Akira Dobashi

In vivo histologic imaging of the muscularis propria and myenteric neurons with probe-based confocal laser endomicroscopy in porcine models (with videos)

BACKGROUND The submucosal tunneling technique enables us to endoscopically access deeper tissue layers. Use of probe-based confocal laser endomicroscopy (pCLE) provides optical histologic imaging on the site. OBJECTIVE To determine the technical feasibility of ex vivo and in vivo pCLE imaging of the muscularis propria and myenteric neurons by using submucosal endoscopy with a mucosal flap safety valve (SEMF). DESIGN Acute porcine model study. SETTING Animal laboratory. INTERVENTION Two ex vivo and 6 in vivo porcine models were used. A submucosal space was created with SEMF, and a neuronal molecular probe was topically applied onto the muscularis. Confocal imaging of the stained muscularis was performed by using pCLE. The selected sites were sampled, and the histopathology of the sites was analyzed. MAIN OUTCOME MEASUREMENTS The two main outcome measures were the procedural success rate of submucosal access and the correlation between pCLE and histologic images. RESULTS Submucosal access to the pCLE study site was successful in all attempts (100%; 17/17 sites). The muscularis propria was visualized with pCLE in the ex vivo and in vivo porcine models in 83.3% of sites (20/24), and the neuron-like cells were identified in 41.7% of sites (10/24). LIMITATIONS Animal experiment. CONCLUSION The muscularis propria and myenteric neurons could be selectively visualized with pCLE in vivo.

Perspectives on narrow‐band imaging endoscopy for superficial squamous neoplasms of the orohypopharynx and esophagus

Narrow‐band imaging (NBI) is widely available and over the last decade has been applied as a detection and characterization technique for superficial neoplasms of the aerodigestive tract. The aims of the present study were to systematically review clinical trials of NBI endoscopy and to investigate an upgraded NBI system using a novel endoscope for superficial squamous neoplasms in the orohypopharynx and esophagus.

A double-blind, block-randomized, placebo-controlled trial to identify the chemical assistance effect of mesna submucosal injection for gastric endoscopic submucosal dissection

BACKGROUND Previous animal studies and a pilot clinical trial demonstrated that submucosal injection of a thiol compound called mesna could chemically soften connective tissues and thus facilitate endoscopic submucosal dissection (ESD). OBJECTIVE To evaluate whether mesna injection could reduce procedural times for gastric ESD. DESIGN Double-blind, block-randomized, controlled trial. SETTING University hospital. PATIENTS A total of 101 patients with superficial gastric cancer indicated for ESD were enrolled and randomly assigned to either the mesna or control (saline solution) group. INTERVENTION Traditional ESD was performed with a single bolus injection of mesna or saline solution. MAIN OUTCOME MEASUREMENTS Time for submucosal dissection (TSD). RESULTS En bloc resection was achieved for all lesions in the mesna group (53/53) and 51 of 52 lesions (98.08%) in the control group. TSD was not statistically different between the groups (18.62 ± 13.9 [mean ± SD] minutes for the mesna group and 24.58 ± 24.55 [mean ± SD] minutes for the control group; P = .128), and there were fewer time-consuming cases (times over 30 minutes) in the mesna group compared with controls (7/53 vs 15/52; P = .049). Multivariate regression analysis demonstrated that use of mesna, specimen size, and the presence of fibrous scars were significantly correlated with TSD (P < .05). LIMITATIONS Single-center study. CONCLUSION TSD was not significantly different between the mesna and control injection groups, but multivariate analysis indicated that mesna injection reduced procedural challenges associated with the submucosal dissection. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000003786.).

Narrow-Band Imaging Magnifying Endoscopy versus Lugol Chromoendoscopy with Pink-Color Sign Assessment in the Diagnosis of Superficial Esophageal Squamous Neoplasms: A Randomised Noninferiority Trial

Previous studies have shown the high diagnostic accuracy of narrow-band imaging magnifying endoscopy (NBI-ME) and Lugol chromoendoscopy with pink-color sign assessment (LCE-PS) for superficial esophageal squamous cell carcinoma (SESCC). However, there has been no controlled trial comparing these two diagnostic techniques. We conducted a randomized noninferiority trial to compare the diagnostic accuracy of NBI-ME and LCE-PS. We recruited patients with, or with a history of, squamous cell carcinoma in the head and neck region or in the esophagus. They were randomly assigned to either NBI-ME or LCE-PS. When lesions > 5 mm in diameter were found as brownish areas on NBI or as Lugol-voiding lesions (LVL), they were evaluated to determine whether they are SESCC on the basis of the findings of NBI-ME or PS in the LVL. NBI-ME and LCE-PS were completed in 147 patients each. There was no significant difference in all diagnostic values between the two techniques. Compared with LCE-PS, NBI-ME showed a significantly shorter examination time but a larger number of misdiagnosed lesions especially in patients with many irregularly shaped multiform LVLs. Compared with LCE-PS, NBI-ME might be similarly accurate and less invasive, but less reliable in patients with many LVLs, in the diagnosis of SESCC.

Can mechanical balloon dissection be applied to cleave fibrotic submucosal tissues? A pilot study in a porcine model

BACKGROUND AND STUDY AIMS Removal of a lesion containing an ulcer scar is one of the most challenging applications of endoscopic submucosal dissection (ESD). The present study examined whether a novel balloon dissector could cleave fibrotic submucosal tissue beneath ulcer scars. METHODS Six pigs were studied. Endoscopic mucosal resection (EMR) with ligation was performed at 7 or 8 sites in the stomach for each animal; 4 weeks later, 23 sites with a visible scar were selected for submucosal dissection. The procedure involved first creating a submucosal fluid cushion (SFC) by injecting either saline mixed with mesna or pure saline. A slender, compliant balloon with a diameter of 8, 13, or 18 mm was inserted into the SFC. The balloon was unfolded and thrust forward to cleave the fibrotic submucosa over approximately 5 cm. RESULTS Fibrotic submucosa was dissected within 90 seconds in 17 of 23 attempts. Isolating the ulcer scar from the muscularis with the SFC prior to balloon dissection and using a thinner balloon catheter both ensured a better dissection. CONCLUSIONS The fibrotic submucosa underlying post-EMR scars can be dissected with the novel balloon dissector, although the technique is less effective in cases with no sign of lifting.

Clinicopathological features of narrow-band imaging endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms.

To reveal clinicopathological features of narrow-band imaging (NBI) endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms. If a lesion diameter was smaller or same compared with a width of closed biopsy forceps, a lesion was defined to be an ultraminute lesion. Twenty-five consecutive patients with 33 ultraminute esophageal lesions that were removed by endoscopic mucosal resection were included in the present study. We conducted two questionnaire surveys of six endoscopists by their retrospective review of endoscopic still images. The six endoscopists evaluated the endoscopic findings of the ultraminute lesions on still images taken by conventional white-light imaging endoscopy and non-magnified NBI endoscopy in the first questionnaire, and taken by magnified NBI endoscopy in the second questionnaire. An experienced pathologist who was unaware of any endoscopic findings made histological diagnosis and evaluated immunoexpression of p53 and Ki67. The 33 ultraminute lesions were all determined to be either 11 high-grade intraepithelial neoplasias (HGIENs) or 22 low-grade intraepithelial neoplasias (LGIENs). The tumor diameters were histologically confirmed to be <3 mm. All of the ultraminute tumors were visualized as unstained areas and brownish areas by real-time endoscopy with Lugol dye staining and non-magnified NBI endoscopy, respectively. All of the ultraminute IENs were visualized as brownish areas by real-time non-magnified NBI endoscopy. Three of the 25 patients with the ultraminute IENs (12%) had multiple brownish areas (more than several areas) in the esophagus on real-time non-magnified NBI endoscopy. All of the ultraminute IENs were visualized as unstained areas by real-time Lugol chromoendoscopy. Twenty of the 25 patients (80%) had multiple unstained areas (more than several areas) in the esophagus on real-time Lugol chromoendoscopy. The first questionnaire survey revealed that a significantly higher detection rate of the ultraminute IENs on non-magnified NBI endoscopy images compared with conventional white-light imaging endoscopy ones (100% vs. 72%, respectively: P < 0.0001). The second questionnaire survey revealed that presence rates of any magnified NBI endoscopy findings were not significantly different between HGIENs and LGIENs. Proliferation, dilation, and various shapes of intrapapillary capillary loops indicated remarkably high presence rates of more than 90% in both HGIENs and LGIENs. Six of 22 LGIENs (27%) and 3 of 11 HGIENs (27%) show a positive expression for p53. None of peri-IEN epithelia was positive for p53. A mean of Ki67 labeling index of LGIENs was 33% and that of HGIENs 36%. Ki67 labeling index was significantly greater in the LGIENs and HGIENs compared with that in the peri-IEN epithelia. There were no significant differences in p53 expression and Ki67 labeling index between the HGIENs and LGIENs. Non-magnified/magnified NBI endoscopy could facilitate visualization and characterization of ultraminute esophageal squamous IENs. The ultraminute HGIENs and LGIENs might have comparable features of magnified NBI endoscopy and immunohistochemistry.

Quantitative analysis of VEGF-C mRNA of extrahepatic cholangiocarcinoma with real-time PCR using samples obtained during endoscopic retrograde cholangiopancreatography.

Abstract Objective. Vascular endothelial growth factor (VEGF)-C overexpression in extrahepatic cholangiocarcinoma (ECC) has been shown to be correlated with lymph node metastasis. The intensity of immunohistochemical staining of VEGF-C protein in surgical samples has been used as index of VEGF-C overexpression in previous studies. The aim of the study was to examine if VEGF-C overexpression in ECC could be preoperatively detected by using samples obtained during ERCP. Methods. Consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for biliary stricture during the study period were prospectively analyzed. VEGF-C mRNA was quantified by real-time PCR methods using endoscopic samples obtained during ERCP. The high intensity of immunohistochemical staining of VEGF-C protein in surgical samples was used for the reference standard of VEGF-C overexpression. The level of S100P mRNA which was a novel diagnostic marker of ECC was also quantified to evaluate whether the endoscopic samples contained ECC cells. Results. Twenty-five patients were enrolled in this study. Eighteen patients were diagnosed as ECC and seven patients were diagnosed as benign biliary structure. Nine of eighteen patients with ECC, who showed positive S100P mRNA in endoscopic samples and received surgical resection, were finally analyzed. Receiver operating characteristics analysis yielded VEGF-C mRNA cut-off value of 3.85 for detection of VEGF-C overexpression, and the diagnostic performance of VEGF-C mRNA measurement in the endoscopic sample for VEGF-C overexpression reached sensitivity of 75.0%, specificity of 100%, and accuracy of 88.9%. Conclusion. The quantification of VEGF-C mRNA of ECC with real-time PCR using endoscopic samples was useful for preoperative detection of VEGF-C overexpression.

Dual-focus versus conventional magnification endoscopy for the diagnosis of superficial squamous neoplasms in the pharynx and esophagus: a randomized trial.

BACKGROUND AND STUDY AIMS Conventional magnification narrow-band imaging (CM-NBI) endoscopy has demonstrated high diagnostic accuracy for superficial squamous neoplasms in the pharynx and esophagus. This study aimed to evaluate the diagnostic utility of the newly developed dual-focus NBI (DF-NBI) compared with that of CM-NBI. PATIENTS AND METHODS We recruited patients with squamous cell carcinoma (SCC) in the head and neck, or esophagus, or with a history of SCC. The primary endpoint of this prospective controlled non-inferiority trial was the sensitivity of DF-NBI and CM-NBI for detecting superficial carcinoma in the pharynx and esophagus. Secondary endpoints included other diagnostic values and the resolving power of each endoscope. Superficial carcinoma was defined as high grade dysplasia and SCC invading up to the submucosal layer. RESULTS The study included 93 patients. A total of 28 superficial carcinomas were detected in the pharynx and esophagus. The sensitivities of DF-NBI and CM-NBI for superficial carcinoma were 82 % and 71 %, respectively. The lower limit of the 90 % confidence interval for the difference between the sensitivities exceeded the non-inferiority threshold. The specificity and overall accuracy of DF-NBI vs. CM-NBI were 93 % vs. 90 % and 91 % vs. 86 %, respectively (both non-significant differences). The maximum resolving power of a conventional magnification endoscope was significantly higher than a dual-focus endoscope (7.2 µm vs. 11.6 µm: P < 0.001). CONCLUSIONS The findings indicate the non-inferiority of DF-NBI versus CM-NBI in detecting superficial carcinoma in the pharynx and esophagus. DF-NBI appears to have a resolving power that, although significantly lower, is sufficient to achieve high diagnostic accuracy, comparable to that of CM-NBI.University Hospital Medical Information Network (UMIN, No. 000007585).

Early duodenal adenocarcinoma resembling a submucosal tumor cured with endoscopic resection: a case report

IntroductionPrimary adenocarcinomas resembling submucosal tumors are rare in the gastrointestinal tract. Almost all the submucosal tumor-like adenocarcinomas previously reported invaded the submucosa or deeper. Therefore, submucosal tumor-like lesions are usually treated by surgical resection, and those that arise in the duodenum have been treated by pancreaticoduodenectomy.Case presentationA 65-year-old Japanese man was diagnosed with a submucosal tumor-like adenocarcinoma in his duodenum. We considered it possible that the tumor invasion was limited to the mucosal or submucosal layers and could be removed by endoscopic resection. Tumor histopathology revealed a well-differentiated adenocarcinoma confined to the muscularis mucosae with no lymphovascular invasion. Complete resection of the carcinoma was achieved and there has been no recurrence three years after endoscopic resection.ConclusionsWe suggest that submucosal tumor-like adenocarcinomas arising in nonampullary duodenal sites should be diagnosed carefully with a view to possible endoscopic resection.