Masahiro Sakaguchi

Helicobacter pylori in Patients Receiving Long-Term Dialysis

Background:Helicobacter pylori (H. pylori) is considered to cause gastritis and gastric ulcer. In dialysis patients, digestive tract hemorrhage is sometimes fatal. However, in regard to H. pylori infection in patients with end-stage renal disease (ESRD), many issues remain to be clarified. Methods: This study included 76 symptom-free patients with ESRD. The subjects consisted of 25 patients with chronic renal failure who had not received dialysis and 51 patients receiving dialysis. On upper digestive tract endoscopy, specimens were taken for analysis of H. pylori. Urease test, culture, and microscopy were performed. Results: In non-dialysed patients, the prevalence of H. pylori-positive patients was 56.0%. In dialysed patients, the percentage was significantly lower (27.5%). In dialysed patients, the mean duration of dialysis was 8.1 ± 7.5 months (mean ± SD) in H. pylori-positive patients and 56.2 ± 60.9 months (mean ± SD) in H. pylori-negative patients (p < 0.001). 11 of 13 non-dialysed patients with chronic gastritis were positive for H. pylori. However, only 5 of 24 dialysed patients were positive for H. pylori infection. Conclusions: Long-term dialysis decreased the prevalence of H. pylori. The reduction of gastric acid secretion related to chronic gastritis may be involved.

Prevalence of Helicobacter pylori antibodies in long‐term dialysis patients

Background:  Helicobacter pylori has been reported to play an important role in the development of gastritis and gastric ulcer.

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271)

CD25 expression on residual leukemic blasts at the time of allogeneic hematopoietic stem cell transplant predicts relapse in patients with acute myeloid leukemia without complete remission

Abstract Recent studies have shown that CD25 expression at the time of diagnosis of acute myeloid leukemia (AML) may be associated with an unfavorable outcome. We focus on patients with AML without complete remission (CR) and examine the clinical correlation between surface CD25 expression at the time of transplant and subsequent transplant outcomes. We observed a significant difference in overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) between CD25 positive (+) (n = 22) and negative (−) groups (n = 44) (2-year OS; CD25 (+) group: 5% vs. CD25 (−) group: 40%, p < 0.0001, 2-year DFS; 5% vs. 29%, p < 0.0001, 2-year CIR; 77% vs. 52%, p = 0.03). Multivariate analysis showed that CD25 expression was an independent adverse factor for OS (p = 0.002) and relapse (p = 0.001). Patients with AML with residual CD25 positive blasts at the time of transplant may require additional therapy before or after transplant to improve survival.

A Case Report of Interferon β Monotherapy for High Hepatitis C Viral Load in Dialysis Patients

Abstract:  A 42‐year‐old male dialysis patient was infected with hepatitis C virus (HCV), and treated with interferon β (IFN‐β) for a rapid increase in viral load. After dialysis three times a week, 3 million units of IFN‐β were intravenously infused for 1 h. The treatment was markedly effective, and the virus was eliminated in the sixth week. Therapy was continued for 24 weeks, and HCV negativity has been maintained for more than 6 months after the completion of administration. The blood IFN level slowly decreased immediately after administration. The mean trough level was 37 U/mL, and the half‐life was 65 min. No adverse event requiring discontinuation of the treatment occurred, showing that IFN alone may safely eliminate the virus in dialysis patients with high hepatitis C viral load. Many dialysis patients are latently infected with HCV, and the infection affects the prognosis. Therefore, establishment of a therapeutic method is urgently needed.

Endoscopic retrograde cholangiopancreatography in paediatric patients with biliary disorders

Endoscopic retrograde cholangiopancreatography (ERCP) has long been used in children. The usefulness of ERCP in paediatric patients with various biliary disorders, however, has not been well documented. Thirty‐two sessions of ERCP performed in 29 paediatric patients ranging in age from 1 month to 15 years were evaluated. Endoscopic retrograde cholangiopancreatography was to confirm diagnosis or to obtain detailed information about their pancreaticobiliary system. Cannulation was successful in all patients. Opacification of the biliary tracts was also successful in all except for three patients with extrahepatic biliary atresia. Endoscopic retrograde cholangiopancreatography was assessed to be successful in making a differential diagnosis of neonatal hepatitis from extrahepatic biliary atresia, and in having a confirmed diagnosis of anomalous arrangement of the pancreaticobiliary ductal system associated with choledochal cyst. The procedure was also useful for obtaining detailed information on the pancreaticobiliary system in the other children. No accidents occurred during the endoscopic procedures in any of the paediatric patients. When a confirmed diagnosis or detailed information is needed in paediatric patients with biliary disorders, ERCP is a useful and safe technique.

Mycophenolate mofetil is effective only for involved skin in the treatment for steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Dear Editor, Recently, mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), has been used for acute graft-versus-host disease (aGVHD) prophylaxis and as a treatment for steroid-refractory aGVHD (SR-aGVHD) [1–4]. In the setting of treatment for SR-aGVHD, only a few studies [2–4] have analyzed the individual response in three involved organs (only skin, only liver, and only gut) in a small number of patients treated with MMF. No study has reported the response in two or more involved organs. We evaluated whether MMF is effective for one, two, or three involved organs in patients who had received MMF for SR-aGVHD. From 2004 to 2014, we identified 42 patients who received oral MMF for the treatment of SR-aGVHD (grade I, n = 7; grade II–IV, n = 35) (Supplemental Table 1). Transplant procedures have been described in detail elsewhere [5]. All patients received aGVHD prophylaxis with cyclosporine (CsA) or tacrolimus (FK) as well as short-term methotrexate. aGVHD, SRaGVHD, and responses to MMF were diagnosed and graded according to previously established criteria [2, 6]. MMF was orally administered at a median dose of 1333 mg/day (range 500–3000) in addition to standard CsA or FK with more than 1 mg/kg steroid. Twice the initial amount of MMF was administered when aGVHD had not improved or worsened after the initiation of MMF treatment. The median duration of MMF administration was 97 days (range 11–674 days). Four weeks after the initiation of MMF, 24 patients achieved complete response (CR), 4 had partial response (PR), and 14 patients had no response (NR). The response including all organs was comparable in related or unrelated donor transplantation, and in bone marrow transplantation or peripheral blood stem cell transplantation (Supplemental Fig. 1a, d). All three recipients from human leukocyte antigen (HLA)-haploidentical donors received conditioning with antithymocyte globulin, and the response was NR (Supplemental Fig. 1b, c). However, the response was similar in HLA matched and one mismatched donor transplantation (Supplemental Fig. 1b). Regarding the involved organs, the response rate in patients who developed only skin GVHD was higher than in those with only liver, only gut, skin and liver, liver and gut, skin and gut, or all three organs (92.3 vs. 0, 0, 20, 0, 37.5, 0 %, respectively, p < 0.001, Fig. 1a). The response in skin was similar to that in liver among patients who developed skin and liver SR-aGVHD (CR and PR rate 20 vs. 20 %, Fig. 1b). Moreover, the response in skin was similar to that in gut among patients who developed skin and gut SRaGVHD (CR rate 50 vs. 37.5 %, Fig. 1c). This study demonstrated that patients with only skin SRaGVHD responded to MMF better than those with only liver, only gut, skin and liver, or skin and gut aGVHD. Furthermore, the response rate in skin was low, similar to that in liver or gut Electronic supplementary material The online version of this article (doi:10.1007/s00277-016-2854-0) contains supplementary material, which is available to authorized users.

Occurrence of Donor Cell-derived Lymphoid Blast Crisis 24 Years Following Related Bone Marrow Transplantation for Chronic Myeloid Leukemia.

We herein report a unique case of donor cell leukemia (DCL), as donor cell-derived lymphoid blast crisis of chronic myeloid leukemia (CML) was observed 24 years after related bone marrow transplantation for CML in the chronic phase. Short tandem repeat testing of the leukemic blast sample revealed full donor chimerism, strongly indicative of DCL. The original donor is healthy with a normal complete blood cell count for the past 24 years. This rare case may provide a precious opportunity to consider not only the underlying mechanism of DCL, but also the pathogenesis of CML.

Characteristics of refractory gastroesophageal reflux disease (GERD) symptoms -is switching proton pump inhibitors based on the patient's CYP2C19 genotype an effective management strategy?

OBJECTIVE We investigated factors related to proton pump inhibitor (PPI) -refractory gastroesophageal reflux disease (GERD) symptoms, particularly with respect to acid, the CYP2C19 genotype and psychological aspects. METHODS Patients with an Frequency Scale for the Symptoms of GERD (FSSG) score of ≥8 after the initial treatment were switched to therapy with rabeprazole at a dose of 20 mg once daily for eight weeks. We investigated the rate of improvement in PPI-refractory GERD symptoms, background factors, the Hospital Anxiety and Depression Scale (HADS) score and the CYP2C19 genotype. Patients Sixty patients endoscopically diagnosed with reflux esophagitis within the past six months who had received omeprazole at a dose of 20 mg once daily for eight weeks or longer were enrolled. RESULTS In 71.6% of the patients, the FSSG score decreased to <8 after treatment with omeprazole at a dose of 20 mg once daily for ≥8 weeks, resulting in improvements in their GERD symptoms. Significant factors related to omeprazole-refractory GERD symptoms included a longer disease duration (p=0.0004) and higher HADS score (p=0.01). Among the omeprazole-refractory cases, only 23.5% of the patients showed symptom improvement after switching to rabeprazole. There were no significant differences in the average scores for FSSG (p=0.089) or HADS (p=0.182), before or after the drug change. A total of 92% of the rabeprazole poor responders were homo/hetero extensive metabolizers for the CYP2C19 genotype. CONCLUSION Our findings suggest that switching the PPI from omeprazole (20 mg once daily) to rabeprazole (20 mg once daily) is not a significant effective therapeutic strategy for improving PPI-refractory GERD symptoms, taking into consideration possible psychometric factors and patients who require stronger acid suppression than that achieved with a double dose of PPIs for PPI-refractory GERD symptoms.

Efficacy of Prophylactic Endoscopic Variceal Sclerotherapy in Patients with Hepatocellular Carcinoma

Abstract: A setrospective study to determine the influence of prophylactic endoscopic sclerotherapy on the survival rate of patients with hepatocellular carcinoma complicated by esophageal varices was conducted. The subjects included 132 patients without esophageal varices at the time of diagnosis (NV group), 37 patients with hepatocellular carcinoma for whom prophylactic sclerotherapy had been performed for risky esophageal varices (PS group) and 26 patients with hepatocellular carcinoma and risky varices for whom prophylaxis was not performed (NPS group). Multiple regression analysis was used to identify factors affecting the survival rate of the 132 patients without esophageal varices. A tumor embolus in the primary branch or main trunk of the portal vein adversely affected long‐term survival in these patients. The patients were further divided into 2 subgroups, namely those with (Vp3) and without (Vp0‐Vp2) tumor emboli in the main trunk and primary branch of the portal vein. In the Vp0– Vp2 emboli subgroup, the patients who received prophylactic sclerotherapy and the patients without varices had similar survival rates. Patients without prophylactic sclerotherapy had a significantly shorter survival rate than the group without varices and the prophylactic sclesotherapy group (p<0.01 and p<0.05). A significant bleeding rate was observed in the group without prophylaxis and not in the group with prophylaxis. However, in the Vp3 subgroup, the survival rate in each group was identical. Thus prophylactic variceal sclerotherapy is indicated for patients with hepatocellular carcinoma who do not have tumor emboli in the main trunk or primary branch of portal vein.