Yuichi Morohoshi

Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients

OBJECTIVE: The clinical significance of cytomegalovirus (CMV) reactivation complicating ulcerative colitis (UC) patients has been uncertain. It has therefore remained undetermined whether or not CMV reactivation should be treated in UC patients under immunosuppression. The aim of the study was to clarify the natural history of CMV reactivation in UC patients.METHODS: Sixty-nine UC patients with moderate to severe activity were enrolled in the study. All of the patients were treated with prednisolone, and/or immunosuppressants such as cyclosporine A. We sequentially monitored CMV reactivation every 2 wk up until 8 wk using the CMV antigenemia (Ag) assay and plasma quantitative real-time polymerase chain reaction (PCR) assay for CMV.RESULTS: Immunoglobulin (Ig) G for CMV was positive in 48 patients (69.6%) and negative in 21 patients (30.4%). CMV was reactivated in 25 patients out of the 48 seropositive patients (52.1%) during the study period. The CMV Ag and PCR values were low and none of the patients showed any evidence of CMV infection on biopsy specimens by hematoxylin and eosin staining. While gancylovir (GCV) was not used except in two patients, clinical outcomes including rates of remission and colectomy were not significantly different among the CMV reactivation-positive, -negative, and CMV IgG negative groups. Furthermore, CMV disappeared without GCV in most of the CMV reactivation-positive patients.CONCLUSIONS: CMV is frequently reactivated in active UC patients; however, it disappears without antiviral agents. Therefore, antiviral therapies should not be necessary for most UC patients with only CMV reactivation as long as CMV Ag values are low.

Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis

BackgroundNeutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction. However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate the contribution of NE by measuring NE activity in plasma and colonic mucosal tissue from UC patients and a murine acute colitis model, and to elucidate the therapeutic effect of the NE-specific inhibitor ONO-5046.MethodsThe NE enzyme activities in plasma and colonic mucosal tissue from UC patients were directly measured using an enzyme–substrate reaction. Acute colitis was induced in mice by administration of 1.5% dextran sulfate sodium (DSS) for 5 days. DSS-induced colitis mice were then treated with ONO-5046 (50 mg/kg body weight) intraperitoneally twice a day.ResultsIn UC patients, the NE enzyme activity was significantly elevated in both the plasma and colonic mucosal tissue compared with healthy controls. In DSS-induced colitis mice, the NE enzyme activity increased in parallel with the disease development. ONO-5046 showed therapeutic effects in DSS-treated mice by significantly reducing weight loss and histological score. ONO-5046 suppressed the NE enzyme activities in both plasma and culture supernatant of colonic mucosa from DSS-induced colitis mice.ConclusionsONO-5046, a specific NE inhibitor, prevented the development of DSS-induced colitis in mice. NE therefore represents a promising target for the treatment of UC patients.

A pilot open-labeled prospective randomized study between weekly and intensive treatment of granulocyte and monocyte adsorption apheresis for active ulcerative colitis

Background. Recently, granulocyte and monocyte adsorption apheresis (GMA) has been shown to be effective for active ulcerative colitis (UC). Its original weekly treatment schedule is effective in about 70% of active UC. However, it takes about 3–4 weeks to achieve remission, and the efficacy of a more frequent treatment schedule has not been elucidated yet. We performed a pilot open-labeled prospective, randomized, controlled study comparing weekly and an intensive treatment schedule with three treatment sessions per week in the first 2 weeks. Methods. Thirty active UC patients with moderate disease activity were prospectively and randomly assigned to receive the original or the intensive treatment schedule for a total of ten sessions. The proportion of the patients achieving remission and the time to achieve remission among them was compared between the two groups. The incidences of adverse effects were also compared between the two groups. Results. The rate of inducing remission in the original and intensive treatment group was 66.7% and 80%, respectively (P = 0.25, NS). The time to achieve remission was 27.2 days in the original group and 10.7 days in the intensive group (P = 0.04). Adverse effects were observed in two patients in each groups (NS). Conclusions. Intensive treatment with GMA is an efficacious and safe treatment for active UC. Because it induces rapid remission, it may be a more ideal treatment regimen than the conventional weekly treatment.

NOVEL TECHNIQUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN EXTERNAL GRASPING FORCEPS FOR SUPERFICIAL GASTRIC NEOPLASIA

Endoscopic submucosal dissection (ESD) for early stage gastric cancer (EGC) has improved the success rate of en bloc resection but results in perforation more often than does endoscopic mucosal resection. We report a novel technique of ESD using an external grasping forceps. A total of 265 lesions with EGC or gastric adenoma were enrolled in this study. Sixteen lesions were located in the upper third portion of the stomach, 114 in the middle third portion, and 135 in the lower third portion. After submucosal injection followed by circumcision of the lesions with a flex knife, the external grasping forceps was introduced with the help of a second grasping forceps and anchored at the margin of the lesion. Oral traction applied with this forceps could elevate the lesion and make the submucosal layer wider and more visible, thereby facilitating dissection of the submucosal layer under direct vision. The mean lesion size was 15.0 mm (range: 5–50 mm). All but 11 lesions (95.8%) could be resected en bloc with free margins. Mean procedure time was 45 min (range: 20–180 min). It was difficult to carry out this procedure when the lesions were located in the cardia, lesser curvature, or posterior wall of the upper third of the gastric body. Bleeding after ESD occurred in 10 patients (3.8%) and perforation occurred in one patient (0.4%). The endoscopic submucosal dissection using an external grasping forceps for superficial gastric neoplasia is efficacious and safe.

Recognition of and recent issues in hereditary diffuse gastric cancer

In East Asian countries, gastric cancer incidence is high, but detection rates for germline CDH1 mutations that cause hereditary diffuse gastric cancers (HDGCs) are low. Consequently, screens and genetic testing for HDGC are often considered unimportant. Since the first germline truncating CDH1 mutations in Japanese patients were reported, some HDGC cases have been reported, and some of these involve large germline rearrangements and de novo mutation of CDH1. New methods for mutation detection—such as multiplex ligation-dependent probe amplification, array comparative genomic hybridization, and exome sequencing—have become available, as have new experimental models, including novel gene-knockout mice and gastric organoids. Because of these advances, searches for candidate genes (e.g., CTNNA1, MAP3K6) and our understanding of HDGC pathogenesis have improved in recent years; moreover, there have been substantial changes in the field since the current HDGC consensus guidelines were released. This review focuses on recent issues and advances in the study of HDGC. For example, lobular breast cancer cases and de novo occurrences of DGC are unlikely to meet the existing criteria for genetic testing, but current evidence indicates that some such cases may be good candidates for genetic testing. It is important to recognize that HDGC is a syndrome and that lobular breast cancer can be the first manifestation of this syndrome. CDH1 testing, including analyses of large genomic rearrangements, should be recommended even in countries where few HDGC cases have been reported.

Intermittent Granulocyte and Monocyte Apheresis Versus Mercaptopurine for Maintaining Remission of Ulcerative Colitis: A Pilot Study

The effect of granulocyte and monocyte adsorption apheresis (GMA) on prevention of relapse of ulcerative colitis (UC) is not clear. This was a pilot open‐labeled, prospective, randomized, unblinded study to compare the tolerability and efficacy of intermittent GMA (once every 2 weeks) with mercaptopurine to maintain remission of UC. Twenty‐one patients with UC, who had achieved remission by induction therapies were randomly assigned to receive either intermittent GMA (N = 10) or oral mercaptopurine (0.5 mg/kg per day; N = 11). The study period was 24 months. The rate of the patients maintaining remission and the incidences of adverse effects were compared between the two groups. At 24 months, seven of 10 patients (70.0%) on intermittent GMA and seven of 11 patients (63.6%, P = 1.00) on oral mercaptopurine were still in remission. Three patients relapsed in each group. One patient taking mercaptopurine, but none receiving intermittent GMA, dropped out because of adverse effects. Intermittent therapy with GMA was well tolerated and a substantial proportion of patients maintained remission. Intermittent GMA therapy in maintaining remission of UC merits further investigation.

Effectiveness and clinical results of endoscopic management of sigmoid volvulus using unsedated water-immersion colonoscopy

Although intestinal obstruction as a result of sigmoid volvulus (SV) may be successfully resolved using endoscopic detorsion, surgical treatment remains the main therapeutic strategy. We evaluated the endoscopic detorsion procedure using unsedated water‐immersion colonoscopy for the treatment of SV.

A case of acute hepatitis B related to previous gynecological surgery in Japan

A 41-year-old woman became ill with acute hepatitis B after gynecological surgery performed by a surgeon who was hepatitis B surface antigen positive. The surgeon was positive for hepatitis B e antigen, and HBV DNA concentrations in the serum, saliva, and sweat of the surgeon were very high. HBV genotype and partial HBV DNA sequences from the HBV-infected surgeon were identical to those in the HBV-infected patient. Extensive research by the committee including infection control and prevention specialists judged the source of infection to be a surgeon infected with HBV. Transmission of HBV from a healthcare worker to patients who are not immune to HBV can actually happen. This case report illustrates the importance of a stringent policy of a nationwide HBV universal vaccination program.