Masamitsu Nakao

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms.

AIM To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The en block resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

Prospective study of the evaluation of the usefulness of tumor typing by narrow band imaging for the differential diagnosis of gastric adenoma and well-differentiated adenocarcinoma.

Background and Aim:  Presently, the differential diagnosis of gastric adenoma and well‐differentiated adenocarcinoma by endoscopy is very difficult. We carried out magnifying endoscopy with narrow band imaging (NBI) in lesions that required discrimination between gastric adenoma and well‐differentiated adenocarcinoma, and prospectively evaluated whether the tumor typing that we propose is useful for their differential diagnosis.

Usefulness of the DL in ME with NBI for determining the expanded area of early-stage differentiated gastric carcinoma

AIM To investigate whether magnifying endoscopy with narrow band imaging (ME-NBI) is useful for evaluating the area of superficial, depressed- or flat-type differentiated adenocarcinoma of the stomach. METHODS This procedure was performed in Saitama Medical University International Medical Center, Japanese Red Cross Kumamoto Hospital and Kitakyushu Municipal Medical Center. The subjects were 31 patients in whom biopsy findings, from superficial, depressed- or flat-type gastric lesion, suggested differentiated adenocarcinoma in the above 3 hospitals between January and December 2009. Biopsy was performed on the lesion and non-lesion sides of a boundary (imaginary boundary) visualized on ME-NBI. The results were pathologically investigated. We evaluated the accuracy of estimating a demarcation line (DL) on ME-NBI in comparison with biopsy findings as a gold standard. RESULTS The DL that could be recognized at 2 points on the orifice and anal sides of each lesion during ME-NBI was consistent with the pathological findings in 22 patients with 0-IIc lesions, 7 with 0-IIb lesions, and 2 with 0-IIb + IIc lesions, showing an accuracy of 100%. CONCLUSION The results suggest the usefulness of ME-NBI for evaluating the area of superficial, depressed- and flat-type differentiated adenocarcinoma of the stomach.

Gastrointestinal: Gastric mucosa-associated lymphoma presented with unique vascular features on magnified endoscopy combined with narrow-band imaging

Gastric lymphoma arising from mucosal associated lymphoid tissue (MALT) has distinct clinical and histological characteristics compared with nodal B-cell lymphoma. Magnified endoscopy (ME) combined with narrow band imaging (NBI) is widely used and the usefulness is well recognized for the diagnosis of gastritis and gastric cancer. However, there has been no report on ME combined with NBI for gastric MALT lymphoma, despite the necessity of differentiating it from gastric cancer. We report a case ofgastricMALTlymphomainwhichMEcombinedwithNBIcould detectuniquevascularfeaturesdifferentfromthoseseenincircumscribed atrophic gastritis or poorly differentiated adenocarcinoma. A 66-year-old woman underwent endoscopic screening of the upper gastrointestinal tract revealed ill-defined, brownish, superficial depressed lesion in the anterior wall of the upper gastric body (Fig. 1). ME combined with NBI system, consisting of an image processor (CV-260SL, Olympus Medical Systems, Tokyo, Japan), a light source (CLV-260SL), and a zoom endoscope (GIF-Q240Z) showed the disappearance of the surface structure and the appearance of abnormal blood vessels.Abnormal vessels were defined as new vessels that were not seen in the adjacent mucosa. They were large vessels like a tree trunk with long, bare branches that can be called as ‘tree like appearance’ (Fig. 2). Biopsy was taken from this abnormal portion and revealed hyperplasia of atypical centrocyte-like cells with small to medium-sized, ovoid nuclei and clear cytoplasm in the lamina propria mucosae and their infiltration among glandular epithelial cells, suggesting lymphoepithelial lesion. The atypical lymphocytes were immunohistochemically CD20+ ,C D10-, and CD5-. These findings were consistent with gastric MALT lymphoma. In this case report, we have shown that the tree-like appearance of the abnormal blood vessels, clearly observed by ME with NBI, could be one of the unique features suggestive of gastric MALT lymphoma. This finding could be helpful because superficial depressed type lesion potentially include circumscribed atrophic gastritis and poorly differentiated adenocarcinoma. Of note, these vascular findings are relatively easy to detect by using NBI, because NBI can present clearly defined vascular image. Therefore, our data also suggest the importance of NBI for the endoscopic evaluation of gastric MALTlymphoma.The combination of ME with NBI may also reduce the number of biopsy of gastric MALT lymphoma because it can provide precise information about the distribution of MALT lymphoma in the stomach.

A case of gastric mucosa-associated lymphoid tissue lymphoma in which magnified endoscopy with narrow band imaging was useful in the diagnosis

Recently, we reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma presenting with unique vascular features. In the report, we defined the tree-like appearance (TLA) on the images of abnormal blood vessels which resembled branches from the trunk of a tree in the shiny mucosa, in which the glandular structure was lost. The 67-year-old female was diagnosed with gastric MALT lymphoma. The patient received eradication therapy for H. pylori. Conventional endoscopy revealed multiple ill-delineated brownish depressions in the stomach and cobblestone-like mucosa was observed at the greater curvature to the posterior wall of the upper gastric body 7 mo after successful eradication. Unsuccessful treatment of gastric MALT lymphoma was suspected on conventional endoscopy. Conventional endoscopic observations found focal depressions and cobblestone-like appearance, and these lesions were subsequently observed using magnified endoscopy combined with narrow band imaging to identify abnormal vessels presenting with a TLA within the lesions. Ten biopsies were taken from the area where abnormal vessels were present within these lesions. Ten biopsies were also taken from the lesions without abnormal vessels as a control. A total of 20 biopsy samples were evaluated to determine whether the diagnosis of MALT lymphoma could be obtained histologically from each sample. A positive diagnosis was obtained in 8/10 TLA (+) sites and in 2/10 TLA(-) sites. Target biopsies of the site with abnormal blood vessels can potentially improve diagnostic accuracy of gastric MALT lymphoma.

Nationwide survey for acute liver failure and late-onset hepatic failure in Japan

BackgroundA nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan.MethodsTwo-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys.ResultsIn total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation).ConclusionAlthough the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years.

Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon-β injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy

To improve the therapeutic efficacy of sofosbuvir/ledipasvir (SOF/LDV) for the retreatment of patients after daclatasvir/asunaprevir (DCV/ASV), a customized therapy with or without lead‐in interferon (IFN)‐β injections was formulated according to the types of resistance‐associated substitutions (RAS) in the non‐structural protein (NS)5A region of genotype 1b hepatitis C virus (HCV).

Diagnosis of boundary in early gastric cancer.

Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique, which allowsresection of larger superficial tumors in the esophagus, stomach, and colon. Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD, because too much resection can potentially take more time and can induce a higher complication rate, while too little resection can result in a non-curative resection. The boundary diagnosis is often difficult for early gastric cancer, mainly because of the underlying condition of chronic gastritis. Due to recent developments in endoscopy, including magnified endoscopy and narrow band endoscopy, the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.

Serum asunaprevir concentrations showing correlation with the extent of liver fibrosis as a factor inducing liver injuries in patients with genotype-1b hepatitis C virus receiving daclatasvir plus asunaprevir therapy

Aims Liver injury can occur during antiviral therapies with direct-acting antivirals (DAAs), potentially necessitating discontinuation of the therapies, with consequent worsening of the sustained viral response (SVR) rates, in patients with hepatitis C virus (HCV). To clarify the mechanisms involved in serum transaminase level elevation, we performed a retrospective evaluation of the serum concentrations of daclatasvir and asunaprevir, both classified as DAAs, in patients receiving treatment with a combination of the two drugs. Methods Subjects were 278 Japanese patients with genotype-1b HCV who received daclatasvir plus asunaprevir therapy for more than 4 weeks. Serum concentrations of both the DAAs were measured at 4 weeks after the initiation of therapy. Result Liver injuries including serum AST and/or ALT level elevation to 150 U/L or over were found in 34 patients (12.2%). Multivariate logistic regression analysis identified serum asunaprevir concentrations as being significantly associated with developing liver injury, with an odds ratio of 1.046 (95% confidence interval 1.011–1.082, p<0.05). Serum asunaprevir concentrations showed correlation with the extent of liver fibrosis, estimated by peripheral platelets counts and serum albumin levels and baseline and FIB4 index and serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at 4 weeks of the therapy; the concentrations were significantly higher among patients showing 3.0 or more of M2BPGi levels than among those with the levels less than 3.0; on the other hand, no such correlation/difference was found in serum daclatasvir concentrations. Conclusion High serum concentrations of serum asunaprevir, which were associated with the extent of liver fibrosis, appear to provoke the occurrence of liver injury in patients with genotype-1b HCV receiving combined daclatasvir plus asunaprevir therapy.

A Case of Chronic Hepatitis Caused by Hepatitis C Virus Exhibiting a Discrepancy Between Serogroup and Genotype Because of Inter-Genotypic 2b/1b Recombination - A Pitfall in Antiviral Therapy with Direct-Acting Antivirals -

A 40‐year‐old male patient with virologic relapse after daclatasvir plus asunaprevir therapy for a serogroup 1 hepatitis C virus (HCV) infection visited our hospital for retreatment. Virologic examinations revealed that a genotype 2b HCV strain carrying both NS3‐S122N / D168A and NA5A‐R30Q / L31M / Q54H / Y93H mutations had relapsed. The patient received sofosbuvir plus ribavirin therapy, but virologic relapse occurred once again. Sequencing of the HCV genome clarified an intergenotypic recombination of 2b and 1b with an estimated crossover point between nucleotides 3114 and 3115, corresponding to the N‐terminal end of the NS3 region (DDBJ/EMBL/GenBank databases accession no. LC273304). The NS5B‐S282T mutation was not detected in the HCV strain, and resistance‐association substitutions in the NS3 and NS5A regions were similar to those at baseline. Direct sequencing of the core and NS4A regions corresponding to the targeting sites of genotyping and serogrouping, respectively, is useful to determine the combination of direct‐acting antivirals when a discrepancy is observed between the serogroup and genotype of HCV strains.