Dye solution optimizing staining conditions for in vivo endocytoscopy for normal villi and superficial epithelial tumors in the duodenum.

BACKGROUND: Vital staining is mandatory for endocytoscopy, which enables visualization of gastrointestinal mucosa at the cellular level. This study aimed to identify a dye solution that would optimize staining conditions for in vivo endocytoscopy in the duodenum, including normal villi and superficial non-ampullary duodenal epithelial tumors (SNADETs). METHODS: We performed endocytoscopy in 9 patients who had normal villi (27 sites) and 20 patients with SNADETs (20 sites). The normal sites were allocated to methylene blue (MB; 5/2.5/1%), toluidine blue (TB; 1/0.5/0.25%), and crystal violet (1/0.5/0.25%) staining. Based on the results of normal sites, we used 1% MB or 0.5% TB for staining SNADETs. Three reviewers, including endoscopists and pathologists, evaluated and scored the endocytoscopy images (1, poor; 2, moderate; 3, good) for general image quality and visibility of structure and nuclei. We calculated frequencies and compared the proportions of the highest score of 3 (good). RESULTS: The majority of scores of 3 for normal villi was given to 0.5% TB (81%), followed by 1% MB. For SNADETs, 1% MB showed significantly higher scores compared with 0.5% TB (P=0.035). CONCLUSION: Among the dye solutions evaluated, 0.5% TB and 1% MB achieved the optimizing staining conditions for in vivo endocytoscopy for normal villi and SNADETs, respectively.

Simplified criteria for diagnosing superficial esophageal squamous neoplasms using Narrow Band Imaging magnifying endoscopy.

AIM: To simplify the diagnostic criteria for superficial esophageal squamous cell carcinoma (SESCC) on Narrow Band Imaging combined with magnifying endoscopy (NBI-ME). METHODS: This study was based on the post-hoc analysis of a randomized controlled trial. We performed NBI-ME for 147 patients with present or a history of squamous cell carcinoma in the head and neck, or esophagus between January 2009 and June 2011. Two expert endoscopists detected 89 lesions that were suspicious for SESCC lesions, which had been prospectively evaluated for the following 6 NBI-ME findings in real time: "intervascular background coloration"; "proliferation of intrapapillary capillary loops (IPCL)"; and "dilation", "tortuosity", "change in caliber", and "various shapes (VS)" of IPCLs (i.e., Inoue's tetrad criteria). The histologic examination of specimens was defined as the gold standard for diagnosis. A stepwise logistic regression analysis was used to identify candidates for the simplified criteria from among the 6 NBI-ME findings for diagnosing SESCCs. We evaluated diagnostic performance of the simplified criteria compared with that of Inoue's criteria. RESULTS: Fifty-four lesions (65%) were histologically diagnosed as SESCCs and the others as low-grade intraepithelial neoplasia or inflammation. In the univariate analysis, proliferation, tortuosity, change in caliber, and VS were significantly associated with SESCC (P < 0.01). The combination of VS and proliferation was statistically extracted from the 6 NBI-ME findings by using the stepwise logistic regression model. We defined the combination of VS and proliferation as simplified dyad criteria for SESCC. The areas under the curve of the simplified dyad criteria and Inoue's tetrad criteria were 0.70 and 0.73, respectively. No significant difference was shown between them. The sensitivity, specificity, and accuracy of diagnosis for SESCC were 77.8%, 57.1%, 69.7% and 51.9%, 80.0%, 62.9% for the simplified dyad criteria and Inoue's tetrad criteria, respectively. CONCLUSION: The combination of proliferation and VS may serve as simplified criteria for the diagnosis of SESCC using NBI-ME.

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).

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.

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

INTRODUCTION: Primary 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 PRESENTATION: A 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. CONCLUSIONS: We suggest that submucosal tumor-like adenocarcinomas arising in nonampullary duodenal sites should be diagnosed carefully with a view to possible endoscopic resection.

Bacteremia and endotoxemia after endoscopic submucosal dissection for gastric neoplasia: pilot study.

BACKGROUND: Because the invasive procedure of endoscopic submucosal dissection (ESD) entails a large mucosal defect which is left open, with extensive submucosal exposure to the indigenous bacterial flora, the procedure may have a substantial risk for bacteremia. Our aim was to examine gastric ESD-related bacteremia and endotoxemia in gastric neoplasia patients. METHODS: In patients who underwent ESD for superficial gastric neoplasia, blood cultures and plasma endotoxin measurements were done before, immediately after, and on day 2 after ESD. Clinically manifest infections and inflammatory markers, including C-reactive protein (CRP) and white blood cells, were monitored. RESULTS: Fifty patients (aged 69 ± 8 years; mean ± SD) were enrolled. The diameter of the resected specimens was 38 ± 18 mm and the procedure time of ESD was 66 ± 53 min. Two percent (2/100) of blood cultures after ESD were positive, with findings as follows: Propionibacterium species immediately after ESD, and Enterobacter aerogenes on day 2 after ESD, but no clinically manifest infection was observed. In 30% of the enrolled patients, CRP on day 2 after ESD had increased to levels higher than 1.0 mg/l. Plasma endotoxin levels, immediately after and on day 2 after ESD were correlated with CRP levels on day 2 after ESD. CONCLUSIONS: In spite of the invasive procedure with massive submucosal exposure to the indigenous bacterial flora, gastric ESD has a low risk for bacteremia. Gastric ESD-related endotoxemia may be linked to inflammatory reactions such as those shown by the increase of CRP or fever observed after ESD.

Diagnostic utility of narrow-band imaging endoscopy for pharyngeal superficial carcinoma.

AIM: To investigate the endoscopic features of pharyngeal superficial carcinoma and evaluate the utility of narrow-band imaging (NBI) for this disease. METHODS: In the present prospective study, 335 patients underwent conventional white light (CWL) endoscopy and non-magnified/magnified NBI endoscopy, followed by an endoscopic biopsy, for 445 superficial lesions in the oropharynx and hypopharynx. The macroscopic appearance of superficial lesions was categorized as either elevated (< 5 mm in height), flat, or depressed (not ulcerous). Superficial carcinoma (SC) was defined as a superficial lesion showing high-grade dysplasia or squamous cell carcinoma on histology. The color, delineation, and macroscopic appearances of the lesions were evaluated by CWL endoscopy. The ratio of the brownish area/intervascular brownish epithelium (IBE), as well as microvascular proliferation, dilation, and irregularities, was determined by non-magnified/magnified NBI endoscopy. An experienced pathologist who was unaware of the endoscopic findings made the histological diagnoses. By comparing endoscopic findings with histology, we determined the endoscopic features of SC and evaluated the diagnostic utility of NBI. RESULTS: The 445 lesions were divided histologically into two groups: a non-SC group, including non-neoplasia and low-grade dysplasia cases, and an SC group. Of the 445 lesions examined, 333 were classified as non-SC and 112 were classified as SC. There were no significant differences in age, gender, or the location of the lesions between the patients in the two groups. The mean diameter of the SC lesions was significantly greater than that of non-SC lesions (11.0 ± 7.6 mm vs 4.6 ± 3.6 mm, respectively, P < 0.001). Comparisons of CWL endoscopy findings for SC and non-SC lesions by univariate analysis revealed that the incidence of redness (72% vs 41%, respectively, P < 0.001) and a flat or depressed type of lesion (58% vs 44%, respectively, P = 0.013) was significantly higher in the SC group. Using non-magnified NBI endoscopy, the incidence of a brownish area was significantly higher for SC lesions (79% vs 57%, respectively, P < 0.001). On magnified NBI endoscopy, the incidence of IBE (68% vs 33%, P < 0.001) and microvascular proliferation (82% vs 51%, P < 0.001), dilation (90% vs 76%, P = 0.002), and irregularity (82% vs 31%, P < 0.001) was also significantly higher for the SC compared with the non-SC lesions. Multivariate analysis revealed that the incidence of redness (P = 0.022) on CWL endoscopy and IBE (P < 0.001) and microvascular irregularities (P < 0.001) on magnified NBI endoscopy was significantly higher in SC than non-SC lesions. Redness alone exhibited significantly higher sensitivity and significantly lower specificity for the diagnosis of SC compared with redness plus IBE and microvascular irregularities (72% vs 52%, P = 0.002; and 59% vs 92%, P < 0.001, respectively). The accuracy of redness plus IBE and irregularities for the diagnosis of SC was significantly greater than using redness alone (82% vs 62%, respectively, P < 0.001). CONCLUSION: Redness, IBE, and microvascular irregularities appear to be closely related to SC lesions. Magnified NBI endoscopy may increase the diagnostic accuracy of CWL endoscopy for SC.

Clinical impact of narrow-band imaging magnifying endoscopy for 'basal layer type squamous cell carcinoma' in the esophagus.

A 61-year-old man had received endoscopic submucosal dissection (ESD) for early gastric cancer twice. Then he had undergone annual control esophagogastroduodenoscopy using narrow-band imaging (NBI) magnifying endoscope. At the esophagogastroduodenoscopy, we were not able to detect any significant finding in the esophagus by conventional endoscopy. Switching to NBI mode, a brownish area was showed in the middle esophagus. The lesion showing the brownish area was predicted to be mucosal squamous cell carcinoma (SCC) as a result of assessment of morphologic change of intraepithelial papillary capillary loop under magnifying NBI observation. Lugol chromoendoscopy displayed the lesion as unstained area corresponding to the brownish area visualized by NBI. The ESD was performed for the lesion. Histology from ESD specimen showed SCC with minimal invasion to lamina propria at multifocal sites. The SCC was surrounded by low-grade intraepithelial neoplasia. Most of the SCC showed a high degree of cytological and architectural atypia confined to the lower half of the epithelium. The type of SCC was called as 'basal layer type SCC' mainly by Japanese pathologists. We suggest that magnifying NBI endoscopy can be useful for detecting and diagnosing 'basal layer type SCC'.

Endoscopic features of nonampullary duodenal tumors with narrow-band imaging.

BACKGROUND/AIMS: Endoscopic features of nonampullary duodenal adenomas and early adenocarcinomas are not well known. The aims of this study were to investigate the endoscopic features of the tumors using conventional endoscopy and narrow-band imaging magnified endoscopy, and to reveal the relationship between the endoscopic features and histological grades. METHODOLOGY: The study included 24 nonampullary duodenal adenomas and early adenocarcinomas in 22 patients who underwent conventional endoscopy and narrow-band imaging magnified endoscopy. The tumors were divided into histological groups according to the modified Vienna classification system. RESULTS: The 24 tumors were 17 adenomas and 7 carcinomas in situ, and divided into 10 Category 3 and 14 Category 4 lesions. On conventional endoscopy, 22 of the 24 (92%) lesions, had a milk-white mucosa and the frequency of a marginal-type one was significantly higher for the Category 4 group (p = 0.028). On narrow-band imaging magnified endoscopy, all tumors had a heterogeneous pattern. The frequency of an obscure mucosal pattern and a network microvascular pattern was significantly higher for the Category 4 group (p = 0.024 and 0.001, respectively). CONCLUSIONS: Narrow-band imaging magnified endoscopy following conventional endoscopy might be a promising approach to realizing lesions or predicting histological grade of nonampullary duodenal intraepithelial tumors.

Magnifying endoscopy with narrow-band imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study.

BACKGROUND: Conventional, white-light imaging endoscopy (WLE) results in a significant number of misdiagnoses in early gastric cancer. Magnifying endoscopy combined with narrow-band imaging (ME-NBI) is more accurate in the diagnosis of gastric cancer when the diagnostic triad of the disappearance of fine mucosal structure, microvascular dilation, and heterogeneity is used. OBJECTIVE: The aim of the present study was to evaluate the superiority of ME-NBI in the differential diagnosis of superficial gastric lesions identified with conventional WLE. DESIGN: Prospective, comparative study. SETTING: Single academic center. PATIENTS: This study involved patients who underwent WLE and ME-NBI for surveying synchronous or metachronous cancers because they had a high risk of gastric cancer. INTERVENTION: Patients with superficial gastric lesions that were diagnosed by WLE as cancer or non-cancer with a slight suspicion of cancer were prospectively enrolled in the study. ME-NBI was used to further characterize lesions picked up with WLE. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity for the diagnosis of gastric cancer, with pathology as the criterion standard. RESULTS: A total of 201 lesions (mean diameter [+/- SD] 7.0 +/- 4.0 mm) from 111 patients (98 men, 13 women; mean age 66.3 years) were evaluated. Fourteen of the 201 lesions were pathologically proven as gastric cancer; the others were noncancerous lesions. The sensitivity and specificity for ME-NBI diagnosis with the use of the triad (92.9% and 94.7%, respectively) were significantly better than for WLE (42.9% and 61.0%, respectively; P < .0001). LIMITATIONS: Single center and a highly selected population at high risk for gastric cancer. CONCLUSION: ME-NBI achieved superior accuracy in the differential diagnosis of superficial gastric lesions identified with WLE. Thus, ME-NBI may increase the diagnostic value of endoscopy in a population at high risk of gastric cancer.

Trimodal imaging endoscopy may improve diagnostic accuracy of early gastric neoplasia: a feasibility study.

BACKGROUND: A considerable number of superficial gastric neoplasias are overlooked with conventional white light imaging (WLI) endoscopy. OBJECTIVE: The aim was to investigate the diagnostic potential of trimodal imaging endoscopy (TME), which combines WLI, autofluorescence imaging (AFI), and narrow-band imaging (NBI), for superficial gastric neoplasia. DESIGN: Feasibility study. SETTING: Single academic center. PATIENTS: Sixty-two patients with or without gastric neoplasia. INTERVENTION: Each patient serially assessed with WLI, AFI, and magnifying endoscopy with NBI (ME-NBI) by an endoscopist blinded for clinical information. ME-NBI over WLI and AFI was designated as TME. Histopathology of biopsy and ESD specimens was evaluated and used as the gold standard. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity of endoscopic diagnosis of pathology-proven neoplasia by per-patient and per-lesion analyses. RESULTS: The study included 47 pathology-proven neoplasias and 44 pathology-proven nonneoplasias that were detected as neoplasias with any of the modalities. By a per-lesion analysis, the sensitivity of TME (89.4%) was higher than that of WLI (76.6%) and AFI (68.1%). The specificity of TME (98.0%) was higher than that of WLI (84.3%) and AFI (23.5%). By a per-patient analysis, the sensitivity of TME (90.9%) was higher than that of WLI (75%) and AFI (68.2%). The specificity of TME (100%) was higher than that of WLI (72.2%) and AFI (44.4%). LIMITATIONS: Case-enriched population at a single center. CONCLUSIONS: Higher diagnostic accuracy of TME over conventional WLI indicates the feasibility of TME for the efficacious diagnosis of early gastric neoplasia.

Ultrathin endoscopy versus high-resolution endoscopy for diagnosing superficial gastric neoplasia.

BACKGROUND: Ultrathin endoscopy (UTE) is an acceptable and cost-effective alternative to EGD with the patient under sedation, although the diagnostic accuracy of UTE is not well established. OBJECTIVE: To compare the diagnostic accuracy of UTE and high-resolution endoscopy (HRE) for superficial gastric neoplasia. DESIGN: Prospective comparative study. SETTING: Academic center. PATIENTS AND INTERVENTIONS: Patients with or without superficial gastric neoplasia underwent peroral UTE and HRE, back-to-back in a random order while under standard sedation. The procedures were performed by 2 endoscopists who were blinded to the clinical information. MAIN OUTCOME MEASUREMENTS: The rate of missed lesions and misdiagnosis, sensitivity, and specificity for the diagnosis of gastric neoplasia when using pathology as the reference standard. RESULTS: In total, 126 lesions (41 superficial gastric neoplasias, 85 nonneoplastic lesions) were recorded in 57 enrolled patients. For the diagnosis of gastric neoplasia, the sensitivity of UTE (58.5%) was significantly (P = .021) lower than that of HRE (78%), and the specificity of UTE (91.8%) was significantly (P = .014) lower than that of HRE (100%). The rate of missed lesions and misdiagnosis of gastric neoplasias when using UTE (41.5%) was significantly (P > .001) higher than that of HRE (22.0%). The corresponding rate of neoplasias at the proximal portion (fornix and corpus) when using UTE (29%) was significantly (P = .002) higher than that of HRE (7.2%), although the rates of neoplasias at the distal portion (angulus and antrum) were comparable for UTE and HRE. LIMITATION: Small sample numbers in an enriched population. CONCLUSIONS: The diagnostic accuracy of UTE is significantly lower than that of HRE for superficial gastric neoplasia, and this difference is particularly striking for neoplasias in the proximal stomach. For UTE to be used as an alternative modality, improvements in optical quality and the incorporation of additional procedures, including close-range observations and chromoendoscopy, are required to enhance visualization.

Self-regulating hyperthermia induced using thermosensitive ferromagnetic material with a low Curie temperature.

Hyperthermia has been used for many years to treat a variety of malignant tumors. The Curie temperature (Tc) is a transition point at which magnetic materials lose their magnetic properties, causing a cessation of current and thus heat production. The Tc enables automatic temperature control throughout a tumor as a result of the self-regulating nature of the thermosensitive material. We have developed a method of magnetically-induced hyperthermia using thermosensitive ferromagnetic particles (FMPs) with low Tc (43 degrees C), enough to mediate automatic temperature control. B16 melanoma cells were subcutaneously injected into the backs of C57BL/6 mice, after which tumors were allowed to grow to 5 mm in diameter. FMPs were then injected into the tumors, and the mice were divided into three groups: group I (no hyperthermia, control); group II (one hyperthermia treatment); and group III (hyperthermia twice a week for 4 weeks). When exposed to a magnetic field, the FMPs showed a sharp rise in heat production, reaching the Tc in tissue within 7 min, after which the tissue temperature stabilized at approximately the Tc. In groups I and II, all mice died within 30-45 days. In group III, however, 6 of 10 mice remained alive 120 days after beginning treatment. Our findings suggest that repeated treatment with magnetically-induced self-regulating hyperthermia, mediated by FMPs with a low Tc, is an effective means of suppressing melanoma growth. A key advantage of this hyperthermia system is that it is minimally invasive, requiring only a single injection for repeated treatments with automatic temperature control.

Noninvasive temperature measurement method for hyperthermia treatment using ferromagnetic implant with low curie temperature.

Induction heating using 'ferromagnetic implant with low Curie temperature (FILCT)' is one of the heating methods for hyperthermia. However, a lot of energy is needed to heat malignant tumors; the heating efficiency has to be improved. In order to address this problem, we propose using FILCT as a probe for temperature. A non-invasive temperature measurement system was developed based on this approach. A key advantage of this system is that it can noninvasively distinguish whether the temperature of FILCT has reached the Curie temperature or not. As a result, materials with high heating efficiency may be used.

Imaging of epithelial cancer in sub-terahertz electromagnetic wave.

We used sub-terahertz (THz) imaging to exam two cross sections of epithelial cancer tissue embedded in paraffin using a 0.19 THz electromagnetic wave. The sub-THz imaging system was constructed with a tunnel injection transit time (TUNNETT) diode, a Schottky barrier diode detector and a X-Z stage. We examined the difference between a sub-THz wave absorption in melanoma and nevus tissue.