicenter study analyzed 905 patients who were followed up without additional radical surgery after ESD for EGC categorized as curability C-2. We evaluated the risk factors for early and late cancer recurrences, separately, after ESD. The cut-off value was defined at 2 years. Time to cancer recurrence in the enrolled patients showed a bimodal pattern, and the 5-year cancer recurrence rate was 3.2%. Multivariate Cox analyses revealed that lymphatic invasion (hazard ratio [HR], 8.56; P= .003) was the sole independent risk factor for early cancer recurrence. Regarding late cancer recurrence, vascular invasion (HR, 4.50; P= .039) was an independent risk factor, and lymphatic invasion tended to be a risk factor (HR, 3.63; P= .069). This multicenter study with a large cohort demonstrated that lymphatic invasion is mainly associated with early cancer recurrence; however, vascular invasion was a risk factor only for late recurrence in patients without additional treatment after ESD for EGC categorized as curability C-2. This finding may contribute to decision making for treatment strategies after ESD, especially for patients with a relatively short life expectancy.

Preprocedural prediction of non-curative endoscopic submucosal dissection for early gastric cancer.

Background and aimEndoscopic submucosal dissection (ESD) has been accepted as the treatment of choice for early gastric cancer (EGC) without lymph node metastasis. However, additional surgical gastrectomy should be considered after non-curative endoscopic resection. We aimed to evaluate the predictive factors associated with non-curative endoscopic resection.MethodsBetween November 2008 and June 2015, a retrospective study was conducted in a single, tertiary, referral hospital. A total of 596 EGC lesions resected by ESD were analyzed. Non-curative endoscopic resection was defined as the occurrence of lesions associated with piecemeal resection, positive resection margins, lymphovascular invasion, or lesions that did not meet the expanded indications for ESD.ResultsThe rate of non-curative endoscopic resection was 16.1%. The mean follow-up period was 35.3 ± 25.0 months. Associated predictive factors for non-curative endoscopic resection were female sex (OR, 2.470; p = 0.004), lesion size ≥ 20 mm (OR 3.714; p < 0.001), longer procedure time (OR 2.449, p = 0.002), ulceration (OR 3.538, p = 0.002), nodularity (OR 2.967, p<0.001), depression (OR 1.806, p = 0.038), undifferentiated carcinoma (OR 2.825, p = 0.031) and lesion located in the mid or upper third of stomach (OR 7.135 and OR 4.155, p<0.001, respectively). As the number of risk factors increased, the risk of non-curative ESD also increased.ConclusionsPrior to selection of ESD, the risks associated with non-curative ESD should be considered so that appropriate treatment modalities may be selected.

The eCura system as a novel indicator for the necessity of salvage surgery after non-curative ESD for gastric cancer: A case-control study.

Endoscopic submucosal dissection (ESD) for early gastric cancer does not always lead to complete cancer resection. The aim of this study was to determine indicators for cancer residue (CR) status in cases of non-curative ESD. We analyzed 47 cases of non-curative ESD followed by salvage surgery and collected data regarding the rates of CR, which included both local CR and lymph node metastasis (LNM). To elucidate the risk factors for CR status, we compared the CR positive and the CR negative groups among surgical specimens according to the following variables obtained from ESD findings: tumor location, tumor size, depth of invasion, lympho-vascular invasion, histological margin, and histological diagnosis. The eCura system, which is an LNM risk scoring system, was also applied and scores were calculated in each case as follows: 3 points for lymphatic invasion and 1 point each for tumor size >30 mm, positive vertical margin, venous invasion, and submucosal invasion ≥500 μm. There were 9 (19%) CR positive cases, which included 6 cases of local CR and 4 cases of LNM; no cancer was detected in over 80% of the patients. The eCura scoring system was the only significant factor for CR status: the higher the eCura score, the greater the CR positivity (p = 0.0128). In particular, all patients in the low-risk group (score = 0–1 point) had no CR. Although no cancer recurrence was observed during a median follow-up of 4 years, 2 patients died of pneumonia. In conclusion, the eCura system might make it possible to select appropriate cases for salvage surgery.

Significance of Additional Gastrectomy Including Endoscopic Submucosal Dissection Scar for Gastric Cancer.

The aim of the study was to evaluate the necessity of gastrectomy including endoscopic submucosal dissection (ESD) scar with margin-negative early gastric cancer (EGC). We analyzed 83 patients with EGC who received additional gastrectomy after non-curative ESD and evaluated the risk factors for residual cancer (RC) and lymph node (LN) metastasis. In addition to positive ESD margin, ulceration was a risk factor for RC. Among cases with deep submucosal invasion (sm), 3 were diagnosed as having negative margins in ESD specimens, but the surgical specimens were positive for cancer. The rate of LN metastasis was 12.0%. There was no significant difference in LN metastasis between tumor characteristics. LN dissection is recommended after non-curative ESD. Gastrectomy including the ESD scar should be performed not only for cases with positive margin in ESD, but also for cases with invasion deeper than sm2, even though the margin is negative.

Real-life evaluation of the safety, efficacy and therapeutic outcomes of endoscopic submucosal dissection in a Western tertiary centre.

Endoscopic submucosal dissection (ESD) enables accurate pathological evaluation and low recurrence rates. Large series describing ESD outcomes in Western countries are scarce. To evaluate the real-life experience of ESD in a single Western centre. Data of all the patients submitted to ESD in our centre were prospectively recorded in a database, from the first procedure in 2011 until May 2017. Feasibility, en bloc and R0 resection rates and safety were assessed. Three hundred and one ESDs were performed (37 in submucosal lesions) on 283 patients (54% male). Lesions were located in the oesophagus (n = 13), stomach (n = 169), duodenum (n = 4), colon (n = 35) and rectum (n = 80). ESD was technically successful in 292 lesions (97%); among malignant or premalignant epithelial lesions (n = 232), the en bloc resection rate was 91% and, of those, the R0 resection rate was 87% (between 69% in the colon and 93% in the stomach). Two patients needed surgery due to adverse events. Surgery for non-curative ESD was performed in 12 cases (58% without residual lesion). There were 10 perforations, 9 of them closed endoscopically. Mortality was 0%. Our real-life experience shows that ESD is feasible, safe and effective in Western settings.

Sa1653 - Should Elderly Patients Undergo Additional Treatments after Noncurative Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma? a Multicenter Retrospective Study

Sa1653 - Should Elderly Patients Undergo Additional Treatments after Noncurative Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma? a Multicenter Retrospective Study

A comparison of the clinical outcomes of esophagectomy and chemoradiotherapy after noncurative endoscopic submucosal dissection for esophageal squamous cell carcinoma

PurposeEndoscopic submucosal dissection (ESD) is widely used to treat esophageal cancer, but some patients require additional treatment due to the possibility of lymph node metastasis. The aim of this study was to elucidate the clinical outcomes of these additional treatments.MethodsThe study included 59 patients who developed superficial esophageal squamous cell carcinoma after noncurative ESD treated between 2005 and 2016, of whom 28 underwent esophagectomy and 31 received chemoradiotherapy (CRT).ResultsThe median follow-up periods were 45 months in the esophagectomy group and 41 months in the CRT group. The overall survival did not differ significantly between the groups (P = 0.46). However, there were no recurrences in the esophagectomy group, and the disease-specific survival rate was significantly higher in this group (P = 0.042). Among the patients at high risk for recurrence due to massive tumor invasion (≥ SM2) with lymphovascular invasion (esophagectomy group, six patients; CRT group, ten patients), none in the esophagectomy group had recurrence, whereas four in the CRT group died of esophageal cancer (P = 0.031).ConclusionThe overall survival did not differ significantly between the groups. However, compared with CRT, esophagectomy provided more favorable disease control for patients with massive tumor invasion (≥ SM2) with lymphovascular invasion.

Efficacy and safety of additional surgery after non-curative endoscopic submucosal dissection for early colorectal cancer

BackgroundAdditional surgery is recommended when early colorectal cancer (ECRC) is resected by non-curative endoscopic submucosal dissection (ESD) and there is significant risk of lymph node metastasis (LNM). The aim of this study was to investigate the efficacy and safety of additional surgery after non-curative ESD for ECRC and evaluate long-term outcomes.MethodsPatients with ECRC who underwent ESD and additional surgery between July 2007 and November 2013 were identified. Histology and patient data were collected during an average period of more than 5 years to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis.ResultsFifty-one patients who underwent additional surgery were eligible for analysis. Overall, regional LNM was detected in 5 patients (9.8%) and presence of lymphovascular infiltration was a significant risk factor. Surgery-related complications occurred in 3 patients (5.9%). During a median follow-up period of 59 months, no metastasis or local recurrence was observed. Three patients died of other diseases and no CRC-related deaths took place.ConclusionsAdditional surgery after non-curative ESD for ECRC is effective and safe and should be encouraged to foster curative treatment and better long-term outcomes.

Surgical management for early stage gastric cancer

In the last decade the implementation of the new technique of endoscopic submucosal dissection (ESD) and the rapid progression of laparoscopic gastric cancer (LAG) resection with an adequate lymphadenectomy (LAD) have played an increasing role in the treatment of patients with early stage gastric cancer (EGC). A systematic review of the currently available data in the literature was carried out to evaluate the contemporary surgical management for treatment of EGC. Endoscopic resection (ER) of mucosal T1 gastric cancer (T1m) in accordance with the German guidelines on resection criteria is awidely accepted treatment option, if adefinitive R0 resection can be achieved. Excellent en bloc and R0 results in more than 90% of these cases have been shown particularly for ESD. In contrast to T1m gastric carcinomas with a low risk of lymph node metastases (approximately 3%), nodal involvement reaches more than 20% for submucosal infiltrated EGC (T1sm). For this reason, asurgical resection with adequate LAD is further recommended in all cases of non-curative ER or any T1sm gastric cancer. In seven randomized controlled trials and aseries of meta-analyses including high-quality non-randomized trials, significant benefits in short-term postoperative outcome have been demonstrated for LAG in comparison to open gastrectomy (OG) in the treatment of EGC. The general morbidity was also significantly lower in LAG than in OG. The 30-day mortality and long-term survival outcome were comparable between the two groups. The use of ESD should be the standard treatment for T1m EGC within the guidelines criteria. For non-curative ESD and T1sm gastric cancer, surgical resection with LAD is recommended. The LAG is atechnically safe, feasible, and favorable approach in terms of faster recovery compared to OG. The long-term survival outcome is comparable between LAG and OG for EGC.

Long-term outcomes after noncurative endoscopic resection of early gastric cancer: the optimal time for additional endoscopic treatment

We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD. Of 2527 patients who underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection were reviewed. Noncurative resection is defined as positive resected margins on histology, lymphovascular infiltration, or beyond the expanded criteria for ESD. The mean ± standard deviation follow-up duration was 79.0 ± 55.7 months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery and endoscopic treatment after noncurative resection, respectively, whereas 198 patients (38.7%) were observed. Cancer-specific survival and disease-free survival rates were significantly different among the surgery, other endoscopic treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P=.030; and 92.5%, 73.6%, and 63.0%, respectively; P< .001). When patients who underwent surgery were excluded, the disease-free survival rate of recurrence was not significantly different between the endoscopic treatment and observation groups (73.6% vs 63.0%; P= .548). To exclude the potential for the presence of lymph node metastasis, we further analyzed disease-free survival of local recurrence by comparing the patients with only a positive lateral resection margin. The disease-free survival rate was higher in the endoscopic treatment group than in the observation group (89.2% vs 69.1%; P= .023). Moreover, additional endoscopic treatment within 3 months showed significant associations with lower risk of local recurrence on multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.260; P= .003). In patients with noncurative ESD, additional surgery showed a better long-term outcome; moreover, when a positive lateral resection margin was the only noncurative factor, additional endoscopic treatment within 3 months could be considered to improve disease-free survival.

Survival Benefit of Additional Surgery After Non-curative Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score Matching Analysis.

Previous studies comparing survival outcomes between patients who did and did not undergo additional surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) were limited in that the baseline characteristics differed significantly between the groups. We aimed to address this limitation and compared survival outcomes between these two groups using propensity score matching analysis. The study enrolled 1969 consecutive patients who underwent non-curative ESD for EGC between 2000 and 2011 at any of 19 institutions across Japan. Using propensity score matching analysis, patients who underwent additional surgery (n=1064) were compared with patients who did not (n=905). Overall survival (OS) and disease-specific survival (DSS) after ESD were compared between both groups. Propensity score matching analysis yielded 553 matched pairs and well-balanced baseline characteristics between the two groups. The 5-year OS rates were 91.0% in the additional surgery group and 75.5% in the no additional surgery group, and the 5-year DSS rates were 99.0 and 96.8%, respectively. OS and DSS in the additional surgery group were significantly higher than in the no additional surgery group (OS, p<0.001; DSS, p=0.013). In Cox proportional hazard analysis, additional surgery significantly reduced gastric cancer-related death after non-curative ESD for EGC (hazard ratio 0.33, 95% confidence interval 0.12-0.79, p=0.012). Our findings suggest that additional surgery reduces mortality after non-curative ESD for EGC. We recommend additional surgery for patients after non-curative ESD for EGC.

Long-term oncological outcomes of submucosal manipulation during non-curative endoscopic submucosal dissection for submucosal invasive gastric cancer: a multicenter retrospective study in Japan

Sufficient information is not available on the extent to which lymph node metastasis (LNM) and prognosis are affected by submucosal manipulation during endoscopic submucosal dissection (ESD) for submucosal invasive gastric cancer (SMGC). We aimed to identify the effects of submucosal manipulation during ESD on LNM and prognosis in patients with SMGC. From 19 institutions in Japan, 2526 patients who failed to meet the current curative criteria for ESD between 2000 and 2011 were recruited. After exclusion, 1969 patients were remained. Based on the treatment strategy after ESD, 1064 patients underwent additional radical surgery. A total of 890 of 1064 patients with SMGC, LNM and cancer recurrence, and prognosis were retrospectively reviewed. The median follow-up duration was 67months. A total of 214 patients had SM1 (depth of tumor invasion from the muscularis mucosae <500μm) invasive cancer and 676 patients had SM2 (depth of tumor invasion from the muscularis mucosae ≥500μm) invasive cancer. LNM was found in 84 patients (9.4%), and 14 patients (1.6%) developed cancer recurrence. The 3-year and 5-year overall survival rates were 96.1 and 91.7%, respectively. The 3-year and 5-year disease-specific survival rates were 99.3 and 98.5%, respectively. The rates of LNM and cancer recurrence, and prognosis of patients who underwent additional radical surgery after non-curative ESD for SMGC were excellent. Submucosal manipulation during ESD for SMGC does not seem to enhance the risk for LNM or worsen the prognosis compared to surgical series.

Management of non-curative endoscopic submucosal dissection for early gastric cancer: do we have enough data to support this?

Gastric cancer is one of the most common cancers. Early gastric cancer (EGC) detection is critical for its curative or even non-curative treatment. Gotoda et al . provided important information on the risks of lymph node metastasis (LNM) in a large EGC series (1). Based on their analyses, the expanded criteria for the endoscopic resection of EGC was proposed as follows mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings less than 3 cm in diameter; and minute (<500 μm from the muscularis mucosae) submucosal invasive cancer less than 3 cm in size due to their nominal risks of LNM. Endoscopic submucosal dissection (ESD) has been developed worldwide as an endoluminal therapeutic technique for EGC (2). ESD allows precise histological assessment of the resected one-piece specimens in order to guide further management and to stratify a patient’s risk for developing metastasis including LNM. The long-term outcome of curative EGC patients treated by ESD can be excellent; our previous study showed for the first time that the 5-year overall survival (OS) and disease specific survival (DSS) rates of EGC patients treated by ESD were 97.1% and 100%, respectively (3).

Effect of surgery in patients after non-curative endoscopic submucosal dissection

Over the past decade, endoscopic submucosal dissection (ESD) has emerged as the preferred treatment for patients with early gastric cancer (EGC) without lymph node metastasis (LNM).

Effect of surgery in patients after non-curative endoscopic submucosal dissection

Effect of surgery in patients after non-curative endoscopic submucosal dissection