Tomohiko R. Ohya

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.

Rebleeding rate after interventional therapy directed by capsule endoscopy in patients with obscure gastrointestinal bleeding

BackgroundThe precise role of capsule endoscopy in the diagnostic algorithm of obscure gastrointestinal bleeding has yet to be determined. Despite the higher diagnostic yield of capsule endoscopy, the actual impact on clinical outcome remains poorly defined. The aim of this study was to evaluate the follow-up results of patients with obscure gastrointestinal bleeding to determine which management strategies after capsule endoscopy reduced rebleeding.MethodsAll patients in whom the cause of obscure gastrointestinal bleeding was investigated between May 2004 and March 2007 were studied retrospectively. We evaluated the clinical outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy using the rebleeding rate as the primary outcome.ResultsSeventy-seven patients with obscure gastrointestinal bleeding underwent capsule endoscopy. Capsule endoscopy identified clinically significant findings that were thought to be the sources of obscure gastrointestinal bleeding in 58.4% of the patients. The overall rebleeding rate was 36.4%. The rebleeding rate was significantly higher among patients with insignificant findings than among those with significant findings (p = 0.036). Among the patients in whom capsule endoscopy produced significant findings, the rebleeding rate of the patients who underwent therapeutic interventions was significantly lower than that in those who did not undergo intervention (9.5% vs 40.0%, p = 0.046).ConclusionFollow-up and further aggressive interventions are necessary for patients with obscure gastrointestinal bleeding and significant capsule endoscopy findings to reduce the chance of rebleeding.

Chemically assisted submucosal injection facilitates endoscopic submucosal dissection of gastric neoplasms

BACKGROUND AND STUDY AIMS A randomized in vivo animal study previously demonstrated that topical injection of mesna solution (sodium-2-mercaptoethanesulfonate) chemically softened submucosal connective tissues and facilitated mechanical dissection of the submucosal tissue plane. The present study evaluated the technical feasibility and safety of chemically assisted endoscopic submucosal dissection (CA-ESD) using mesna in 20 consecutive patients who underwent endoscopic excision of gastric neoplasm. MATERIALS AND METHODS Following the margination of the lesion with a mucosal circumcision, 4 - 12 mL of 10 % mesna solution was injected into the submucosal layer. Mechanical submucosal dissection was then performed by bluntly cleaving the chemically treated submucosal layer with the tip of a cap-fitted gastroscope. The use of cautery was restricted to prophylactic hemostasis, dissection of the coagulated vessels and persistent submucosal tissues, and the final snare resection. Post-therapeutic ulceration repair and adverse events were followed up during a 1-week hospitalization and by repeat endoscopies at 1 day, 1 week, and 1 month after the procedure. RESULTS Sixteen gastric cancers and four adenomas were treated in this study. The sampled tissue measured 38.25 +/- 14.53 mm, with an en bloc resection rate of 100 %. Mean operation time was 21.17 +/- 11.6 minutes. The time spent using cautery was limited to 26.1 % of the total submucosal dissection time. Ulcerations healed normally without complications. CONCLUSIONS This preliminary study demonstrates that submucosal injection of mesna facilitates and expedites mechanical submucosal dissection. The major limitations in this study include the single-arm study design and a small patient population.

Endoscopic features of colorectal serrated lesions using image-enhanced endoscopy with pathological analysis.

Objective To clarify of the features of sessile serrated adenoma/polyp (SSA/P) observed with image-enhanced endoscopy using immunohistochemical staining. Materials and methods Twenty-five hyperplastic polyps (HP) and 46 SSA/P were studied with autofluorescence imaging (AFI) and magnifying endoscopy with narrow-band imaging (ME-NBI). AFI color change, capillary dilatation, existence of a mucous layer on the tumor surface, and pit dilatation under ME-NBI were examined retrospectively. Immunohistochemical staining was performed with the proliferation-associated antigen MIB-1 (Ki-67). Results Using AFI, a magenta color was observed in 32% of HP and 44% of SSA/P. With NBI observation, capillary dilatation was observed in 4% of HP and 11% of SSA/P, a mucous cap was observed in 60% of HP and 94% of SSA/P, and pit dilatation was observed in 28% of HP and 80% of SSA/P. When magenta color, capillary dilatation, mucous cap, and pit dilatation were used for the differential diagnosis of SSA/P from HP, the sensitivity, specificity, and accuracy were 43, 68, and 52% for AFI, respectively, 10, 96, and, 41% for capillary dilatation, respectively, 94, 40, and 75% for mucous cap, respectively, and 80, 72, and 78% for pit dilatation, respectively. Compared with HP, MIB-1-positive cells were more frequently distributed in the gland’s intermediate zone in SSA/P. Conclusion The biological malignant potential of SSA/P could be higher compared with HP as suggested by the MIB-1 stain. Therefore, endoscopic differentiation of SSA/P from HP is important, and the findings of a mucous cap and dilatated pit might be helpful for the differentiation of SSA/P from HP.

Imaging by Magnifying Endoscopy with NBI Implicates the Remnant Capillary Network As an Indication for Endoscopic Resection in Early Colon Cancer

Introduction. This study examined whether magnifying endoscopy with NBI observation (ME-NBI) could be useful selecting the appropriate treatment for submucosal invasive cancer (SM cancer). Patients and Methods. We analyzed 515 cases of colon tumors excised endoscopically or surgically. We classified capillary network pattern into four types according to the degree of dilatation, irregularity, and distribution of microcapillary features. Results. The comparison of capillary pattern and histological features revealed microcapillary networks by using confocal laser-scanning microscopy and ME-NBI in intramucosal lesion or SM cancer with remnant neoplastic glands at the superficial layer. In contrast, the network was absent in SM cancer with desmoplastic reactions, which invaded deeper into the submucosal layer. Conclusions. The remaining microcapillary network is designed to maintain the architecture of neoplastic glands. Consequently, loss of this network could correlate with depth of tumor invasion and desmoplastic reaction. Therefore, we can decide the appropriate treatment by using ME-NBI method.

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.).

In Vivo Imaging of Enteric Neuronal Networks in Humans Using Confocal Laser Endomicroscopy

Neurons and glia comprise the enteric nervous system (ENS), which is an essential part of the gut. Changes of the enteric glia cell function are associated with functional diseases and motility disorders.1 The neurons of the ENS are collected into 2 types of ganglia: myenteric (Auerbach’s) and submucosal (Meissner’s) plexuses. Myenteric plexuses are located between the inner and outer layers of the muscularis externa, and submucosal plexuses are located in the submucosal layer.1 Thus, direct, in vivo imaging of the ENS in humans is not possible with conventional white light endoscopy. Confocal laser endomicroscopy (CLE) is a new established endoscopic method providing in vivo histology at subcellular resolution during ongoing endoscopy.2 Preceding porcine model studies demonstrated that use of CLE at levels of the submucosa or superficial muscularis might enable the ENS to be visualized in vivo.3,4 Two ypes of endomicroscopic systems are available. Probeased endomicroscopy (Mauna Kea Technologies, Paris, okyo, France) allows real-time cellular imaging with igh frame rates at a distinct depth,5 whereas embedded ype of endomicroscopy (Pentax, Tokyo, Japan) allows ndomicroscopy with high-resolution and variable imagng plane depth (0 –250 m).6 Endomicroscopy requires contrast agents for fluorescence imaging. Commonly used dyes are fluorescein and Acriflavine. The aim of the current study was to evaluate, whether and how endomicroscopy might be able to visualize the enteric nervous system of the submucosal layer of the colon in humans.

A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers

AIM To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection (ESD) gastric ulcers. METHODS Patients with gastric tumors indicated for ESD were prospectively studied. After ESD, all patients were treated with intravenous omeprazole for the first 3 d. Patients were then randomly assigned to oral lafutidine or rabeprazole. Ulcer size, ulcer size reduction rate, and ulcer stage were evaluated 4 wk later. Occurrence of complication was monitored throughout the 4-wk period. RESULTS Sixty five patients were enrolled in the study, and 60 patients were subjected to the final analysis. In the lafutidine group (30 lesions in 29 patients), initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm, respectively. In the rabeprazole group (34 lesions in 31 patients), the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm, respectively. Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%, respectively (P = 0.974). Ulcer stage 4 wk post-ESD did not differ significantly between the two groups (P = 0.868). Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period, although the difference of bleeding rate between the two groups was not statistically significant (P = 0.157). CONCLUSION Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.

Visualization of colorectal neoplasia by a second-generation autofluorescence imaging system.

Abstract Objective. Autofluorescence imaging (AFI) systems may allow better visualization of colorectal neoplasia than conventional methods. However, this is difficult to demonstrate objectively. Recently, a second-generation AFI system with a noise-reduction algorithm was developed. We aimed to objectively evaluate the visualization of colorectal neoplasia by using a second-generation AFI system and software to calculate the color-contrast index. Material and methods. We retrospectively reviewed 53 consecutive colorectal neoplasias examined using the second-generation AFI system. Color-contrast indices between the colorectal lesions and the surrounding normal mucosa in the WLI, AFI and NBI images were calculated. The WLI, AFI, NBI and CE images were also evaluated by endoscopists using questionnaire-based visualization scores. Results. The color-contrast index seen in the AFI images (33.74 ± 9.20) was significantly higher than that in either the WLI (11.14 ± 6.14) or NBI images (11.72 ± 7.12). There was no significant difference between the color-contrast indices of the WLI and NBI images. The mean AFI image visualization score (6.7 ± 1.8) was significantly higher than that of WLI (6.0 ± 1.7), and tended to be higher than that of the NBI images (6.1 ± 1.6) when assessed by less-experienced endoscopists. Conclusions. This study objectively demonstrates that compared to WLI and NBI, the second-generation AFI system enables superior visualization of colorectal neoplasms. The visualization scores were higher for the AFI images when evaluated by less-experienced endoscopists. These results indicate that the second-generation AFI system may aid less-experienced endoscopists in the detection of colorectal neoplasia.

Computer-aided diagnosis of neoplastic colorectal lesions using 'real-time' numerical color analysis during autofluorescence endoscopy.

Objective Differentiating non-neoplastic colorectal lesions from neoplastic lesions during screening colonoscopies is essential to reduce the unnecessary treatment of non-neoplastic lesions. The present study was conducted to verify the diagnostic yields of the computer-aided diagnostic system that enables ‘real-time’ color analysis of colorectal lesions when applied to autofluorescence endoscopy (AFE). Patients and methods Consecutive patients who were scheduled to undergo a therapeutic colonoscopy in our department were enrolled in this study. The encountered lesions were evaluated in AFE and color-tone sampling was performed. Lesions with green/red (G/R) ratios less than 1.01 were judged to be neoplastic and those with G/R ratios of at least 1.01 were considered to be non-neoplastic. All lesions greater than 5 mm were endoscopically removed and lesions less than 5 mm were biopsied. Results During the study period, a total of 32 patients with 102 colorectal lesions were evaluated with AFE. The mean G/R ratio for all neoplastic lesions was 0.86 [95% confidence interval (CI), 0.63–1.01], which was significantly lower than the mean G/R ratio for non-neoplastic lesions (1.12; 95% CI, 0.98–1.26; P<0.001). The mean G/R ratios were 1.36 (95% CI, 1.21–1.57) in normal mucosa, 1.12 (95% CI, 0.98–1.26) in hyperplastic lesions, 0.88 (95% CI, 0.69–1.02) in adenomas, and 0.61 (95% CI, 0.54–0.73) in intramucosal cancers. A G/R ratio cutoff value of 1.01 was applied for discriminating between neoplastic lesions and non-neoplastic lesions, and yielded sensitivity, specificity, positive and negative predictive values of 94.2, 88.9, 95.6, and 85.2%, respectively. Conclusion This diagnostic tool may lead to the reduction of unnecessary treatments for non-neoplastic lesions.