ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUBMUCOSAL INVASIVE GASTRIC CANCER AND CURABILITY CRITERIA

Aims: The aims of the present study were to evaluate the feasibility of endoscopic submucosal dissection (ESD) as curative treatment for node‐negative submucosal invasive early gastric cancer (EGC) and to consider further expansion of the curability criteria for submucosal invasive EGC. Methods: A total of 977 EGC in 855 patients treated by ESD were enrolled. They were divided into intramucosal cancer (M); minimally submucosal invasive cancer (<500 µm from the muscularis mucosa) (SM1); and deeper submucosal invasive cancer (>500 µm from the muscularis mucosa) (SM2). The technical feasibility of ESD for SM1 and M were compared, and the clinical prognosis of SM1 was evaluated. Furthermore, the volume of carcinoma invading to the submucosal layer, which we called the SM volume index, was calculated virtually to analyze its correlation with lymphatic‐vascular invasion. Results: There were no statistical differences in technical outcomes and complications between M and SM1. Curative resection rates were significantly better in M than in SM1 (M, 92.6%; SM1, 63.8%). No local recurrences and distant metastases were found in 48 SM1 patients declared to have undergone curative resections. Most cases (72.0%) with successful ESD but non‐curative resection exceeded 30 mm in maximum size, and no local recurrences and metastases were found in these patients. The SM volume index of these cases was comparatively small. Conclusion: The technical and theoretical validity of ESD for SM1 was validated. The possibility of further expansion of the curability criteria for submucosal invasive cancers was suggested by the evaluation of the SM volume index.     

Efficacy of magnifying endoscopy with flexible spectral imaging color enhancement in the diagnosis of colorectal tumors

Background

Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is an image-enhanced endoscopy that captures the surface and vascular patterns of colorectal tumors. We evaluated and compared FICE magnification to narrow-band imaging (NBI) magnification.

Methods

Flexible spectral imaging color enhancement or NBI magnification was performed to the visualize surface and vascular patterns of colorectal tumors, classified into 4 types: Type A, Type B, Type C1/C2, and Type C3, as previously reported. A total of 235 colorectal tumors were examined. The correlations between classifications found by FICE or NBI magnification and histopathological diagnoses were examined. Image evaluation was validated by assessing inter-observer and intra-observer agreements on examinations.

Results

Twenty-eight hyperplastic polyps (HPs), 115 tubular adenomas (TAs), 72 mucosal and slightly invaded submucosal cancers (M-sSM), and 20 massively invaded submucosal cancers (mSM) were diagnosed. By FICE magnification, HP and TA were observed in 93.3 and 6.7% of Type A (15 lesions), respectively. TA, M-sSM, and HP were observed in 82.6, 15.4, and 2.0% of Type B (52 lesions), respectively. M-sSM, TA, and mSM were observed in 50.0, 46.0, and 4.0% of Type C1/2 (50 lesions), respectively. mSMs were observed in all 7 Type C3 lesions. In diagnosing mSM in Type C3, the sensitivity and specificity of FICE magnification were 77.7 and 100%, respectively, compared to those of NBI, at 63.6 and 99.0%, respectively. Imaging evaluation was validated accurately by intra- and intra-observer measurements showing consistent results.

Conclusions

The classification of colorectal tumors by FICE magnification correlated well with the histopathological diagnoses, similar to findings for NBI magnification. FICE magnification can be evaluated accurately with the same diagnostic classifications as those used for NBI magnification.     

Impaired regulation of serum hepcidin during phlebotomy in patients with chronic hepatitis C

Aim: This study was conducted to determine the clinical relevance of hepcidin, a recently identified key iron regulatory hormone, in patients with chronic hepatitis C virus (C‐HCV). Methods: Serum hepcidin levels were measured in 9 C‐HCV patients by surface‐enhanced laser desorption/ionization time of flight mass spectrometry (SELDI‐TOF‐MS), and compared to those of healthy controls. Sequential changes of hepcidin were also investigated during phlebotomy. Results: Serum hepcidin and ferritin were significantly higher in C‐HCV than in controls (P = 0.0002), these two variables were strongly related to each other (r = 0.658; P < 0.01), and phlebotomy significantly decreased serum hepcidin in C‐HCV (P = 0.0007); all these results recollect the hepcidin response to iron signal. Hepcidin/ferritin ratio, an index of the appropriateness of hepcidin expression relative to iron overload, was significantly lower in C‐HCV than in controls (0.33 ± 0.41 vs. 0.73 ± 0.36, P = 0.0068). This relative impairment of hepcidin expression was not reversible after phlebotomy (P = NS). Conclusions: Although the hepcidin expression responds to iron conditions in C‐HCV, this response is relatively limited. This relative impairment of hepcidin expression may be relevant to disease progression, and thus correction of its regulation may be beneficial for these iron‐overloaded C‐HCV patients.     

Endoscopic submucosal dissection for colorectal lesions

Endoscopic submucosal dissection (ESD) has been developed to overcome limitations of conventional endoscopic resection techniques. By using ESD, curative treatment can be reliably confirmed by histopathologic examination of the specimen that was resected completely in an en bloc fashion. Data published by Japanese experts suggest that colorectal ESD is both effective and safe when performed by experts. ESD can achieve reliable complete resection even for large and difficult lesions that were entirely impossible to resect by conventional endoscopic mucosal resection technique. However, colorectal ESD is more difficult than gastric and esophageal ESD so that it is necessary to have specific devices and treatment strategy. Because the balance between the risk and benefit is always very important, appropriate training is necessary before starting to perform colorectal ESD.     

Fcγ receptor expression on hepatic macrophages and histological activity of chronic hepatitis

Abstract: Aims/Background: Activated liver macrophages in chronic hepatitis express a high affinity receptor for IgG named FcγRI. This study was performed to find the difference in FcγRI expression between chronic hepatitis B (CHB) and C (CHC) with reference to histological activity. Methods: Consecutive patients with CHB (20 cases) and CHC (25 cases) were enrolled in the study. Inflammatory activity was evaluated using the modified histological activity index (HAI). FcγRI-positive macrophages were quantitatively measured by computer assisted morphometry. Results: Total HAI score was significantly higher in CHB than in CHC. Confluent necrosis was observed in significantly higher frequency in CHB at Stages 3–5 than in CHC. The percentage area of FcγRI-positive macrophages was significantly higher in CHB than in CHC. In CHB, the percentage area of FcγRI-positive macrophages correlated with total HAI (< 0.01) as well as the degree of confluent necrosis (< 0.01), interface hepatitis (< 0.05) and portal inflammation (< 0.05). FcγRI-positive macrophages accumulated mainly at the site of confluent necrosis. In CHC, no correlation was observed between activated macrophages and any histological categories. Conclusion: These results suggest that FcγRI-positive macrophages are associated with confluent necrosis in CHB, which is more common in CHB patients than in CHC.     

Possibility of ex vivo animal training model for colorectal endoscopic submucosal dissection

Purpose

Colorectal endoscopic submucosal dissection (ESD) has not been standardized due to technical difficulties and requires extensive training for reliability. Ex vivo animal model is convenient, but has no blood flow. The objective of this study is to evaluate the characteristics of various ex vivo animal models including a blood flow model for colorectal ESD training and the usefulness of practicing endoscopic hemostasis and closure using an animal model.

Methods

Harvested porcine cecum, rectum, and stomach and bovine cecum and rectum were analyzed regarding ease of mucosal injection, degree of submucosal elevation, and status of the proper muscle layer. Ex vivo animal model with blood flow was made using the bovine cecum. The vessel around the cecum was detached, and red ink was injected. Endoscopic hemostasis for perioperative hemorrhage and endoscopic closure for perforation were performed in this model.

Results

Mucosal injection was easily performed in the bovine cecum and rectum. Submucosal elevation was low in the bovine cecum, while the proper muscle layer was not tight in the porcine rectum and bovine cecum. Endoscopic hemostasis were accomplished in six (60 %) out of ten procedures of the ex vivo blood flow model. In two non-experts, the completion rates of endoscopic closure were 40 and 60 % in the first five procedures. These rates became 100 % in the last five procedures.

Conclusions

We have evaluated the characteristics of various ex vivo animal models and shown the possibility of training for endoscopic hemostasis and endoscopic closure in the ex vivo animal model.     

Endoscopic diagnosis of small intestinal diseases

The technological development in endoscopy is directed toward improved accuracy of the diagnoses of novel diseases. The capsule endoscope and balloon-assisted endoscope are examples of such technological development. By these novel technologies, the small intestine can be examined in more detail. Therefore, an increasing number of novel diseases have been discovered, requiring the establishment of diagnosis and treatment strategies for these unknown diseases. In particular, obscure gastrointestinal bleeding, Crohn’s disease, and nonsteroidal anti-inflammatory drug-induced enteropathy are of great interest to endoscopists. The capsule endoscope is the best method for screening the small intestine; however, the development of supporting methods such as the patency capsule is eagerly desired.     

In situ expression of Granzyme B and Fas‐ligand in the liver of viral hepatitis

Abstract: Background/Aims: The molecular mechanism involved in hepatocellular injury in viral hepatitis remains to be clarified. Methods: We investigated the in situ expression of effector molecules of cytotoxic T lymphocytes such as Fas‐ligand (Fas‐L), perforin and Granzyme B (Gr‐B) immunohistochemically in liver tissues from 20 patients with chronic hepatitis B (CHB) and C (CHC). The degree of cell infiltration was analysed semi‐quantitatively and compared with the histological activity index (HAI). Fas‐L was expressed in both CD4 and CD8 T‐cells in the portal tract as well as in the parenchyma. Results: Immunostaining of serial sections demonstrated that mononuclear cells at interface hepatitis and focal necrosis were mainly Fas‐L positive CD8 T‐cells. On the other hand, the expression of perforin or Gr‐B was limited to a few mononuclear cells in the portal tract and parenchyma. Semi‐quantitative analysis showed a positive correlation between HAI and the grade of infiltration of CD8 T‐cells or Fas‐L‐positive cells, while the correlation was not apparent between HAI and the number of Gr‐B positive cells. The expression of these molecules was not different between types of viruses. Conclusions: These results suggest that Fas‐L‐positive CD8 T‐cells play a major role in the pathogenesis of liver cell injury in chronic hepatitis.