Dissection For Early Gastric Cancer Research Articles

Endoscopic Submucosal Dissection for Early Gastric Cancer using the Clutch Cutter: a large single-center experience.

Background and study aims: The Clutch Cutter (CC) was developed to reduce the risk of complications related to endoscopic submucosal dissection (ESD) using knives. The CC is able to grasp and coagulate and/or incise the targeted tissue using electrosurgical current, like a biopsy technique. The aim of this study was to evaluate the efficacy and safety of ESD using the CC (ESD-CC) for early gastric cancer (EGC). Patients and methods: From June 2007 to March 2014, 325 consecutive patients with a diagnosis of EGC were enrolled in this prospective study. They had all satisfied the Japanese gastric cancer treatment guidelines for ESD indication, namely confirmation by preliminary endoscopy, endoscopic ultrasound, and endoscopic biopsies. The CC was used for all steps of ESD (marking, circumferential marginal incision, submucosal dissection, and hemostatic treatment). The therapeutic efficacy and safety were assessed. Results: The en-bloc resection rate was 99.7 % (324/325) and the R0 resection rate was 95.3 % (310/325). The mean operating time was 97.2 minutes. Perforation during ESD-CC occurred in one case (0.3 %), which was managed with conservative medical treatment after endoscopic closure of the perforation. Post-ESD-CC bleeding occurred in 11 cases (3.4 %), which were successfully treated by endoscopic hemostatic treatment. The R0 resection rate was significantly low in tumors > 20 mm (88.9 %), and in the exclusion indication group (73.7 %). Significant differences were seen in the mean operating time, depending upon tumor size, histologic type, location, and indication criteria. Conclusions: ESD-CC is a technically efficient, safe, and easy method for resecting EGC.

Surveillance strategy based on the incidence and patterns of recurrence after curative endoscopic submucosal dissection for early gastric cancer.

To suggest an appropriate surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancers, based on incidence and patterns of local, metachronous, and extragastric recurrence. Between 2003 and 2011, 1497 consecutive patients with 1539 differentiated-type early gastric cancers meeting absolute or expanded indication criteria underwent curative ESD. They were followed up with esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) under a standardized surveillance protocol. Long-term outcomes were analyzed for 1306 patients with at least 1 year's follow-up. Incidences of residual and synchronous lesions detected within 1 year were 0.13 % and 0.87 %, respectively. During median 47 months of follow-up, there was 1 local recurrence (0.08 %; early gastric cancer) and 47 cases of metachronous recurrence (3.6 %; 44 early gastric cancers, 3 pT2 advanced gastric cancers); all were curatively treated. During a 5-year surveillance, the cumulative incidence curve of metachronous recurrence increased linearly. Median time from ESD to metachronous recurrence was 30 months. There were 2 extragastric recurrences (0.15 %) in lymph nodes, at 5 and 4 years, respectively, after curative ESD for absolute and expanded indications. The patient with the expanded indications underwent a palliative operation and died of gastric cancer progression. There was a constant incidence rate of metachronous recurrence during a 5-year surveillance period and there was extragastric recurrence at least 4 years after ESD of early gastric cancer even for absolute indications. Therefore, annual or biannual surveillance EGD and abdominal CT might be necessary for at least 5 years after curative ESD for early gastric cancers, with absolute as well as expanded indications.

Endoscopic submucosal dissection for early gastric cancer with undifferentiated-type histology: A meta-analysis.

To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with undifferentiated-type histology. A systematic literature review was conducted using the core databases. Complete resection, curative resection, en bloc resection, recurrence and adverse event rate were extracted and analyzed. A random effect model was applied. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated using a funnel plot, the trim and fill method, Egger's test, and a rank correlation test. Fourteen retrospective studies between 2009 and 2014 were identified (972 EGC lesions with undifferentiated-type histology). The total en bloc and complete resection rates were estimated as 92.1% (95%CI: 87.4%-95.2%) and 77.5% (95%CI: 69.3%-84%), respectively. The total curative resection rate was 61.4% (95%CI: 44.5%-75.9%). The overall recurrence rate was 7.6% (95%CI: 3.4%-16%). Limited to histologically diagnosed expanded-criteria lesions, the en bloc and complete resection rates were 91.2% and 85.6%, respectively. The curative resection rate was 79.8%. In this analysis, ESD is a technically feasible treatment modality for EGC with undifferentiated-type histology. Long-term studies are needed to confirm these therapeutic outcomes.

Sa1550 Risk Stratification and Management of Non-Curative Resection After Endoscopic Submucosal Dissection for Early Gastric Cancer

Sa1550 Risk Stratification and Management of Non-Curative Resection After Endoscopic Submucosal Dissection for Early Gastric Cancer

Mo1560 Validity of Endoscopic Submucosal Dissection for Early Gastric Cancer in Super-Elderly Patients With Concomitant Diseases

group performance status (ECOG-PS) was 0 in 3 patients, 1 in 11 patients, 2 in 11 patients and 3 in 3 patients. The main indications for stent placement were pancreatic adenocarcinoma with duodenal infiltration in 13 (46.4%) patients, gastric adenocarcinoma in 7 (25%), cholangiocarcinoma in 3 (10.7%), duodenal adenocarcinoma in 3 (10.7%) and 1 (3.6%) in each of small bowel adenocarcinoma and gall bladder adenocarcinoma. Technical success rate for stent deployment was 100% and oral intake was possible in all (100%) of the stented patients with 93% of patients being capable of eating at least a mechanical soft diet. There were no sedation related adverse events and procedure related complications including perforation and haemorrhage. Among late complications there were 3 (10.7%) stent obstructions related to tumour ingrowth requiring re-insertion of stents and 1 (3.5%) biliary obstruction requiring biliary stent insertion. The mean survival from stent placement to death was 111 days (range 9-438). Three patients (11%) were still alive after an average of 250 days post stent deployment. 30 days mortality was 6 (21%) but this was related to advance malignant disease rather related to endoscopic stent placement. Conclusion: In our experience enteral stenting is a safe palliative procedure and it improves quality of life by relieving gastrointestinal obstruction and restoration of enteral tract for nutrition in all successfully stented cases. Enteral stenting contributed towards an average survival of around four months and hence must be considered in this high risk group of patients.

Mo1561 Clinical Outcome of Absolute Versus Expanded Indication of Endoscopic Submucosal Dissection for Early Gastric Cancer

The treatment of early gastric cancer (EGC) by endoscopic submucosal dissection (ESD) has been rapidly gaining popularity in Korea. Current guidelines for endoscopic management such as EMR and endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) are in evolution, with broader indication criteria.In Korea, indication of ESD for early gastric cancer have been still one of big issue.

211 Long Term Outcomes and Prognosis of Endoscopic Submucosal Dissection for Early Gastric Cancer: a Multi-Institutional Joint Study

The indication for endoscopic submucosal dissection (ESD) in patients with early gastric cancer (EGC) has been expanded. However the long term prognosis in these patients treated with ESD remains unclear. The aim of this study was investigate the long term prognosis in patients who underwent ESD for EGC.

Outcomes of endoscopic submucosal dissection for early gastric cancer and precancer lesion: Experience from a center in Southern Taiwan

SummaryBackgroundLimited data are available on the interval of disease‐free status after endoscopic submucosal dissection (ESD) for early gastric cancer and precancer lesion in Taiwan. In this long‐term (2–105 months) follow‐up study, we analyzed the risk factors that affect the local recurrence and noncurative resection (non‐CR) of these lesions.MethodsWe retrospectively studied 65 consecutive treatment‐naïve patients with 69 EGC lesions who were selected to be treated by ESD. A total of 56 lesions (48 CR lesions and 8 non‐CR lesions) were analyzed for local recurrence after ESD.Results and DiscussionESD was curative for gastric epithelial tumors in 51 (73.9%) but not in 18 (26.1%) lesions. Unfortunately, five (8.93%) of these 56 lesions in 53 patients had local recurrence. None of the patients died from gastric cancer‐associated diseases during follow‐up. In our studies, the cumulative local recurrence rates were 5.3% in the CR group and 56.7% in the non‐CR group (p = 0.0091). The disease‐free status was high (94.7%) with CR. The risk factors that affect the non‐CR were tumor location (p = 0.013), deeper invasion (p < 0.001), undifferentiated histopathology (p < 0.001), and ulcer presence (p = 0.045).ConclusionESD offers good outcome after treatment for EGC. To decrease the risk of local recurrence, preoperative diagnosis of tumor extent and accurate postoperative pathological evaluation are very important.

Risk stratification and management of non-curative resection after endoscopic submucosal dissection for early gastric cancer.

Non-curative resection after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) can contribute to local recurrence or lymphatic and distant metastasis of the tumor. We stratified the risk of local recurrence according to the histological characteristics in non-curative resection after ESD for EGC. Among 892 EGCs treated with ESD, 152 (17.0%) were classified as non-curative resection based on the histology after ESD. The clinical outcomes and risk factors associated with local recurrence were analyzed retrospectively in non-curative resections. Of 152 non-curative resections, 46 (30.3%) were stratified as Group 1 (incomplete resection and met the ESD criteria), 31 (20.4%) as Group 2 (complete resection and exceeded the ESD criteria), 41 (27.0%) as Group 3 (incomplete resection and exceeded the ESD criteria), and 34 (22.4%) as Group 4 (lymphovascular invasion regardless of complete resection). Group 3 [odds ratio (OR) 3.991; p = 0.015] and Group 4 (OR 4.487; p = 0.014) had higher rates of local recurrence after non-curative resection. In those high-risk groups, endoscopic surveillance without additional treatment detected significantly more local recurrence than in those receiving additional treatment (p = 0.029). Risk stratification for non-curative resection is important for EGC prognosis after ESD. Moreover, additional treatment for non-curative resection influences long-term outcomes, especially in high-risk groups.

Su1991 Surveillance Strategy Based on the Incidence and Patterns of Recurrence After Curative Endoscopic Submucosal Dissection for Early Gastric Cancer

BACKGROUND& AIMS: Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Despite improvements in chemotherapy and introduction of molecular targeted therapy, the prognosis of patients with unresectable or metastatic gastric cancer remains poor. Novel approaches for gastric cancer treatment are thus urgently needed. Combinatorial strategy can provide dramatic improvements over monotherapies. Targeting of protein phosphatase 2A (PP2A), a ubiquitous serine/threonine phosphatase with broad substrate specificity, has shown promising efficacy in combination with chemo-therapy and radiotherapy. In this study, we systematically analyzed synergism between LB-100, a PP2A inhibitor, and chemotherapeutic agents in the treatment of gastric cancer.METHODS:The effect of LB-100 on a panel of gastric cancer cell lines was determined by cell viability assay, colony formation assay and the xCELLigence system. The synergism between LB-100 and four chemotherapeutic drugs (Cisplatin, Docetaxel, Doxorubicin and 5-Fluorouracil), as assessed by cell viability and colony formation assays, was determined by isobologram analysis and quantified using the combination index (CI). The effect of monoand combination therapieson cytokinetic parameters, including apoptosis induction and cell cycle arrest, was evaluated. Activation of the apoptosis cascade and alternations in the cell cycle-associated proteins were investigated by western blot. RESULTS: As a single agent, LB-100 inhibited the growth of gastric cancer cells with IC50 values between 0.5 and 10μM. Real time cell viability measurement by using the xCELLigence system showed that LB-100 caused rapid cell death within the first two hours of treatment. Analysis of the synergism between LB-100 and four chemotherapeutic drugs including Cisplatin (DNA damaging agent), Docetaxel (anti-mitotic agent), Doxorubicin (topoisomerase poison) and 5-Fluorouracil (anti-metabolite), revealed that LB-100 potently synergized with Docetaxel (CI: 0.13 to 0.83) and Doxorubicin (CI: 0.32 to 0.66) in inhibiting gastric cancer cell growth. On the other hand, it was ineffective as a sensitizing agent for Cisplatin and 5Fluorouracil (CI>1). For both anticancer drugs (Docetaxel and Doxorubicin), co-treatment with LB-100 significantly enhanced the induction of apoptosis and cell cycle arrest at G2/M phase. These were confirmed by the observations thatthe drug combination treatment induced an increased activation of pro-apoptosis caspase-9-dependent cascade and decreased expression of key cell cycle regulators cyclin D1 and cyclin D3. CONCLUSIONS: Our results demonstrated that LB-100 is a potent sensitizing agent for chemotherapeutic drugs and support further exploration of PP2A inhibition as a novel drug combination regimen with Docetaxel or Doxorubicin in the treatment of gastric cancer.

Adverse events associated with endoscopic dilation for gastric stenosis after endoscopic submucosal dissection for early gastric cancer

Gastric stenosis is a major problem after endoscopic submucosal dissection (ESD) for large early gastric cancer, but little is known about the incidence of adverse events associated with endoscopic dilation (ED) for stenosis caused by gastric ESD. The aims of this study were to determine the incidence and risk of bleeding and perforation associated with ED for gastric stenosis after ESD. This was a single-center, retrospective cohort study conducted at a specialized center for treating cancer. A total of 342 procedures of wire-guided balloon ED were performed for stenosis after gastric ESD in 64 patients. The incidence of adverse events and related clinical characteristics was analyzed. The incidence of bleeding was 3.1% (2/64) per patient and 0.6% (2/342) per procedure. One bleeding case with incomplete cessation of antithrombotics before ED required blood transfusion. The incidence of perforation was 7.8% (5/64) per patient and 1.5% (5/342) per procedure. All perforations occurred in the lower part of the stomach. Two of the five perforation cases were inappropriate for nonoperative therapy, and thus, emergency surgery was performed. Among the other three perforation cases, one case required surgery for refractory stenosis and ED was continued in one case after nonoperative therapy. The incidence of bleeding caused by ED for gastric stenosis after ESD was small. Although not significant, ED in the lower stomach presents a substantial risk of perforation.

Endoscopic Submucosal Dissection of Early Gastric Cancer: Yes, We Need to Calculate Procedure Times!

Endoscopic Submucosal Dissection of Early Gastric Cancer: Yes, We Need to Calculate Procedure Times!

Clinicopathological factors of multiple lateral margin involvement after endoscopic submucosal dissection for early gastric cancer.

In some ESD specimens of EGC, tumors involve multiple lateral margins. However, the factors related to the number of lateral margins involved are unclear. We evaluated the factors related to the multiplicity of lateral margin involvement in specimens of ESD for EGC. The study included 1,358 patients treated with ESD for EGC between March 2004 and September 2011 at a single tertiary hospital. Of those, 71 patients (5.2%) were found to have lateral margin-positive specimens. The demographic, endoscopic, and pathological features between the single lateral margin-positive lesions (SLM+ group) and the multiple lateral margin-positive lesions (MLM+ group) were compared retrospectively. Single lateral margin involvement was noted in 43 lesions (60.6%), and multiple lateral margin involvement was seen in 28 lesions (39.4%). Extremely well-differentiated adenocarcinoma (EWDA) and histological heterogeneity were more common in the MLM+ group (p = 0.043 and p = 0.070, respectively). In multivariate analysis, EWDA was the only significant risk factor for multiple lateral margin involvement (OR 4.453 [1.011-19.624, 95% CI], p = 0.048). Surgery was performed in 65% (46/71) of the patients as an additional treatment for positive lateral margin, while 20% (14/71) of the patients underwent an additional ESD. After additional treatment, residual tumors were observed in 65% (39/60) of the specimens. There was no local recurrence among the patients treated with either type of additional treatment. In ESD for EGC, multiple lateral margin involvement was related to the histological characteristics of the tumor, such as extremely well-differentiated adenocarcinoma and histological heterogeneity.

Outcome of endoscopic submucosal dissection for early gastric cancer of conventional and expanded indications: systematic review and meta-analysis.

Current guidelines for treating early gastric cancer (EGC) with endoscopic submucosal dissection (ESD) are being developed with broader criteria. This systematic review and meta-analysis aimed to assess the application of expanded indications (EIN) by comparing outcomes between conventional indication (CIN) and EIN groups. Literature databases were searched. Short-term outcomes, including endoscopic resection rates, complications and local recurrence, and long-term outcomes including gastric cancer-specific mortality and overall mortality were compared in the two groups. In all, 13 studies were identified and evaluated. The EIN group had lower rates of en bloc (93.6% vs 97.0%, P < 0.0001), complete (87.8% vs 95.8%, P < 0.00001) and curative resection (82.4% vs 94.0%, P < 0.00001) than the CIN group. The rates of delayed bleeding and perforation were both significantly higher in the EIN group (3.9% vs 2.8%, P = 0.04 and 3.9% vs 1.8%, P < 0.0001). Local recurrence rates were 0.6% in the CIN group and 1.5% in the EIN group (P = 0.03). There were no significant differences between the two groups in the gastric-cancer specific mortality (P = 0.22) and the overall mortality (P = 0.37). Long-term mortality in the EIN group did not significantly differ from those in the CIN group, although the EIN group was associated with more unfavorable short-term outcomes. Thus, ESD could be recommended as an effective therapy for EGC of EIN.

Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multicenter large-scale retrospective analysis of short- and long-term outcomes

Objective. The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection. Materials and methods. The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group. Results. Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence. Conclusion. The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

What Is Optimal Timing of Surveillance after Curative Endoscopic Submucosal Dissection for Early Gastric Cancer?

What Is Optimal Timing of Surveillance after Curative Endoscopic Submucosal Dissection for Early Gastric Cancer?

Endoscopic submucosal dissection in early gastric cancer in elderly patients and comorbid conditions

The prognosis of early gastric cancer (EGC) is good if there is no concomitant lymph node metastasis. Therefore, the early detection of EGC is important to improve the prognosis of patients with gastric cancer. In Japan, 40% to 50% of all gastric cancers are EGC, and endoscopic submucosal dissection (ESD) is widely accepted as a local treatment for these lesions, particularly for large lesions that at one time were an indication for gastrectomy because of the difficulty of en-bloc resection. Consequently, this procedure can preserve the entire stomach and the patient's postoperative quality of life. ESD has become a general technique with improved procedures and devices, and has become the preferred treatment for EGC rather than gastrectomy. Therefore, ESD may demonstrate many advantages in patients who have several comorbidities, particularly elderly population, patients taking antithrombotic agents, or patients with chronic kidney disease, or liver cirrhosis. However, it is not yet clear whether patients with both EGC and comorbidities are feasible candidates for ESD and whether they would consequently be able to achieve a survival benefit after ESD. In this review, we discuss the clinical problems of ESD in patients with EGC and those comorbid conditions.

Long-term outcome after endoscopic submucosal dissection for early gastric cancer: focusing on a group beyond the expanded indication.

To determine the long-term outcome after endoscopic submucosal dissection (ESD) in patients with early gastric cancer (EGC) according to the pathological extent. ESD were performed in 280 patients with 309 EGC. The tumors were classified by pathological severity based on absolute indication (AI), expanded indication (EI) or beyond expanded indication (BEI). The therapeutic outcomes among the three groups were analyzed. The complete resection rates of EGC were 96.4%, 78.7% and 41.2% in the AI-EGC, EI-EGC and BEI-EGC groups, respectively (P = 0.000). En bloc resection rates were 97.6%, 87.4% and 86.3% in the AI-EGC, EI-EGC and BEI-EGC groups, respectively (P = 0.023). The 5-year tumor recurrence rates were 1.8%, 1.5% and 15.4% in the AI-EGC, EI-EGC and BEI-EGC groups, respectively (P = 0.000). The 5-year disease-specific survival rates were 100%, 100% and 97.4% in the AI-EGC, EI-GEC and BEI-EGC groups, respectively (P = 0.088). The 5-year disease-free survival rates were 98.2%, 98.5% and 84.6% in the AI-EGC, EI-EGC and BEI-EGC groups, respectively (P = 0.000). ESD was effective and safe in treating AI-EGC and EI-EGC, but there was a comparatively high rate of recurrence after ESD in the BEI-EGC group. However, long-term outcomes of patients with BEI-EGC that did not receive additional surgery were better than those with an natural course of EGC. Thus, ESD may be considered for specific BEI-EGC patients at high risk for surgery.

Perioperative complications of endoscopic submucosal dissection for early gastric cancer in elderly Japanese patients 75 years of age or older.

The number of endoscopic submucosal dissection (ESD) procedures for early gastric cancers among patients 75 years of age or older has been increasing. We herein examined both the outcomes and complications of ESD in elderly patients. We investigated the effects of underlying diseases, lesion characteristics, treatment outcomes and complications during and in the postoperative periods of ESD among elderly patients 75 years of age or older versus non-elderly patients less than 75 years of age. Patients A total of 318 early gastric cancers in consecutive 307 patients, all of whom underwent ESD for gastric cancer, were included in this study. The number of patients with hypertension and ischemic heart disease was significantly higher in the elderly group than in the non-elderly group. The proportion of lesions with an absolute indication, extended indication or no indication was not significantly different between the groups. During the ESD procedure, the use of atropine sulfate for bradycardia was significantly more frequent in the elderly group. No significant differences were observed between the groups in terms of the treatment for hypertension, oxygen administration or incidence of perforation. In addition, there were no significant differences with respect to oxygen administration, postoperative bleeding or the occurrence of fever and/or pneumonia after the ESD procedure. Although bradycardia was more frequently observed in the elderly patients during ESD in this study, ESD was performed safely and managed appropriately, with infrequent postoperative complications. ESD appears to be effective, even in elderly patients.

Delayed Perforation Occurring after Endoscopic Submucosal Dissection for Early Gastric Cancer.

Delayed perforation is a very rare complication of endoscopic submucosal dissection (ESD), with a reported incidence of 0.1% to 0.45%. Few reports exist on the clinical features and outcomes of delayed perforation after ESD, and it is unclear whether the optimal management strategy is emergency surgery or endoscopic closure with conservative treatment. Here, we report two cases of delayed perforation occurring after ESD for early gastric cancer. In both cases, lesions were located in the antrum, and tumor depths were confined to the mucosal layer. Total procedure times for ESD were 25 and 45 minutes, respectively. Because delayed perforation may be associated with excessive thermal damage and necrosis of the muscle layer, treatment with emergency surgery should be used instead of conservative management in cases of delayed perforation after ESD.