Tetsuji Fujinaga

Integrated diagnostic strategy for the invasion depth of early gastric cancer by conventional endoscopy and EUS

BACKGROUND Although conventional endoscopy (CE) and EUS are considered useful for predicting the invasion depth (T-staging) in early gastric cancer (EGC), no effective diagnostic strategy has been established. OBJECTIVE To produce simple CE criteria and to elucidate an efficient diagnostic method by combining CE and EUS for accurate T-staging. DESIGN Single-center retrospective analysis. SETTING Academic university hospital. PATIENTS Consecutive patients with EGC from April 2007 to March 2012 who underwent CE and EUS before treatment. INTERVENTIONS Recorded endoscopic images were independently reviewed by 3 observers. The CE criteria for massive invasion were defined, and their utility and the additional value of EUS were assessed. MAIN OUTCOME MEASUREMENTS The accuracy of CE based on the criteria and the accuracy of EUS. RESULTS Two hundred thirty patients were enrolled: 195 with mucosal cancer or cancer in the submucosa less than 500 μm from the muscularis mucosae and 35 with invasive cancers. Multivariate analysis of the CE findings by 1 observer revealed that an irregular surface and a submucosal tumor-like marginal elevation were significantly associated with massive invasion. The simple CE criteria, consisting of those 2 features, had an overall accuracy of 73% to 82% and no significant differences in the diagnostic yield compared with EUS in all observers. CE accurately revealed mucosal cancer, and EUS efficiently salvaged the lesions that were over-diagnosed by CE. With our strategy, which involved the CE criteria and the optimal use of EUS, the comprehensive accuracy exceeded 85% in each observer. LIMITATIONS Retrospective, single-center study. CONCLUSIONS We demonstrated a practical strategy for T-staging in EGC using simple CE criteria and EUS.

The effectiveness of an anti-human IL-6 receptor monoclonal antibody combined with chemotherapy to target colon cancer stem-like cells

Recent studies have demonstrated that cancer stem cells (CSCs) can initiate and sustain tumor growth and exhibit resistance to clinical cytotoxic therapies. Therefore, CSCs represent the main target of anticancer therapy. Interleukin-6 (IL-6) promotes cellular proliferation and drug resistance in colorectal cancer, and its serum levels correlate with patient survival. Therefore, IL-6 and its downstream signaling molecule the signal transducer and activator of transcription-3 (STAT3) represent potential molecular targets. In the present study, we investigated the effects of IL-6 and its downstream signaling components on stem cell biology, particularly the chemoresistance of CSCs, to explore potential molecular targets for cancer therapy. The colon cancer cell line WiDr was cultured in serum-free, non-adherent, and three-dimensional spheroid-forming conditions to enrich the stem cell-like population. Spheroid-forming cells slowly proliferated and expressed high levels of Oct-4, Klf4, Bmi-1, Lgr5, IL-6, and Notch 3 compared with adherent cells. Treatment with an anti-human IL-6 receptor monoclonal antibody reduced spheroid formation, stem cell-related gene expression, and 5-fluorouracil (5-FU) resistance. In addition, IL-6 treatment enhanced the levels of p-STAT3 (Tyr705), the expression of Oct-4, Klf4, Lgr5, and Notch 3, and chemoresistance to 5-FU. siRNA targeting Notch 3 suppressed spheroid formation, Oct-4 and Lgr5 expression, and 5-FU chemoresistance, whereas STAT3 inhibition enhanced Oct-4, Klf4, Lgr5, and Notch 3 expression and 5-FU chemoresistance along with reduced spheroid growth. Taken together, these results indicate that IL-6 functions in dichotomous pathways involving Notch 3 induction and STAT3 activation. The former pathway is involved in cancer stem-like cell biology and enhanced chemoresistance, and the latter pathway leads to accelerated proliferation and reduced chemoresistance. Thus, an anti-human IL-6 receptor monoclonal antibody or Notch 3 inhibition may be superior to STAT3 inhibition for CSC-targeting therapies concomitant with anticancer drugs.

Esophageal adenocarcinoma with white opaque substance observed by magnifying endoscopy with narrow band imaging.

White opaque substance (WOS) is observed in the gastric neoplasia of 0‐IIa type using magnifying endoscopy with narrow band imaging (NBI‐ME). Colonic and duodenal neoplasms with WOS have also been reported. Immunohistochemical examination with adipophilin reveals WOS in gastric neoplasms as lipid droplets, and WOS is specific for neoplasm with intestinal or gastrointestinal phenotype. We herein report a case of adenocarcinoma of the esophagogastric junction with WOS. A male patient in his sixties was found by esophagogastroduodenoscopy to have an esophageal elevated lesion. NBI‐ME showed whitish deposits that looked similar to WOS in gastric neoplasms. The patient underwent endoscopic submucosal dissection and the lesion was resected in a single piece. This tumor had diffuse positivity for adipophilin and gastrointestinal phenotype.

Localized gastric amyloidosis mimicking a submucosal tumor-like gastric cancer

Commentary Even with the advent of the proton pump inhibitor and improvements in medical management, peptic ulcer disease remains an important clinical problem. The relative frequency of various adverse events occurs at a rate of approximately 1% to 2% per ulcer patient per year of follow-up. The most serious adverse events of peptic ulcer disease include hemorrhage, perforation, penetration, and gastric outlet obstruction. In contrast to perforating ulcer, penetrating ulcer erodes into another organ instead of the peritoneal cavity. There are reported cases of gastric ulcers penetrated into the pancreas, spleen, gastrohepatic omentum, biliary tract, liver, greater omentum, mesocolon, colon, pericardium, and vascular structures. Based on a recent guideline from the American Society for Gastrointestinal Endoscopy, endoscopy does not have a therapeutic role in the management of penetrating gastric ulcers. When a penetrating ulcer is diagnosed, it is important to quickly seek surgical consultation.

Adenoma of colorectal laterally spreading tumor nongranular type with biological phenotypic features similar to cancer: Colorectal laterally spreading tumor

Colorectal laterally spreading tumors (LSTs) are morphologically subdivided into granular (LST‐G) and nongranular (LST‐NG) categories. We aimed to elucidate the differences in oncogenic characteristics between the two types.

Evaluation of endoscopic entire 3D image acquisition of the digestive tract using a stereo endoscope

Because the view angle of the endoscope is narrow, it is difficult to get the whole image of the digestive tract at once. If there are more than two lesions in the digestive tract, it is hard to understand the 3D positional relationship among the lesions. Virtual endoscopy using CT is a present standard method to get the whole view of the digestive tract. Because the virtual endoscopy is designed to detect the irregularity of the surface, it cannot detect lesions that lack irregularity including early cancer. In this study, we propose a method of endoscopic entire 3D image acquisition of the digestive tract using a stereo endoscope. The method is as follows: 1) capture sequential images of the digestive tract by moving the endoscope, 2) reconstruct 3D surface pattern for each frame by stereo images, 3) estimate the position of the endoscope by image analysis, 4) reconstitute the entire image of the digestive tract by combining the 3D surface pattern. To confirm the validity of this method, we experimented with a straight tube inside of which circles were allocated at equal distance of 20 mm. We captured sequential images and the reconstituted image of the tube revealed that the distance between each circle was 20.2 ± 0.3 mm (n=7). The results suggest that this method of endoscopic entire 3D image acquisition may help us understand 3D positional relationship among the lesions such as early esophageal cancer that cannot be detected by virtual endoscopy using CT.

Evaluation of motion compensation method for assessing the gastrointestinal motility using three dimensional endoscope

Functional gastrointestinal disorders (FGID) are the most common gastrointestinal disorders. The term ”functional” is generally applied to disorders where there are no structural abnormalities. Gastrointestinal dysmotility is one of the several mechanisms that have been proposed for the pathogenesis of FGID and is usually examined by manometry, a pressure test. There have been no attempts to examine the gastrointestinal dysmotility by endoscopy. We have proposed an imaging system for the assessment of gastric motility using a three-dimensional endoscope. After we newly developed a threedimensional endoscope and constructed a wave simulated model, we established a method of extracting three-dimensional contraction waves derived from a three-dimensional profile of the wave simulated model obtained with the endoscope. In the study, the endoscope and the wave simulated model were fixed to the ground. However, in a clinical setting, it is hard for endoscopists to keep the endoscope still. Moreover, stomach moves under the influence of breathing. Thus, three-dimensional registration of the position between the endoscope and the gastric wall is necessary for the accurate assessment of gastrointestinal motility. In this paper, we propose a motion compensation method using three-dimensional scene flow. The scene flow of the feature point calculated by obtained images in a time series enables the three-dimensional registration of the position between the endoscope and the gastric wall. We confirmed the validity of a proposed method first by a known-movement object and then by a wave simulated model.