Shusei Fukunaga

Learning curve associated with colorectal endoscopic submucosal dissection for endoscopists experienced in gastric endoscopic submucosal dissection.

BACKGROUND: Colorectal endoscopic submucosal dissection requires a high level of skill and experience in therapeutic endoscopy because of the high risk of complications such as perforation and bleeding. Greater understanding of the procedural learning curve is required to standardize training and to achieve wider acceptance of this procedure. OBJECTIVE: The aims of this study were to evaluate the clinical outcomes of colorectal endoscopic submucosal dissection and to clarify its learning curve for endoscopists. DESIGN: We retrospectively reviewed the clinical outcomes for consecutive patients with colorectal neoplasms who underwent endoscopic submucosal dissection by 2 trainees under the guidance of experienced specialists. SETTING: The study was performed at the National Cancer Center Hospital, Tokyo, Japan. PATIENTS: Colorectal endoscopic submucosal dissections were performed for 101 consecutive patients with 102 colorectal neoplasms between April 2008 and December 2010. MAIN OUTCOME MEASURES: Procedure time, en bloc resection rate, completion rate, and complications were retrospectively compared between 4 training periods in which each trainee performed 10 endoscopic submucosal dissections per period and a final training period in which the trainees performed 10 to 12 endoscopic submucosal dissections to analyze the skill improvement with time. RESULTS: The procedure time and en bloc resection rate were not significantly different among the training periods. However, the completion rates in the fourth (100%) and fifth (95.5%) training periods (≥31 cases/trainee) were significantly higher (P < .001) than those in the first (45%), second (70%), and third (80%) training periods (1–30 cases/trainee). Two cases of perforation occurred during the study. LIMITATIONS: Limitations include the single-center design. Training programs and instruments vary with institution, which could affect the learning curve. CONCLUSIONS: Trainee endoscopists are able to perform colorectal endoscopic submucosal dissection without serious complications under the guidance of experienced specialists. They can perform it safely and independently after preparatory training and experience with ≥30 cases.

Endoscopic submucosal dissection (ESD) for colorectal tumors.

Background:  Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, however, it is not widely used in the colorectum because of its technical difficulty.

Treatment strategy for recurrent or residual colorectal tumors after endoscopic resection

BackgroundPiecemeal resection of colorectal neoplasms is associated with a higher risk of recurrent or residual tumors, but nearly all such cases can be cured by additional endoscopic resection (ER). Although the adoption of endoscopic submucosal dissection (ESD) for colorectal neoplasm is continuing, the safety of this treatment for recurrent or residual tumors has not been fully assessed. We evaluated salvage therapy for the treatment of recurrent or residual tumors, and propose an endoscopic treatment strategy for these tumors.MethodsThis retrospective study was conducted for 60 consecutive patients who had with locally recurrent or residual tumor after ER between January 2004 and October 2005. Endoscopic treatment strategy, treatment results, complications and clinical outcomes were recorded.ResultsAmong 69 lesions in 60 patients, 67 were treated endoscopically, whereas 2 required surgical treatment. Of these 67, 87% (58/67) were resected by endoscopic mucosal resection (EMR) and 13% (9/67) by ESD. En bloc resection rate was 39% (23/58) in the EMR group and 56% (5/9) in the ESD group. One limitation of this study is that it was a single-center retrospective analysis.ConclusionsESD is safe and effective for the treatment of recurrent or residual colorectal tumors. However, because of its technical difficulty, the en bloc resection rate is lower than that for the treatment of nonrecurrent lesions.

Risk Factors for Delayed Bleeding After Endoscopic Resection for Large Colorectal Tumors

OBJECTIVE Endoscopic resection techniques for treating colorectal tumors have advanced recently so that large colorectal tumors can now be treated endoscopically, although some patients experience delayed bleeding after endoscopic resection. Our aim was to clarify the risk factors for delayed bleeding after endoscopic resection for colorectal tumors≥20 mm in diameter. Endoscopic submucosal dissection cases were excluded because of the low incidence of delayed bleeding after such procedures. METHODS This was a retrospective study using a prospectively completed database and patient medical records at a single, national cancer institution. A total of 403 colorectal endoscopic resections were performed on 375 consecutive patients. We analyzed the database and retrospectively assessed patient age, gender, hypertension and current use of anticoagulant (warfarin) or antiplatelet drugs (e.g. aspirin, ticlopidine) as well as tumor location, size, macroscopic type, histopathological findings, resection method and whether or not placement of prophylactic clips was performed during the endoscopic resection. RESULTS The overall rate of delayed bleeding was 4.2% (17/403) and the median interval between endoscopic resection and the onset of delayed bleeding was 2 days (range, 1-14 days). All delayed bleeding cases were successfully controlled by endoscopic hemostasis involving clipping and/or electrocoagulation without the need for surgical interventions or blood transfusions. Based on our univariate analysis, the delayed bleeding rate was significantly higher in both males (P=0.04) and those patients without prophylactic clip placement (P=0.04). CONCLUSIONS Our study results indicated that prophylactic clip placement may be an effective method for preventing delayed bleeding after endoscopic resection for large colorectal tumors.

Clinical Efficacy of Endoscopic Submucosal Dissection for Adenocarcinomas of the Esophagogastric Junction.

Background and Study Aims There are a few reports about the efficacy of endoscopic submucosal dissection (ESD) for adenocarcinomas of the esophagogastric junction (EGJ). However, there is no detailed analysis that divides EGJ cancers into Barrett’s adenocarcinoma and gastric cardia adenocarcinoma. The aim of this study was to analyze the efficacy of ESD for EGJ cancers, comparing these two adenocarcinomas. Patients and Methods This study included 43 patients who underwent ESD for type II EGJ cancers between 2004 and 2011. Pathological examination of resected specimens confirmed 14 cases of Barrett’s adenocarcinoma and 29 cases of gastric cardia adenocarcinoma. Cutting margins on the oral side were placed 1 cm from the squamocolumnar junction, or 1 cm away from the slight elevation that is an endoscopic sign of subsquamous carcinoma extension. Clinical outcomes, prevalence and length of subsquamous carcinoma extension, and long-term outcomes were compared between these two types of adenocarcinoma. Results No significant differences in clinical outcomes were found between these two types of adenocarcinoma (en bloc, 100 % versus 100 %; complete, 100 % versus 89.7 %; curative, 85.7 % versus 75.9 %). No serious adverse events were encountered. The prevalence of subsquamous carcinoma extension was significantly higher in Barrett’s adenocarcinoma compared with gastric cardia adenocarcinoma. Local and distant recurrence were not observed in any cases with curative resection during the follow-up period (1.6 – 87.6 months). Conclusion ESD for EGJ cancers, including both Barrett’s adenocarcinoma and gastric cardia adenocarcinoma, was efficient and useful. ESD with a 1 cm safety margin may be acceptable for EGJ cancers.

The five-year survival rate after endoscopic submucosal dissection for superficial esophageal squamous cell neoplasia

BACKGROUND Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell neoplasia (ESCN) because of a high complete resection rate. However, there were a few reports about the long-term outcomes of these patients due to short follow-up periods. AIMS We aimed to evaluate the 5-year survival after ESD for superficial ESCN. METHODS This was a retrospective cohort study performed at a single institution. Between 2006 and 2009, 94 patients with superficial ESCN underwent ESD. Eighty-three patients (93.3%) who had completed an extended period of observation of at least 5 years were enrolled. The main outcomes were the 5-year survival rates. The secondary outcomes were the cumulative incidence rate of metachronous ESCN, and the clinical outcomes. RESULTS The 5-year relative overall survival rate was 99.0%, whereas the cause specific survival rate was 100% during 72.9 months of median follow up period. Subgroup analysis showed that the 5year survival of patients with EP/LPM and MM/SM1 (submucosal invasion ≤200μm) were 100% and 89.0%, respectively. The cumulative incidence rate of metachronous ESCN at 5 years was 16.8%. CONCLUSION ESD for superficial ESCN is a curative treatment with a favorable 5-year survival rate.

The prevalence of adverse events associated with double-balloon enteroscopy from a single-centre dataset in Japan

BACKGROUND There are few comprehensive reports detailing the prevalence of major adverse events associated with a double-balloon enteroscopy procedure. METHODS We retrospectively investigated the prevalence of major adverse events in 538 patients (262 males and 276 females; median age, 65 years; age range, 12-95 years) who underwent double-balloon enteroscopy at our Institution between April 2008 and October 2011. RESULTS Of the 17 adverse events recorded (3.2%), acute pancreatitis (n=5; 0.9%) occurred during both diagnostic (n=3) and therapeutic (n=2) anterograde double-balloon enteroscopy, and all of them were treated conservatively. For these cases, the average duration of the examination was 135 min, which was longer than for the other patients (97 min) (P=0.046). Intestinal bleeding (1.3%) was observed in 6 cases after endoscopic polypectomy and in 1 case following a biopsy procedure during a diagnostic double-balloon enteroscopy. The prevalence rates of intestinal perforation and other complications were 0.2% and 0.7%, respectively. CONCLUSIONS The rate of adverse events associated with double-balloon enteroscopy was high compared to that associated with conventional upper/lower gastrointestinal endoscopy (0.042%/0.078%). The occurrence of acute pancreatitis may be significantly dependent on the duration of double-balloon enteroscopy examination.

Impact of endoscopic submucosal dissection knife on risk of perforation with an animal model-monopolar needle knife and with a bipolar needle knife

The bipolar needle knife (B knife; XEMEX Co, Tokyo, Japan) was developed to reduce the risk of perforation during endoscopic submucosal dissection compared to monopolar instruments (Fig. 1a). It was designed so highfrequency electricity flows from the knife to the sheath tip, reducing the amount of current sent to the muscle layer (Fig. 2a). Subsequently, the ball-tip B knife (BB knife; XEMEX) was designed with a ball-shaped needle end, to further reduce the risk of perforation (Fig 1b). The objective of this animal experiment was to confirm and compare the actual risk of perforation with these different knives. A resected porcine esophagus was cut open along the long axis to expose the lumen, which was fixed to a tray with stable tension. The end of each endoscopic submucosal dissection knife attached to a stick was designed to perpendicularly contact the mucosa.A 200 g fixed weight attached to the stick created a constant pressure for each application. A 40 W forced coagulation current (ICC200; ERBE, Tübingen, Germany) was applied with a needle knife (Olympus Optical Co., Ltd, Tokyo, Japan) (Fig. 1c), B knife and BB knife, and perforation time was measured.This procedure was repeated 10 times for each knife. The time to perforation (mean SD) with the needle knife, B knife and BB knife was 0.5 0.2, 4.0 1.3 and 5.1 1.6 s, respectively (needle vs B, P < 0.001; B vs BB, not significant; needle vs BB, P < 0.001) (Fig. 2b). The B and BB knives had significantly longer times to perforation than the needle knife. Bipolar instruments are considered safer because of their perceived reduced risk of perforation, particularly the BB knife with its ball-tipped design. Our study reaffirmed that bipolar knives are better for performing endoscopic submucosal dissection of the esophagus and colorectum, which have thinner walls than the stomach.

Hybrid therapy with locoregional steroid injection and polyglycolic acid sheets to prevent stricture after esophageal endoscopic submucosal dissection

Background and study aim: The incidence of stricture formation caused by endoscopic submucosal dissection (ESD) for widespread lesions is high, and stricture formation can reduce quality of life. We evaluated the prophylactic efficacy of hybrid therapy using a locoregional steroid injection and polyglycolic acid (PGA) sheets with fibrin glue to prevent stricture formation after esophageal ESD in high risk patients in whom we predicted stricture formation would be difficult to prevent with a single prophylactic steroid injection. Methods: Ten patients who underwent esophageal ESD were enrolled (entire-circumference: n = 6; sub-circumference, more than 5/6 of the circumference: n = 4). A single locoregional steroid injection and PGA sheets with fibrin glue were used after ESD. We evaluated the incidence of stricture formation, the number of endoscopic balloon dilation (EBD) procedures needed to treat the stricture formation, and adverse events of the therapy. Results: Esophageal stricture formation occurred in 50.0 % of patients (5/10) (median EBD sessions 0.5, range 0 – 16). Subanalysis showed that stricture formation occurred in 37.5 % of patients (3/8) excluded the lesions located near a previous scar from ESD or surgical anastomosis site (median EBD sessions 0, range 0 – 4). Conclusion: Hybrid therapy using a locoregional steroid injection and PGA sheets with fibrin glue may have the potential to prevent esophageal stricture formation after esophageal ESD in high risk patients.

Prediction of Poor Response to Modified Neuroleptanalgesia with Midazolam for Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma

Background/Aims: Modified neuroleptanalgesia (m-NLA) with midazolam is often used for sedation and analgesia during endoscopic submucosal dissection (ESD) for gastrointestinal neoplasia. However, interruption due to poor response to midazolam is often experienced during ESD for esophageal squamous cell carcinoma (ESCC) because most patients with ESCC have a history of heavy alcohol intake. We examined the incidence and risk factors for poor response to m-NLA with midazolam and pethidine hydrochloride. Methods: This retrospective cross-sectional study was conducted at a single institution. Between April 2007 and July 2013, 151 patients with superficial ESCC who underwent ESD under sedation using m-NLA with midazolam and pethidine hydrochloride were enrolled. Poor response to sedation was defined as the use of a second drug when Ramsay Sedation Score 1-2. Results: Poor response to sedation occurred in 66.2% patients. Most cases of poor response were controlled by using additional flunitrazepam. Multivariate logistic regression analysis showed that cumulative alcohol intake and major specimen size were independent risk factors for poor response to sedation (OR 3.63, 95% CI 1.20-10.99, and OR 3.23, 95% CI 1.26-8.25). Conclusion: Our study indicated that cumulative alcohol intake and major specimen size were associated with poor response to m-NLA with midazolam and pethidine hydrochloride.