A randomized controlled trial of rebamipide plus rabeprazole for the healing of artificial ulcers after endoscopic submucosal dissection

Background  

Endoscopic submucosal dissection (ESD) is an increasingly common technique for the resection of early gastric cancers. Although 8 weeks of treatment with a proton pump inhibitor (PPI) reportedly heals most patients with ESD-derived artificial ulcers, it does not heal those with severe atrophic gastritis, for whom there is little data. This study examined whether healing rates of the latter especially were improved by the addition of the non-PPI mucosal healing agent rebamipide after ESD.     

Single‐center implementation of endoscopic submucosal dissection (ESD) in the colorectum: Low recurrence rate after intention‐to‐treat ESD

Background and Aim

Colorectal endoscopic submucosal dissection (ESD) shows higher R0 resection and lower local recurrence rates than endoscopic mucosal resection (EMR) in Japan. In Europe, independent learning of ESD in the colorectum is feasible, but yet to be analyzed for curative resection and recurrence rates.

Methods

After experimental training under supervision by Japanese experts (T.O., N.Y.), three endoscopists independently carried out 83 ESD procedures intention‐to‐treat for lesions in the entire colorectum of 67 patients in a prospective registry (November 2009 to June 2016).

Results

ESD was feasible in 80 (96%) colorectal neoplasias (mean diameter 33.6 [± 1.8] mm), and three more required conversion to piecemeal EMR. The lesions were adenomas in 66% with low‐grade intraepithelial neoplasia (LGIN), 29% with high‐grade intraepithelial neoplasia, and 5% with carcinomas (G2, pT1). ESD had to be facilitated by the final use of snaring (hybrid‐ESD, n = 45), especially in the initial learning period. En‐bloc resection rate was 85%. Complications were microperforations (7%, conducive to one hemicolectomy), and delayed bleeding (1%) without mortality or long‐term morbidity. Residual adenomas with LGIN (5%) after hybrid‐ESD did not recur after endoscopic ablation. All malignant neoplasias (34%) were curatively resected without recurrence after a mean follow up of 19.5 (± 3.2) months.

Conclusions

During independent ESD learning in the colorectum, ESD intention‐to‐treat showed a low recurrence rate after appropriate training, and hybrid‐ESD showed acceptable complication and recurrence rates, justifying hybrid‐ESD as a strategy for self‐completion and rescue.     

Randomized controlled trial comparing submucosal endoscopy with mucosal resection and endoscopic submucosal dissection in the esophagus and stomach: Animal study

Background and Aim

In Western countries, endoscopic submucosal dissection (ESD) has not prevailed as a result of training problems and a target patient population. We have previously reported a hybrid ESD technique, submucosal endoscopy with mucosal resection (SEMR), in which the submucosal dissection is carried out chiefly by blunt balloon dissection. We have also reported successful application in the porcine colon. In the present study, we compared the safety and efficacy of SEMR with ESD in the porcine esophagus and stomach.

Methods

SEMR and ESD were carried out in eight domestic pigs under general anesthesia. Resection sites were marked by circumferential coagulation. After circumferential ESD knife mucosal incision, submucosal fluid cushion (SFC) was created. In the SEMR group, the balloon catheter was inserted deep into the SFC. The balloon was then inflated and pulled back toward the endoscope tip repeatedly, altering the direction, to disrupt the submucosa. Residual strands were cut with an IT‐knife. En bloc resection rates, procedure times, complications and dissection difficulty scales (DDS) were recorded prospectively. DDS were rated using a visual analog scale.

Results

Thirty‐two resections (8 SEMR/8 ESD in the esophagus; 8 SEMR/8 ESD in the stomach) were done with no major adverse events. There was no statistical difference between the two techniques in either location in the above categories measured.

Conclusions

SEMR and traditional ESD are comparable techniques in safety and effectiveness when carried out in the esophagus and stomach. SEMR may serve as a more appealing technical option for endoscopists who are unable to sustain a traditional ESD practice volume.     

Optimal injection solution for endoscopic submucosal dissection: A randomized controlled trial of Western solutions in a porcine model

Background and Aim

When carrying out endoscopic submucosal dissection (ESD), procedural safety increases with greater tissue elevation and efficiency increases with longer‐lasting submucosal cushion. Fluids specifically developed for ESD in Asia are not commercially available in the West, leaving endoscopists to use a variety of injectable fluids off‐label. To determine the optimal fluid available in the West, we compared commonly used fluids for Western ESD.

Methods

All phases were carried out in an ex vivo porcine stomach model. Phase 1 compared tissue elevation and duration of submucosal cushions produced by various standard volumes of various injectable solutions used for ESD. The two best‐performing solutions used off‐label were tested head‐to‐head in ESD in Phase 2. Phase 3 compared the best solution from Phase 2 to Eleview^®, currently the only submucosal injection fluid approved in the USA. In Phases 2 and 3, five ESD were carried out with each solution. The solutions were randomized and the endoscopist blinded to the solution.

Results

The best‐performing solutions in Phase 1 were 0.4% hyaluronic acid, 6% hydroxyethyl starch (HES), and Eleview^®. Phase 2 compared 6% HES and hydroxypropyl methylcellulose (HPMC), showing that ESD with 6% HES was easier (P = 0.007), faster (P = 0.041) and required less injection volume (P = 0.003). In Phase 3, resection speed, ease of ESD and total volume per area resected were comparable between 6% HES and Eleview^®.

Conclusions

Of the submucosal injection fluids currently available in the West, Eleview^® and 6% HES are the best‐performing solutions for ESD in a porcine model.     

Investigation of ulcer healing after esophageal EMR/ESD

Background  

Endoscopic mucosal resection (EMR) for early esophageal cancer has become popular. Recently, endoscopic submucosal dissection (ESD) has been used to excise widespread lesions en bloc. However, the time required for the ulcer to heal has not been clarified. Therefore, we investigated the healing time of ulcers that were formed after EMR/ESD.     

Endoscopic Submucosal Dissection of Gastric Neoplasia Involving the Pyloric Channel by Retroflexion in the Duodenum

Background  

Tumors involving the pyloric channel have been considered as difficult lesions for successful endoscopic resection. We studied the feasibility of endoscopic submucosal dissection (ESD) using retroflexion in the duodenum to resect the gastric neoplasia involving the pyloric channel.     

Safe and effective sedation in endoscopic submucosal dissection for early gastric cancer: a randomized comparison between propofol continuous infusion and intermittent midazolam injection

Purpose  

Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) generally takes longer to perform than conventional endoscopy and usually requires moderate/deep sedation with close surveillance for patient safety. The aim of this study was to compare the safety profiles and recovery scores propofol continuous infusion and intermittent midazolam (MDZ) injection as sedation for ESD.     

Expression of VEGF,EGFR, and IL-6 in Gastric Adenomas and Adenocarcinomas by Endoscopic Submucosal Dissection

Background  

The degree of intratumoral microvascular density is thought to affect tumor metastasis and prognosis in various human cancers, including gastric cancer. Despite recent medical advancements, gastric adenoma or adenocarcinoma remains a considerable therapeutic challenge. Endoscopic submucosal dissection (ESD) is a more recent approach that is now commonly used for radical resection of gastric adenoma and adenocarcinoma.     

Safety and efficacy of colorectal endoscopic submucosal dissection in elders: clinical and follow-up outcomes

Purpose

Endoscopic submucosal dissection (ESD) has recently been applied to treatment of colorectal neoplasia; however, its safety and efficacy in terms of follow-up outcomes in elders have not been thoroughly examined. The aim of this study is to describe the clinical outcomes of colorectal ESD in elderly patients.

Methods

Two groups of patients, elderly (≥75?years of age) and non-elderly (<75?years of age), who underwent colorectal ESD at the National Cancer Center Hospital from February 1998 to December 2010 were retrospectively compared on the following measures: tumor size, procedure time, complication rates, en bloc resection rates, and curative resection rates. We also investigated the follow-up outcomes in non-curative resection cases.

Results

Of 614 consecutive patients treated by colorectal ESD, 125 (20.4?%) comprised the elderly group, and 489 patients (79.6?%) comprised the non-elderly group. No significant differences were observed between the two groups in terms of tumor size, procedure time, complication rates, en bloc resection rates, and curative resection rates. Of the patients who underwent non-curative resection, 7/19 (36.8?%) and 47/63 (74.6?%) in the elderly and non-elderly group, respectively, underwent additional treatment. Among the elderly patients who were followed up without additional treatment, no case of local recurrence, residual lesions, or distant metastases was observed during the observation period.

Conclusion

Treatment outcomes of colorectal ESD were equivalent in both groups. However, many of the non-curative cases in the elderly patients were followed up without additional treatment. Future studies should focus on the outcome in such patients to confirm the feasibility of colorectal ESD in elderly patients.     

Risk factors for vertical incomplete resection in endoscopic submucosal dissection as total excisional biopsy for submucosal invasive colorectal carcinoma

Purpose

Endoscopic submucosal dissection (ESD) for colorectal tumor is a minimally invasive treatment. Histologic information obtained from the entire ESD specimen is important for therapy selection in submucosal invasive colorectal carcinoma (SMca). This study aimed to identify risk factors for vertical incomplete resection (vertical margin-positive [VM+]) when ESD was performed as total excisional biopsy for SMca.

Methods

From June 2003 through December 2011, 78 SMca cases were resected by ESD at Hiroshima University Hospital. Patient and tumor characteristics, intraoperative variables, and histopathology were compared between the VM+ group and the vertical complete resection (vertical margin-negative) group. The ability of magnifying endoscopy (ME) and endoscopic ultrasonography (EUS) to predict VM+ was assessed.

Results

ESD resulted in VM+ in eight cases (10.3 %), with a greater percentage invading to a depth of ≥2,000 vs. <2,000 μm (P?=?0.047). Severe submucosal fibrosis was found in five of the eight cases (62.5 %, P?=?0.017). Poor differentiation was seen at the deepest invasive portion in six cases (75.0 %), and two of six cases had an invasion depth <2,000 μm. Of 39 EUS cases, 36 not showing deep invasion close to the muscularis propria were completely resected by ESD.

Conclusions

Submucosal fibrosis and poor differentiation at the deepest invasive portion may be risk factors for VM+ in colorectal ESD for tumors with submucosal deep invasion. ME plus EUS is more likely to help determine whether ESD is indicated as complete total excisional biopsy for SMca.     

Outcome of endoscopic submucosal dissection for colorectal tumors in elderly people

Background

Endoscopic submucosal dissection (ESD) has been reported to be effective for the en bloc resection of large colorectal tumors. Our study investigated whether ESD was suitable for elderly people with large colorectal tumors in terms of its invasiveness.

Patients and methods

We studied 119 colorectal tumors that were treated with ESD at Kyoto Prefectural University of Medicine or Nara City Hospital between 2006 and 2009. We classified each patient as either elderly, i.e., more than 75 years old, or non-elderly, i.e., less than 75 years old. Thirty-two of the cases were classified as elderly. Performance status, tumor size, operation time, rate of en bloc resection, histopathological diagnosis, complications, and hospital stay after ESD were analyzed retrospectively in both groups.

Results

In the elderly group, the average tumor size was 32.6 mm; the average operation time, 96 min; the rate of en bloc resection, 81.2%; the rate of perforation, 3.1%; and hospital stay after ESD, 5.1 days. Histopathological diagnosis for 16 tumors was adenoma; for 13, carcinoma with invasion into the mucosa; and for three, carcinoma with invasion into the submucosa. There were no statistical differences between the two groups in any of these data. The case with perforation was treated conservatively without urgent surgery in the elderly group.

Conclusions

ESD for colorectal tumors resulted in favorable rates of en bloc resection in elderly people. Perforation occurred in elderly people, but these patients were cured with conservative treatment. ESD is a safe and minimally invasive treatment for elderly people with colorectal tumors.     

Effect of lansoprazole versus roxatidine on prevention of bleeding and promotion of ulcer healing after endoscopic submucosal dissection for superficial gastric neoplasia

Background  

Proton pump inhibitors have been reported to be more useful than histamine-2 receptor antagonists for the prevention of bleeding after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia. The aim of this study was to assess the effects of the proton pump inhibitor lansoprazole and the histamine-2 receptor antagonist roxatidine for the prevention of bleeding and the promotion of ulcer healing after ESD and to compare the cost-effectiveness of these two drugs.     

Colorectal lateral spreading tumor subtypes: clinicopathology and outcome of endoscopic submucosal dissection

Purpose

This study aims to investigate the clinicopathological features of specific subtypes of laterally spreading tumor (LST) and assessed the outcome of endoscopic submucosal dissection (ESD) based upon subdifferentiation status.

Methods

A total of 137 LSTs were present in 135 patients; 96 were granular and 41 exhibited a nongranular pattern. Granular LSTs, subdivided into homogeneous and nodular mixed, and nongranular LSTs, subdivided into flat-elevated and pseudodepressed, were retrospectively evaluated with respect to clinicopathological features and results of ESD (en bloc R0 curative resection, procedure time, complication, and recurrence rate) according to specific subtype.

Results

The distribution of high-grade intraepithelial neoplasia and submucosal carcinomas was more prominent among granular nodular mixed tumors than among granular homogeneous tumors (P?=?0.007), whereas there was no significant difference between nongranular pseudodepressed tumors and flat-elevated tumors. The frequency of en bloc R0 curative resection did not differ significantly among specific subtypes. For nodular mixed and pseudodepressed lesions, the median tumor size was significantly larger (P?<?0.001 for each) and mean procedure time was also longer (P?<?0.05 for each) than for the other two subtypes. All complications, which included three perforations, five episodes of postoperative bleeding, and one recurrence, occurred in granular nodular mixed and nongranular pseudodepressed tumors.

Conclusion

The risk of cancer varies with the subtypes of LSTs. ESD is an effective treatment for LSTs, however ESD is more technically demanding and carries more complications in pseudodepressed and granular mixed subtypes.     

The efficacy of endoscopic submucosal dissection for colorectal tumors extending to the dentate line

Purpose

Although endoscopic submucosal dissection (ESD) is becoming the mainstay of the treatment strategies, rather than surgical treatment, for colorectal tumors extending to the dentate line, ESD is technically more difficult. This study was aimed at assessing the usefulness of ESD for the treatment of colorectal tumors extending to the dentate line.

Methods

This study included 531 patients with colorectal tumors who underwent colorectal ESD between 2008 and 2015. They were divided into three groups: rectal tumors extending to the dentate line (anorectal group), those not extending to the dentate line (proximal rectal group), and colonic tumors (colonic group), and a retrospective comparative analysis was carried out.

Results

Of the total patients, 18 (3.4%) had lesions extending to the dentate line area. The procedure times were 103.4 ± 84.0, 80.4 ± 64.3, and 71.8 ± 52.3 min, respectively (P = 0.0318). All the patients in the anorectal group were operated by operators who had performed at least 20 colorectal ESDs (P < 0.0001). No significant difference among the three groups was found in the en bloc resection rate, complete resection rate, or curative resection rate. Although no significant difference in the incidence of perforation was observed among the three groups, intraoperative bleeding was observed in 61% of the patients in the anorectal group (P < 0.0001).

Conclusions

ESD is an effective treatment strategy for colorectal tumors extending to the dentate line. However, it seems that anorectal ESD, which is technically more difficult than colorectal ESD, should be performed by operators with ample experience in performing ESD.

     

Treatment of gastric epithelial tumours by endoscopic submucosal dissection using an insulated-tip diathermic knife

BACKGROUND:

Endoscopic submucosal dissection (ESD) is a promising technique for the treatment of large, pre- and early malignant gastrointestinal lesions.

OBJECTIVE:

To assess the rates of en bloc resection, incidence of complications, procedure times and therapeutic outcomes of ESD using an insulated-tip diathermic knife; and to investigate predictors of these outcomes based on the final pathological features of biopsy specimens.

METHODS:

One hundred twenty patients with endoscopically suspected gastric epithelial tumours who were treated with ESD from January 2006 to December 2009 were evaluated.

RESULTS:

The mean diameter of the gastric epithelial tumours in the present cohort was 1.88 cm. The mean diameter of the resected specimens was 3.33 cm. The en bloc resection rate was 90% (108 of 120). The median length of the operation was 64.6 min. The bleeding and perforation complication rates were 5.0% (six of 120) and 2.5% (three of 120), respectively. Of 10 gastric tumours initially diagnosed as adenocarcinoma on biopsy, four were found to be low-grade dysplasia and six were found to be high-grade dysplasia after resection and final pathological examination. A total of 112 (93.33%) patients underwent curative treatment, eight patients (6.67%) underwent noncurative treatment with ESD, and two patients (1.67%) experienced local recurrence and subsequently underwent surgery.

CONCLUSIONS:

ESD is a promising local curative treatment option for gastric epithelial tumours, but still carries the risks of bleeding and/or perforation. Differences in the interpretation of histological results among different pathologists and/or between biopsy specimens before ESD and the en bloc tissue specimens after ESD will result in discrepancies.     

Long-term outcomes of colorectal endoscopic submucosal dissection in elderly patients

Background and aims

The safety and efficacy of endoscopic submucosal dissection (ESD) in elderly patients remain unclear. The aim of this study is to clarify the short- and long-term outcomes of colorectal ESD in elderly patients.

Patients and methods

A total of 482 consecutive patients with 501 colorectal lesions treated with ESD from February 2005 to December 2013 were retrospectively reviewed. Patients were divided into two groups: an elderly group (≥ 75 years of age) and a non-elderly group (< 75 years of age). Short-term outcomes of interest were procedure time, complication rate, hospital stay, en bloc resection rate, and non-curative resection rate. Long-term outcomes of interest were disease-specific survival, and overall survival rates in the elderly group (51 patients) and non-elderly group (92 patients) were also analyzed.

Results

No significant differences were observed between the groups with respect to short-term outcomes. Two patients in each group required emergency surgery. Of the patients who underwent non-curative resection, 7/12 (58%) in the elderly group and 15/23 (65%) in the non-elderly group underwent additional surgery. The 5-year disease-specific survival rates in the elderly and non-elderly groups were both 100%, and the corresponding 5-year overall survival rates were 86.3 and 93.5%, respectively (p = 0.026).

Conclusions

Short-term outcomes after colorectal ESD were equivalent in both groups, and all patients showed favorable long-term outcomes. Considering the benign prognosis of lesions resected with ESD, preoperative screening of comorbidities is essential to improve overall survival.

     

Contributing Factors to Gastric Ulcer Healing After Endoscopic Submucosal Dissection Including the Promoting Effect of Rebamipide

Background  

The healing process for artificial ulcers resulting from endoscopic submucosal dissection (ESD) for gastric cancer is not understood.     

Efficacy of preemptive endoscopic submucosal dissection and surgery for synchronous colorectal neoplasms

Abstract

Background and aim

If patients with surgically resectable colorectal cancershave synchronous colorectal neoplasms that are difficult to remove by endoscopic mucosal resection, preemptive endoscopic submucosal dissection (ESD) can avoid excessive colorectal resection. The aim of this study was to evaluate the efficacy of the strategy of preemptive ESD and surgery for synchronous colorectal neoplasms.     

An evaluation of resectability among endoscopic treatment methods for rectal neuroendocrine tumors <10 mm

Background and Study AimsWith respect to rectal neuroendocrine tumor (NET) resection, it remains unclear which of the following methods is the most effective: conventional endoscopic mucosal resection (cEMR), EMR using a fitted cap (EMR-C), EMR with a ligation band device (EMR-L), or endoscopic submucosal dissection (ESD). Thus, in this study, we aim to retrospectively evaluate the most effective endoscopic resection for rectal NETs < 10 mm.Patients and methodsIn total, 61 consecutive patients with primary rectal NETs < 10 mm in diameter were included in this study; they were then divided into three groups: those with cEMR; those with modified EMR (mEMR) involving EMR-C and EMR-L; and those with ESD. The primary endpoint was to evaluate the difference in the complete en bloc resection rate. The secondary endpoint was to investigate differences in procedure time and complications.ResultsAmong the three groups, a significant difference was found in procedure time (cEMR vs ESD, P < .01; mEMR vs ESD, P < .01), en bloc resection rate (cEMR vs mEMR, P = .015), tumor size (mEMR vs ESD, P < .01), percentage of tumor diameter ≥ 5 mm (mEMR vs ESD, P < .01), and complete en bloc resection rate (cEMR vs mEMR, P = .014). Meanwhile, no significant difference was noted in terms of complication rate among the three groups.ConclusionThe mEMR was the most suitable resection method for rectal NETs < 10 mm with respect to the risks and benefits from procedure-related factors, such as complete en bloc resection rate, procedure time, and complication rate.