Complete Endoscopic Submucosal Dissection Research Articles

Adjuvant Radiotherapy is Safe and Effective for Patients with T1b-SM2 Esophageal Carcinoma After Endoscopic Resection – A Second Analysis From a Pilot Study

Radiotherapy or Surgery is recommended for patients with T1b esophageal carcinoma (EC) after endoscopic resection (ER). T1b lesions invading the submucosa to a depth of more than 200 μm (SM2) possess higher metastatic risks. But few studies reported results of radiotherapy for this cohort. Herein, we evaluated the safety and efficacy of adjuvant radiotherapy for T1b-SM2 EC after ER.This study was a second analysis based on a piolet study where adjuvant IMRT (50-60 Gy in 25-30 fractions) with or without chemotherapy was carried out, from July 2011 to April 2019, for 31 stage-T1 EC patients with high risk factors including submucosal or lymphovascular invasion based on endoscopically resected specimen. Of the 31 subjects, patients with T1b-SM2 disease were included in the present study. The common acute toxicities, dysphagia at last follow-up, local control rate (LCR), failure pattern, overall survival (OS) and disease-free survival (DFS) were analyzed.Twenty-four out of the 31 patients were included. There were 19 (79.2%) males and 5 (20.8%) females. The median age was 62.0 (49.0-78.0) years old. Twenty-three (95.8%) patients were squamous cell carcinoma, and one (4.2%) was adenosquamous carcinoma. The number of patients with tumor of high, moderate, moderate-poor and poor differentiation were 2 (8.0%), 12 (48.0%), 3 (12.0%) and 8 (32.0%), respectively. Ten (41.7%) patients were diagnosed with lymphovascular invasion. The median invasion depth was 675.0 (230.0-1550.0) μm. After complete endoscopic submucosal dissection, all patients finished adjuvant radiotherapy as schedule, except one received 44 Gy due to refusal. Five patients (20.8%) received chemotherapy concurrently with radiotherapy. The common acute toxicities included esophagitis (Grade 1-2, 66.7%; Grade 3, 16.7%), radiation pneumonitis (Grade 1, 50.0%), leucopenia (Grade 1-2, 50.0%), and thrombocytopenia (Grade 1-2, 8.3%). No Grade 4-5 acute toxicities were observed. The median follow-up time was 35.5 (95% CI, 27.6-43.3) months. At the last follow-up, 20 (83.3%) patients were able to eat regular diet and only one (4.2%) needed liquid diet. The LCR was 100.0%. Relapse was found in two patients (8.3%), who were all synchronously with distant metastasis and regional lymph node recurrence. The invasion depth was 1300μm and 1400 μm, respectively. The two patients both received radiotherapy alone without chemotherapy. The 1-, 3- and 5-year OS were 100.0%, 87.4%, and 75.0%, respectively. And the 1-, 3- and 5-year DFS were 100.0%, 90.2% and 77.3%, respectively. The median OS and DFS were not reached. No independent prognostic factor was found for OS and DFS.Adjuvant radiotherapy is a safe and efficient supplement treatment for patients with T1b-SM2 EC after ER. For patients with ultra-deep invasion depth, adjuvant chemoradiotherapy or more aggressive treatment may be more reasonable.

Molecular risk markers related to local tumor recurrence at histological margin-free endoscopically resected early gastric cancers: A pilot study

Local recurrences in early gastric cancers (EGCs) after complete endoscopic submucosal dissection (ESD) remain problematic. Here, we investigated the spatially sequential molecular changes in various cancer-related proteins along the axis of the histologically clear but recurrent resection margins (TRM) to determine the appropriate tumor-free margin distance and potential molecular risk markers related to local recurrence. Five eligible patients with recurrent EGCs after complete ESD were selected from 548 EGC patients. The specimens, including recurrent resection margin axis, were divided into 5 zones. Digital spatial profiling assay was performed to quantify the expression level of 31 cancer-related proteins along each zone. p-Chk1 level was significantly reduced in TRM zone than non-recurrent resection margin. The expression of p44/42 ERK and p-Chk1 were significantly decreased along the lateral axis of the recurrent resection margin, with no significance toward the normal zone, which may suggest that p44/42 ERK and p-Chk1 may be involved in the recurrent side compared to non-recurrent margin. Although we could not evaluate more than 5.5 mm, the significant linear decreases in p44/42 ERK and p-Chk1 were maintained until at least 5.5 mm from the tumor zone in the TRM direction. We estimated the possible margin distance using scatterplots and linear regression analyses, which also showed the estimated distance more than 5.5 mm. In conclusion, the p-Chk1 and p44/42 ERK may be potential candidates of molecular risk markers that may be related to the local recurrence after complete ESD, and a tumor-free distance of 5.5 mm is not enough for safety margin.

Analysis of the Pathological Examination Results of 100 Colon Polyps Cases after EMR or ESD Operation

Aim: To study the characteristics of EMR (endoscopic mucosal resection) or ESD (endoscopic submucosal dissection) postoperative pathological examination of colonic polyps in different age groups, and the difference of pathological examination after EMR or ESD operation. Methods: A retrospective analysis was made of the EMR or ESD postoperative pathological data of 100 cases of colonic polyps patients in the Jingzhou Central Hospital digestive internal medicine. The time is from March 2016 to March 2018. Results: In 100 cases of EMR or ESD operation, there are 65 cases of young and middle-aged group. Pathological examination results include: 34 cases of adenomatous polyp, 18 cases of inflammatory polyp, 11 cases of benign tumors, 1 case of malignant tumor, 1 case of hyperplastic polyp. There are 35 cases of elderly group. Pathological examination results include: 27 cases of adenomatous polyp, 2 cases of inflammatory polyp, 2 cases of benign tumors, 4 cases of malignant tumor. 71 cases of complete EMR operation include: 51 cases of adenomatous polyp, 17 cases of inflammatory polyp, 3 cases of benign tumors; 29 cases of complete ESD operation include: 10 cases of adenomatous polyp, 3 cases of inflammatory polyp, 10 cases of benign tumors, 5 cases of malignant tumor, 1 case of hyperplastic polyp. Conclusion: For the pathological examination results after EMR or ESD operation, the proportion of inflammatory polyps in the young and middle-aged group was greater than that in the elderly group. The proportion of adenomatous polyps in the elderly group was larger than that in the young and middle-aged group. The proportion of adenomatous polyps in EMR was greater than that of ESD. The proportion of benign tumors and malignant tumors in ESD was greater than that of EMR. The difference has statistical significance.

Factors associated with incomplete gastric endoscopic submucosal dissection due to misdiagnosis.

Background and study aims: Endoscopic submucosal dissection (ESD) is widely accepted for treating early gastric cancer (EGC); however, there can be cases of incomplete resection due to not only technical problems, but also misdiagnosis. Our aim was to identify factors associated with incomplete gastric ESD due to misdiagnosis. Patients and methods: A total of 2,268 patients with solitary EGCs at initial onset underwent ESD with curative intent at our hospital from 1999 to 2008. We retrospectively assessed the clinicopathological factors by comparing the two groups of incomplete ESD cases due to misdiagnosis (cases with a positive lateral margins [LM] [Group A] or those with a positive vertical margins [VM] [Group B]) with complete ESD cases using multivariable analysis. Results: Complete ESD was achieved in 2,097 patients. The 171 patients with incomplete ESDs were divided into 109 with a positive LM and 80 with a positive VM (overlapped). Except 49 cases with a positive LM due to technical problems, a positive LM due to misdiagnosis was identified in 60 cases (Group A). Excluding 32 cases with a positive VM due to technical problems, a positive VM due to misdiagnosis was found in 48 cases (Group B). Significant independent factors (odds ratios [OR]; 95 % confidence intervals [CI]) for each group were as follows: Group A: size > 20 mm (5.4; 3.0 – 9.9), undifferentiated-type (4.1; 1.8 – 9.0), submucosal invasion (2.0; 1.1 – 3.4) and location of upper/middle (1.9; 1.0 – 3.6); Group B: size > 20 mm (3.0; 1.6 – 5.5), undifferentiated-type (3.0; 1.1 – 8.0) and location of upper/middle (2.4; 1.2 – 4.8). Conclusions: Endoscopists must be aware of these factors associated with incomplete gastric ESD due to misdiagnosis to further decrease their incidence.

The superficial elevated and depressed lesion type is an independent factor associated with non-curative endoscopic submucosal dissection for early gastric cancer.

The expanded criteria for endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) have led to an increase in the number of EGC patients who receive curative treatment involving endoscopic techniques. Identifying the factors that are associated with treatment outcomes would be helpful in the application of ESD for EGC. Potential factors associated with incomplete ESD and with non-curative ESD were investigated using a multiple logistic regression model in EGC patients who consecutively underwent ESD according to the expanded criteria. A total of 363 patients with 398 EGC lesions were enrolled. The rates of complete ESD and curative ESD were 96.2% (383/398) and 85.7% (341/398), respectively. No significant factors associated with incomplete ESD were identified. In contrast, a tumor size >20mm [odds ratio (OR) 3.31; 95% confidence interval (CI) 1.74-6.29], the superficial elevated and depressed type (0-IIa+IIc or IIc+IIa) (OR 4.37; 95% CI 1.88-9.88), and the undifferentiated type (OR 5.93; 95% CI 1.65-19.41) were identified as independent factors associated with non-curative ESD. The superficial elevated and depressed type in particular was found to be highly related to submucosal and lymphovascular invasion. The rate of non-curative ESD in cases of this macroscopic type occurring together with a tumor size >20mm was 58.3%, and the adjusted OR was 16.48 (95% CI 4.69-62.09). The results suggest that the superficial elevated and depressed type is an independent factor associated with non-curative ESD and that the risk of non-curative ESD is increased when this macroscopic type is present along with a large tumor size.

Enhancing proficiency in performing endoscopic submucosal dissection (ESD) by using a prototype robotic endoscope.

Background and study aims: One of the challenges in performing endoscopic submucosal dissection (ESD) is the lack of counter traction during submucosal dissection. MASTER (Master and Slave Transluminal Endoscopic Robot) was designed to allow performance of complex endoluminal procedures using two arms with excellent control. This study aimed to compare the performance of ESD between endoscopists and novices using MASTER. Methods: This is a prospective study comparing the differences in performing ESD using MASTER in an ex vivo porcine stomach model among individuals with or without experience in surgery and endoscopy. Multiple standardized lesions of 20 mm2 were pre-marked on an ex vivo porcine stomach. Each participant received basic training in controlling MASTER before the ESD procedure. The operative time and size of specimen obtained by each participant were noted. Results: Nine individuals (three ESD expert endoscopists, three ESD non-expert endoscopists, and three non-clinician novices) participated in the experiment. All participants completed the ESD procedure for en bloc resection of standardized lesions using EndoMASTER without perforation. The mean times (mean ± SD) taken by ESD expert endoscopists, ESD non-expert endoscopists, and novices to complete Robotic ESD were 122 ± 58 s, 203 ± 150 s, and 561 ± 496 s, respectively. There was no statistically significant difference in the mean operative time to complete the ESD between the three groups (P = 0.242). When the performance of the six endoscopists was compared to that of the three novices, the endoscopists took an average of 162 ± 111 s to complete the ESD, while the non-clinicians required an average of 561 ± 496 s (P = 0.085). Conclusions: There was a trend to shorter operative time when comparing endoscopists to non-endoscopists in performing ESD using MASTER. The use of MASTER enabled the novice without endoscopy experience to complete the ESD procedure.

Updates on endoscopic therapy of esophageal carcinoma.

Endoscopic submucosal dissection (ESD) has the advantage over endoscopic mucosa resection (EMR), permitting removal of gastrointestinal neoplasms en bloc, but is associated with a relatively high risk of complications. Early esophageal cancer (EEC) is indicated when the tumors are confined to the two-third layer of the lamina propria. Esophageal stricture following semicircular or complete circular esophageal ESD is relatively frequent even if treated by multiple pre-emptive endoscopic balloon dilatation. Oral prednisolone may offer a novel, safe, and effective option for prevention of post-ESD stricture associated with ESD for extensive esophageal neoplasms. The procedures include marking, submucosal injection, circumferential mucosal incision and exfoliation of the lesion along the submucosal layer. Complete ESD can achieve a large one-piece resection, allowing precise histological assessment to prevent recurrence. Clinical outcomes of esophageal ESD have been promising, and the prognosis of EEC patients treated by ESD is likely to be excellent, though further long-term follow-up studies are warranted. Notification of a risk of perforation is essential for esophageal ESD. Bleeding during ESD can be managed with coagulation forceps, and postoperative bleeding may be reduced with routine use of the stronger acid suppressant, proton pump inhibitors.

Procedure time of endoscopic submucosal dissection according to the size and location of early gastric cancers: analysis of 916 dissections performed by 4 experts

Endoscopic submucosal dissection (ESD) is curative treatment for patients with early gastric cancer (EGC). Because of the technical difficulties, however, these procedures may take a long time, which can increase the rate of procedure-related complications. To investigate the procedure time of ESD performed by 4 experts according to the location and size of the EGC. Retrospectively analyzed study of prospectively collected data. Tertiary care, academic medical center. Complete ESDs were performed by 4 experts, primarily using an insulated-tip knife, for 916 EGCs. ESD. Procedure time relative to the location and size of tumors was analyzed along with other predictive factors. ESD procedure time was increased as tumor size increased and for tumors in the middle and lower thirds of the stomach. Univariate analysis showed that tumor size, location, depth, submucosal fibrosis, and perforation during the procedure were significant predictors of procedure time. Multivariate analysis showed that proximal location, tumor size greater than 20 mm, submucosal fibrosis, and perforation during the procedure were independent predictors of a longer procedure time. Single-center, retrospective study design. Procedure time became longer as tumor location became higher and as tumor size increased, except for tumors in the upper third of the stomach. These findings suggest that tumor size and location may be useful in predicting the time required to perform ESD.

Endoscopic Submucosal Dissection in the Era of Proton Pump Inhibitors

Endoscopic submucosal dissection (ESD) has the advantage over endoscopic mucosa resection, permitting removal of gastrointestinal neoplasms en bloc, but is associated with relatively high risk of complications. Indications for early gastric cancer (EGC) are expanded: mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings ≤3 cm in diameter; and minute submucosal invasive cancer ≤3 cm in size. The indications for early esophageal cancer (EEC) are the tumors confined to the two-third layer of the lamina propria. The EEC lesions spreading more than three-quarter of circumference of the esophagus are at frequent risk of stenosis. The procedures include marking, submucosal injection, circumferential mucosal incision and exforiation of the lesion along the submucosal layer. Complete ESD can achieve a large one-piece resection, allowing precise histological assessment to prevent recurrence. Clinical outcomes of gastric and esophageal ESD have been promising, and the prognosis of EGC patients treated by ESD is likely to be excellent, though further longer follow-up studies are warranted. Notification of perforation risk is essential in particular for esophageal ESD. Bleeding during ESD can be managed with coagulation forceps, and postoperative bleeding may be reduced with routine use of the stronger acid suppressant, proton pump inhibitors.

Degree of Healing and Healing-Associated Factors of Endoscopic Submucosal Dissection-Induced Ulcers After Pantoprazole Therapy for 4 Weeks

There is no consensus regarding the degree of healing of endoscopic submucosal dissection (ESD)-induced ulcers and the optimal duration of proton pump inhibitor (PPI) treatment. To evaluate the degree of healing and the factors associated with healing of ESD-induced ulcers after PPI therapy for 4 weeks. Fifty-six patients who underwent complete ESD for adenoma or early gastric cancer were enrolled. All patients underwent follow-up endoscopy to evaluate the degree of ulcer healing after pantoprazole therapy (40 mg per day) for 4 weeks. We evaluated change in size of ESD-induced ulcers between baseline and 4 weeks, and correlated relevant factors with degree of healing of small and large ulcers. At follow-up, 28 (50%) patients had large ulcers (area > 10 mm(2)). Ulcer size at 4 weeks was closely correlated with initial ulcer size (P < 0.001) and abruptly increased when initial ulcer size was larger than 4 cm. Comorbidity, procedure time, and initial specimen size were significantly associated with healing rate, but multivariate analysis showed that initial ulcer size was the only significant parameter (P < 0.015). Healing degree of ESD-induced ulcers at 4 weeks is dependent on initial ulcer size, indicating that duration of treatment with PPI should be dependent on initial ulcer size.

A novel device for endoscopic submucosal dissection, the Fork knife

To introduce and evaluate the efficacy and technical aspects of endoscopic submucosal dissection (ESD) using a novel device, the Fork knife. From March 2004 to April 2008, ESD was performed on 265 gastric lesions using a Fork knife (Endo FS) (group A) and on 72 gastric lesions using a Flexknife (group B) at a single tertiary referral center. We retrospectively compared the endoscopic characteristics of the tumors, pathological findings, and sizes of the resected specimens. We also compared the en bloc resection rate, complete resection rate, complications, and procedure time between the two groups. The mean size of the resected specimens was 4.27 +/- 1.26 cm in group A and 4.29 +/- 1.48 cm in group B. The en bloc resection rate was 95.8% (254/265 lesions) in group A and 93.1% (67/72) in group B. Complete ESD without tumor cell invasion of the resected margin was obtained in 81.1% (215/265) of group A and in 73.6% (53/72) of group B. The perforation rate was 0.8% (2/265) in group A and 1.4% (1/72) in group B. The mean procedure time was 59.63 +/- 56.12 min in group A and 76.65 +/- 70.75 min in group B (P < 0.05). The Fork knife (Endo FS) is useful for clinical practice and has the advantage of reducing the procedure time.

Clinical Impact of Partial Submucosal Dissection Compared with Complete Submucosal Dissection During Endoscopic Submucosal Dissection for the Treatment of Early Gastric Cancer Or Adenoma

Background/Aims: For complete resection of large gastric mucosal tumors over 2 cm in diameter, endoscopic submucosal dissection (ESD) is reported to be more useful compared with conventional methods such as strip biopsy. However, complete submucosal dissection for removal of tumor in a single fragment necessitate the long procedure time and high complications rate of bleeding or perforation. This long procedure time can be decreased if the tumor is dissected partially until the partially dissected tumor is expected to be easily snared without aid of grasping forcep and removed with electrosurgical snare. The aim of this study was to compare the clinical impact of partial submucosal dissection method with complete submucosal dissection method during ESD for early gastric cancer or gastric adenoma. Methods: During the past 2 years, a total of 186 gastric tumor (EGC, 89; adenoma 97) was resected endoscopically by using ESD techniques. Of these, 56 patient underwent partial submucosal dissection and snare removal (partial ESD group) and 130 patient complete submucosal dissection (complete ESD group). The size of tumor, en bloc and complete resection rate, and complication was assessed and compared. Results: The two groups were similar with respect to age, gender, macroscopic appearance, and the site. The proportion of larger tumor (over 20 mm in longest dimension) was significantly higher in partial ESD group than in complete ESD group (25% vs. 55%) (p < 0.01). The rate of en bloc resection was significantly higher with complete ESD group (93%) than with partial ESD group (81%) (p < 0.05). The rate of complete resection (defined as free lateral and vertical margin, negative lymphatic emboli) was higher with complete ESD group than with partial ESD group, but not statistically significant (91% vs. 88%, p> 0.05). As for complications, the rate of bleeding and perforation in partial and complete ESD was not significantly different (23% vs. 19%, 1.8 vs. 2.2%, respectively). Conclusions: ESD is a useful procedure for en bloc resection of large gastric tumor. For the tumor especially less than 20 mm in size, partial submucosal dissection and snare removal can be a time saving and easier ESD method than through-the procedure complete dissection.