Noboru Hanaoka

Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: a controlled prospective study

BACKGROUND AND STUDY AIMS The frequency of stricture after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma with a mucosal defect involving more than three-quarters of the circumference is 70% - 90%. Stricture decreases quality of life and requires multiple endoscopic balloon dilation (EBD) sessions. We investigated the efficacy and safety of a single session of intralesional steroid injections to prevent post-ESD stricture. PATIENTS AND METHODS We conducted a prospective study on 30 patients with esophageal squamous cell carcinoma treated by ESD, who had a more than three-quarter but less than whole circumferential defect. A single session of intralesional steroid injections was undertaken immediately after ESD. Esophagogastroduodenoscopy was performed whenever patients reported dysphagia and 2 months after ESD in patients without dysphagia. Results were compared with a historical control group of 29 patients who underwent ESD without intralesional steroid injection. The primary endpoint was the post-ESD stricture rate. Secondary endpoints were the number of EBD sessions and the complication rate. RESULTS Compared with the historical control group, the study group had a significantly lower stricture rate (10%, 3/30 patients vs. 66%, 19/29 patients; P < 0.0001) and a lower number of EBD sessions (median 0, range 0 - 2 vs. median 2, range 0 - 15; P < 0.0001). The study group had a complication rate of 7 % (2 /30 patients), comprising a submucosal tear in one patient and bleeding in another, which were not a direct result of EBD. CONCLUSIONS A single session of intralesional steroid injections showed promising results for the prevention of stricture after ESD for esophageal cancer.

Mixed-histologic-type submucosal invasive gastric cancer as a risk factor for lymph node metastasis: feasibility of endoscopic submucosal dissection

BACKGROUND AND STUDY AIMS The clinicopathologic features of gastric cancers containing a mixture of differentiated-type and undifferentiated-type components remain uninvestigated. We evaluated the risk of lymph node metastasis and the feasibility of endoscopic submucosal dissection (ESD) for the treatment of mixed-histologic-type gastric cancers. PATIENT AND METHODS We histologically classified 376 cases of gastric cancer with submucosal invasion into four types (differentiated type, differentiated-type-predominant mixed type, undifferentiated-type-predominant mixed type, and undifferentiated type) and studied the clinicopathologic relations of each type to lymph node metastasis. Lymphatic invasion was evaluated by D2-40 immunostaining. RESULTS The overall prevalence of lymph node metastasis in gastric cancer with submucosal invasion was 16.5% (62/376). The prevalence of lymph node metastasis was 36.5% (23/63) in undifferentiated-type-predominant mixed type, which was significantly higher than those in the other three types (P < 0.001 vs. differentiated type, P = 0.013 vs. differentiated-type-predominant mixed type, and P = 0.003 vs. undifferentiated type). Lymphatic invasion, a depth of invasion of 500 microm or more from the lower margin of the muscularis mucosae (SM2), tumor size above 30 mm, and undifferentiated-type-predominant mixed histologic type were independent risk factors for lymph node metastasis. Submucosal cancers without these four risk factors were free of lymph node metastasis (0/41; 95 % confidence interval 0%-8.6%). CONCLUSIONS Undifferentiated-type-predominant mixed-type gastric cancer with submucosal invasion carries a high risk of lymph node metastasis. ESD can be indicated for gastric cancer with submucosal invasion provided that the following conditions indicating a low risk of metastasis are met: a depth of invasion of no more than 500 microm or more from the lower margin of the muscularis mucosae (SM1), no lymphatic invasion, a tumor size of no more than 30 mm, and a proportion of undifferentiated components below 50%.

Efficacy of an Endo-Knife With a Water-Jet Function (Flushknife) for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms

OBJECTIVES:Endoscopic submucosal dissection (ESD) is currently not a common treatment for colorectal neoplasms because it is time consuming and technically difficult. Flushknife—an electrosurgical endo-knife with a water-jet function—is expected to reduce the difficulty of colorectal ESD. The objective of this study was to investigate the efficacy of a water-jet function for colorectal ESD.METHODS:This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. A total of 49 patients, with a total of 51 superficial colorectal neoplasms (median tumor size of 30 mm), were enrolled and randomly assigned to undergo ESD using either the Flexknife (electrosurgical endo-knife without a water-jet function) or the Flushknife. Tumors were resected by ESD using each endo-knife. The procedures were conducted by two endoscopists. Operation time was defined as the main outcome measure.RESULTS:En bloc resection was achieved in 23 out of 26 (88%) lesions in the Flexknife group and in 24 out of 24 (100%) lesions in the Flushknife group. The mean operation time (95% confidence interval) was 87.3 (71.3–103.4) min in the Flexknife group and 61.0 (49.3–72.7) min in the Flushknife group (P=0.02). The Flushknife reduced the number of endoscopic device changes (P=0.001), the number of submucosal injections (P=0.001), and the mean amount of injected hyaluronate sodium (P=0.001) compared with the Flexknife. No severe adverse events were observed in either group.CONCLUSIONS:Without increasing adverse events, the endo-knife with a water-jet function efficiently reduced the operation time of colorectal ESD in patients with large superficial colorectal neoplasms. (University hospital Medical Information Network Clinical Trials Registry number UMIN000001302)

Clinical features and outcomes of delayed perforation after endoscopic submucosal dissection for early gastric cancer

Perforation is a major complication of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). However, there have been no reports on delayed perforation after ESD for EGC. We aimed to elucidate the incidence and outcomes of delayed perforation after ESD. Clinical courses in 1159 consecutive patients with 1329 EGCs who underwent ESD were investigated. Delayed perforation occurred in six patients (0.45 %). All these patients had complete en bloc resection without intraoperative perforation during ESD. Five of six perforations were located in the upper third of the stomach, while one lesion was found in the middle third. Symptoms of peritoneal irritation with rebound tenderness presented within 24 h after ESD in all cases. One patient did not require surgery because the symptoms were localized, and recovered with conservative antibiotic therapy by nasogastric tube placement. The remaining five patients required emergency surgery. There was no mortality in this case series.

Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial

BACKGROUND Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions. OBJECTIVE To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms. DESIGN A 2 × 2 factorial designed, prospective, randomized, controlled trial. SETTING This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center. PATIENTS A total of 561 patients. INTERVENTIONS Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH--colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method. MAIN OUTCOME MEASUREMENT The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups. RESULTS Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93-1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002). LIMITATIONS Open trial performed in single cancer referral center. CONCLUSION AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH.

Long-Term Outcome and Metastatic Risk After Endoscopic Resection of Superficial Esophageal Squamous Cell Carcinoma

OBJECTIVES:Long-term outcomes after endoscopic resection (ER) provide important information for the treatment of esophageal carcinoma. This study aimed to investigate the rates of survival and metastasis after ER of esophageal carcinoma.METHODS:From 1995 to 2010, 570 patients with esophageal carcinoma were treated by ER. Of these, the 402 patients with squamous cell carcinoma (280 epithelial (EP) or lamina propria (LPM) cancer, 70 muscularis mucosa (MM) cancer, and 52 submucosal (SM) cancer) were included in our analysis. Seventeen patients had cancer invading into the submucosa up to 0.2 mm (SM1) and 35 patients had cancer invading into the submucosa more than 0.2 mm (SM2).RESULTS:The mean (range) follow-up time was 50 (4–187) months. The 5-year overall survival rates of patients with EP/LPM, MM, and SM cancer were 90.5, 71.1, and 70.8%, respectively (P=0.007). Multivariate analysis identified depth of invasion and age as independent predictors of survival, with hazard ratios of 3.6 for MM cancer and 3.2 for SM cancer compared with EP/LPM cancer, and 1.07 per year of age. The cumulative 5-year metastasis rates in patients with EP/LPM, MM, SM1, and SM2 cancer were 0.4, 8.7, 7.7, and 36.2%, respectively (P<0.001). Multivariate analysis identified depth of invasion as an independent risk factor for metastasis, with hazard ratios of 13.1 for MM, 40.2 for SM1, and 196.3 for SM2 cancer compared with EP/LPM cancer. The cumulative 5-year metastasis rates in patients with mucosal cancer with and without lymphovascular involvement were 46.7 and 0.7%, respectively (P<0.0001).CONCLUSIONS:The long-term risk of metastasis after ER was mainly associated with the depth of invasion. This risk should be taken into account when considering the indications for ER.

Factors predicting perforation during endoscopic submucosal dissection for gastric cancer.

BACKGROUND Perforation is a common complication of endoscopic submucosal dissection (ESD), but little is known about the relevant risk factors. OBJECTIVE To investigate the risk factors for perforation. DESIGN Retrospective study. SETTING A cancer referral center. PATIENTS A total of 1795 early gastric tumors in 1500 patients treated by ESD from July 2002 to December 2010 were included in the analysis. MAIN OUTCOME MEASUREMENTS The associations between the incidence of perforation and patient and lesion characteristics were investigated. RESULTS Perforation during ESD occurred in 50 lesions (2.8%). Univariate analysis identified tumor location (upper, middle, or lower stomach), tumor diameter (≤ 20 or >20 mm), and treatment period (lesions treated in the first or second period) as predictors of perforation. Multivariate analysis identified tumor location (upper stomach), tumor diameter (>20 mm), and treatment period (first half) as independent risk factors for perforation. The odds ratios were 2.4 (95% CI, 1.3-4.7; P = .006) for lesions in the upper stomach and 1.9 (95% CI, 1.0-3.5; P = .04) for lesions larger than 20 mm. Perforation risks were 5.4% for lesions in the upper stomach and 4.4% for lesions larger than 20 mm. Three patients required emergency surgery, but the rest of the patients were successfully treated with endoscopic clipping. There was no perforation-related mortality. LIMITATIONS Single-center, retrospective study design. CONCLUSIONS Lesions in the upper stomach and lesions larger than 20 mm were independent risk factors for perforation during ESD. Patients should be made aware of the estimated high risks of these lesions before undergoing ESD.

Delayed perforation: A hazardous complication of endoscopic resection for non-ampullary duodenal neoplasm

Perforation is a major complication of endoscopic resection for gastrointestinal neoplasms. However, little is known about delayed perforation after endoscopic resection for non‐ampullary duodenal neoplasm. The aim of the present study was to investigate the clinical features of delayed perforation after endoscopic resection for non‐ampullary duodenal neoplasm.

Original article: Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists

Narrow-band imaging (NBI) is a novel, noninvasive optical technique that uses reflected light to visualize the organ surface. However, few prospective studies that examine the efficacy of NBI screening for esophageal cancer have been reported. To compare the diagnostic yield of NBI endoscopy for screening of squamous mucosal high-grade neoplasia of the esophagus between experienced and less experienced endoscopists. Patients with a history of esophageal neoplasia or head and neck cancer received NBI endoscopic screening for esophageal neoplasia followed by chromoendoscopy using iodine staining. Biopsy specimens were taken from iodine-unstained lesions and the histological results of mucosal high-grade neoplasias served as the reference standard. The primary outcome was the sensitivity of NBI for detecting new lesions. The secondary outcome was the positive predictive value of NBI and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NBI in a per lesion basis. A total of 350 patients (170 by experienced endoscopists and 180 by less experienced endoscopists) underwent endoscopic examination. A total of 42 new mucosal high-grade neoplastic lesions (25 in the experienced endoscopist group and 17 in the less experienced endoscopist group) were detected. In the per-lesion-based analysis, the sensitivity was significantly higher in the experienced endoscopist group (100%; 25/25) compared with the less experienced endoscopist group (53%; 9/17) (P < 0.001). The positive predictive value of NBI was higher in the experienced endoscopist group than in the less experienced endoscopist group (45%, 25/55 vs. 35%, 9/26), although the difference was not significant (P = 0.50). The sensitivity of NBI in the less experienced endoscopist group was 43% in the former half of patients, and increased to 60% in the latter half of patients. In the per-patient-based analysis, the sensitivity of NBI was significantly higher in the experienced endoscopist group (100%) than in the less experienced endoscopist group (100 vs. 69%, respectively; P = 0.04). The positive predictive values of the experienced endoscopist group and the less experienced endoscopist group were similar, and were 48 and 47%, respectively. In conclusion, compared with the gold standard of chromoendoscopy with iodine staining, the sensitivity of NBI for screening of mucosal high-grade neoplasia was 100% with the experienced endoscopists but was low with the less experienced endoscopists. Electronic chromoendoscopy with NBI is a promising screening tool in these high-risk patients with esophageal mucosal high-grade neoplasia, particularly when performed by endoscopists with experience of using NBI.

Diagnostic features of sessile serrated adenoma/polyps on magnifying narrow band imaging: A prospective study of diagnostic accuracy

The narrow band imaging classification system (NBI International Colorectal Endoscopic [NICE] classification) classifies colorectal polyps very accurately. However, sessile serrated adenoma/polyps (SSA/Ps) pathologically resembles hyperplastic polyp and has a possibility to be left in situ on NICE classification. The aim of this study was to establish and evaluate new simple diagnostic features for SSA/Ps using magnifying narrow band imaging (M‐NBI).