Publications by authors named "Jun Nakamura"

503 Publications

Effects of empagliflozin in different phases of diabetes mellitus-related cardiomyopathy: a prospective observational study.

BMC Cardiovasc Disord 2021 Apr 29;21(1):217. Epub 2021 Apr 29.

Department of Cardiology, Fujieda Municipal General Hospital, Surugadai 4-1-11, Fujieda, Shizuoka, 426-8677, Japan.

Background: Diabetes mellitus-related cardiomyopathy (DMCMP), defined as left ventricular (LV) dysfunction caused by hyperglycemia in the absence of coronary artery disease, leads to heart failure (HF). Previous studies have shown that treatment with sodium-glucose co-transporter 2 inhibitor (SGLT2i) reduces the risk of exacerbation of HF. The beneficial effects of SGLT2i on HF depend not only on indirect actions such as osmotic diuresis but also on direct actions on the myocardium, leading to improvements in LV function. However, it remains unclear whether SGLT2i treatment is equally effective in any phase of DMCMP. The aim of this observational study was to compare the efficacy of SGLT2i treatment on LV dysfunction between early and advanced DMCMP.

Methods: Thirty-five symptomatic non-ischemic HF patients with LV ejection fraction > 40% and type 2 diabetes mellitus (T2DM) treated with empagliflozin (EMPA group) and 20 controls treated without SGLT2i were enrolled. According to the myocardial extracellular volume fraction (ECV), a reliable marker of cardiac fibrosis quantified by cardiac magnetic resonance, the EMPA group was further divided into early DMCMP (n = 16, ECV ≤ 30%) and advanced DMCMP (n = 19, ECV > 30%) groups and followed up prospectively. Echocardiography was performed at baseline and after 12 months. LV function assessed as LV global longitudinal strain (LVGLS) and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e') were compared.

Results: ECV was strongly correlated with T2DM duration (r = 0.65, p < 0.001). At baseline, each group had a similar background. After 12 months, the EMPA group, especially the early DMCMP group, showed remarkable improvements in LVGLS (ΔLVGLS: 2.9 ± 3.0% (EMPA) vs. 0.6 ± 2.2% (controls), p = 0.005, and 4.6 ± 1.5% (early DMCMP) vs. 1.6 ± 3.3% (advanced DMCMP), p = 0.003) and E/e' (ΔE/e': - 1.5 ± 4.7 vs. - 0.3 ± 3.0, p = 0.253, and - 3.4 ± 5.5 vs. - 0.1 ± 3.5, p = 0.043).

Conclusions: The positive effects of empagliflozin on LV dysfunction were more remarkable in early than in advanced DMCMP. Early intervention of SGLT2i for DMCMP may be preferable.
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http://dx.doi.org/10.1186/s12872-021-02024-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086321PMC
April 2021

Localized gastric amyloidosis diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Clin J Gastroenterol 2021 Apr 22. Epub 2021 Apr 22.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

A 49-year-old man was found to have an elevated lesion on esophagogastroduodenoscopy (EGD) for gastric cancer screening. This lesion had been noted in EGD 13 years earlier, but the patient had not received EGD since then. Endoscopy showed a relatively soft subepithelial lesion (SEL) in the gastric antrum. In addition, endoscopic ultrasonography (EUS) showed a 20-mm-sized, slightly non-uniform hypoechoic mass in the submucosa. Since the diagnosis could not be confirmed by mucosal biopsy, EUS-guided fine-needle aspiration (EUS-FNA) was performed. Hematoxylin-eosin staining of EUS-FNA samples revealed deposition of acidophilic unstructured materials. The structure was positive on Congo red staining, and green polarized light was also observed under a polarizing microscope. Moreover, it was resistant to potassium permanganate reaction, negative for serum amyloid A protein, positive for anti-λ chain antibody, and negative for anti-κ chain, anti-amyloid A, anti-transthyretin, and anti-β2-microglobulin antibodies. Therefore, the lesion was diagnosed as AL-λ-type amyloidosis. No systemic amyloidosis findings were found; thus, the patient was finally diagnosed with localized gastric AL amyloidosis. If an SEL is seen without disease-specific endoscopic findings, amyloidosis should be included in the differential diagnosis, and EUS-FNA can contribute to obtaining tissue samples in such cases.
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http://dx.doi.org/10.1007/s12328-021-01416-4DOI Listing
April 2021

Risk of metastatic recurrence after endoscopic resection for esophageal squamous cell carcinoma invading into the muscularis mucosa or submucosa: a multicenter retrospective study.

J Gastroenterol 2021 Apr 21. Epub 2021 Apr 21.

National University Corporation Hirosaki University, Hirosaki, Japan.

Background: We aimed to elucidate the risk of metastatic recurrence after endoscopic resection (ER) without additional treatment for esophageal squamous cell carcinomas (ESCCs) with tumor invasion into the muscularis mucosa (pT1a-MM) or submucosa (T1b-SM).

Methods: We retrospectively enrolled patients with pT1a-MM/pT1b-SM ESCC after ER at 21 institutions in Japan between 2006 and 2017. We compared metastatic recurrence between patients with and without additional treatment, stratified into category A (pT1a-MM with negative lymphovascular invasion [LVI] and vertical margin [VM]), B (tumor invasion into the submucosa ≤ 200 µm [pT1b-SM1] with negative LVI and VM), and C (others). Subsequently, using multivariate Cox analysis, we evaluated risk factors for metastatic recurrence after ER without additional treatment.

Results: We enrolled 593 patients, and metastatic recurrence occurred in 38 patients. Metastatic recurrence after additional treatment was significantly lower than that after no additional treatment in category C (9.1% vs. 23.6% in 5 years, p = 0.001), whereas no significant difference was noted in categories A (0.0% vs. 2.6%) and B (0.0% vs. 4.3%). In patients without additional treatment after ER, risk factors for metastatic recurrence were lymphatic invasion (hazard ratio [HR], 5.61), positive VM (HR, 4.55), and tumor invasion into the submucosa > 200 μm (HR, 3.25), and, but near half of the patients with metastatic recurrence had no further recurrence after salvage treatment, resulting in excellent 5-year disease-specific survival in categories A (99.6%) and B (100.0%).

Conclusions: Closed follow-up with no additional treatment may be an acceptable option after ER in pT1a-MM/pT1b-SM1 ESCC with negative LVI and VM.
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http://dx.doi.org/10.1007/s00535-021-01787-yDOI Listing
April 2021

Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia With Proton Magnetic Resonance Spectroscopy Brain Glutamate Level: A Mega-analysis of Individual Participant-Level Data.

JAMA Psychiatry 2021 Apr 21. Epub 2021 Apr 21.

Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York.

Importance: Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.

Objective: To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.

Data Sources: The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.

Study Selection: In total, 45 1H-MRS studies contributed data.

Data Extraction And Synthesis: Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor.

Main Outcomes And Measures: Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL).

Results: In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P < .001; cerebrospinal fluid-corrected Glu, F1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.

Conclusions And Relevance: Findings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060889PMC
April 2021

A Pilot Randomized Crossover Trial of Wet Suction and Conventional Techniques of Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Upper Gastrointestinal Subepithelial Lesions.

Gastroenterol Res Pract 2021 22;2021:4913107. Epub 2021 Mar 22.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Methods: Twenty-six patients with UGI-SELs indicated for EUS-FNA were randomly assigned to the dry-first arm using the dry technique for the first two passes or the wet-first arm using the wet technique for the first two passes using a cross-over design with a ratio of 1 : 1. The primary endpoint was the cellularity score of the EUS-FNA specimens rated on a 4-point scale (0-3). The secondary endpoints were the factors influencing cellularity in each suction technique.

Results: The mean cellularity score was 1.65 ± 1.20 for the wet technique and 2.00 ± 0.98 for the dry technique ( = 0.068). Logistic regression analysis showed that higher cellularity may be related to the final diagnosis of gastrointestinal stromal tumors in the dry technique and the SEL location in the upper stomach in the wet technique.

Conclusion: The wet EUS-FNA technique failed to show a potential for improved cellularity of specimens compared to the dry technique for UGI-SELs.
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http://dx.doi.org/10.1155/2021/4913107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007354PMC
March 2021

Ca-ATPase Molecules as a Calcium-Sensitive Membrane-Endoskeleton of Sarcoplasmic Reticulum.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.

The Ca-transport ATPase of sarcoplasmic reticulum (SR) is an integral, transmembrane protein. It sequesters cytoplasmic calcium ions released from SR during muscle contraction, and causes muscle relaxation. Based on negative staining and transmission electron microscopy of SR vesicles isolated from rabbit skeletal muscle, we propose that the ATPase molecules might also be a calcium-sensitive membrane-endoskeleton. Under conditions when the ATPase molecules scarcely transport Ca, i.e., in the presence of ATP and ≤ 0.9 nM Ca, some of the ATPase particles on the SR vesicle surface gathered to form tetramers. The tetramers crystallized into a cylindrical helical array in some vesicles and probably resulted in the elongated protrusion that extended from some round SRs. As the Ca concentration increased to 0.2 µM, i.e., under conditions when the transporter molecules fully carry out their activities, the ATPase crystal arrays disappeared, but the SR protrusions remained. In the absence of ATP, almost all of the SR vesicles were round and no crystal arrays were evident, independent of the calcium concentration. This suggests that ATP induced crystallization at low Ca concentrations. From the observed morphological changes, the role of the proposed ATPase membrane-endoskeleton is discussed in the context of calcium regulation during muscle contraction.
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http://dx.doi.org/10.3390/ijms22052624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961605PMC
March 2021

Disappearance of Gastric Hyperplastic Polyps after the Discontinuation of Proton Pump Inhibitor in a Patient with Liver Cirrhosis.

Case Rep Gastroenterol 2021 Jan-Apr;15(1):202-209. Epub 2021 Feb 18.

Department of Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan.

Here, we report on a rare case of gastric hyperplastic polyps which disappeared after the discontinuation of proton pump inhibitor (PPI). The patient was an 83-year-old woman with liver cirrhosis and portal hypertension, along with gastroesophageal reflux disease treated by PPI. An initial upper gastrointestinal endoscopy showed unique polypoid lesions in the greater curvature of the stomach. Biopsy specimens of the lesions were diagnosed as hyperplastic polyps and she was followed. One year later, a second endoscopy showed that the lesions had increased in number and size, and an endoscopic mucosal resection (EMR) was performed for the main polyps. The resected specimens indicated a proliferation of foveolar epithelium cells with an increase of capillary ectasia and parietal cell hyperplasia, which was thought to be induced by hypergastrinemia from the PPI. Three months after the EMR, she was admitted because of bleeding from the remaining polyps along with an increase in new polyps. After conservative treatment, PPI was stopped and rebamipide was used. One year and 6 months later, an endoscopy showed the complete disappearance of all gastric polyps.
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http://dx.doi.org/10.1159/000511885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989726PMC
February 2021

Painful Left Bundle Branch Block Syndrome Complicated by Iron-Overload Cardiomyopathy.

Intern Med 2021 Mar 22. Epub 2021 Mar 22.

Department of Cardiology, Fujieda Municipal General Hospital, Japan.

Painful left bundle branch block (LBBB) syndrome is a rare disease that presents as simultaneous chest pain and transient LBBB without myocardial ischemia. We diagnosed a 72-year-old Japanese man with painful LBBB syndrome complicated by iron-overload cardiomyopathy. Phlebotomy was initially performed to improve myocardial iron deposition and conductive disturbance. Ironically, his chest pain was fully improved by the completion of incessant LBBB and walk-through phenomenon. However, this case demonstrates a clinically significant therapeutic strategy for cardiomyopathy-induced painful LBBB syndrome. Due to the lack of treatment guidelines, individualized treatment is required for each case of painful LBBB.
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http://dx.doi.org/10.2169/internalmedicine.7052-21DOI Listing
March 2021

A simple method for diagnosing gallbladder malignant tumors with subserosa invasion by endoscopic ultrasonography.

BMC Cancer 2021 Mar 17;21(1):288. Epub 2021 Mar 17.

Department of Gastroenterology, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Background: If the depth of gallbladder malignant tumor (GBMT) invasion is deeper than the subserosa (ss), cholecystectomy is insufficient. In past reports that used endoscopic ultrasonography (EUS) to diagnose the depth of tumor invasion, it was difficult to diagnose GMBT invasion in the ss without a narrow or disrupted lateral hyperechoic layer (LHEL). Therefore, we developed a simple preoperative method to diagnose GBMTs with ss invasion.

Methods: Forty-nine GBMT patients who underwent both EUS and surgery were enrolled: 15 patients whose tumors invaded the mucosa (m) or muscularis propria (mp) were classified as the "shallow group", and 34 patients whose tumors invaded the ss were classified as the "deep group". The EUS findings were compared between the two groups.

Results: An irregular (narrow or thickened) LHEL was significantly more frequently observed on EUS in the deep group than in the shallow group. The diagnosis of ss invasion based on an irregular LHEL had the highest sensitivity and accuracy among the EUS imaging parameters (sensitivity 97.1% (33/34), specificity 86.7% (13/15), accuracy 93.8% (46/49)). When the deep group was limited to patients with a tumor depth of ss, the results were similar. When an irregular LHEL was used, the diagnostic accuracy of GBMTs with ss invasion was not significantly different between EUS specialists and beginners.

Conclusions: The observation of an irregular (thickened or narrow) LHEL observed on EUS could be a reliable and simple method of diagnosing GBMTs with ss invasion and could contribute to choosing an appropriate surgical method.
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http://dx.doi.org/10.1186/s12885-021-08017-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972348PMC
March 2021

Tracheobronchial Obstruction Due to Blood Clots in Acute Pulmonary Embolism with Cardiac Arrest Managed with Extracorporeal Membrane Oxygenation.

Intern Med 2021 Mar 15. Epub 2021 Mar 15.

Department of Cardiology, Fujieda Municipal General Hospital, Japan.

A 66-year-old Japanese woman developed pulseless electrical activity following an acute pulmonary embolism and was treated with thrombolytic therapy. She remained hemodynamically unstable and therefore underwent extracorporeal membrane oxygenation (ECMO). While receiving treatment with ECMO, blood clots induced by endobronchial hemorrhage caused tracheobronchial airway obstruction, leading to ventilatory defect. Furthermore, her cardiac function improved, resulting in cerebral hypoxemia progression. Therefore, the blood clots were removed with a Fogarty balloon catheter and endobronchial urokinase administration, resulting in improvement in her respiratory condition. Finally, ECMO was decannulated, and the patient was discharged from our hospital without difficulties in her activities of daily living.
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http://dx.doi.org/10.2169/internalmedicine.6856-20DOI Listing
March 2021

Effect of Empagliflozin as an Add-On Therapy on Decongestion and Renal Function in Patients With Diabetes Hospitalized for Acute Decompensated Heart Failure: A Prospective Randomized Controlled Study.

Circ Heart Fail 2021 03 5;14(3):e007048. Epub 2021 Mar 5.

Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan (S.T., S.S., A.S.).

Background: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure.

Methods: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula.

Results: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups.

Conclusions: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007048DOI Listing
March 2021

Two cases of gastric adenocarcinoma with enteroblastic differentiation resected by endoscopic submucosal dissection.

Clin J Gastroenterol 2021 Feb 24. Epub 2021 Feb 24.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is rare, highly malignant, and has higher vascular invasion and metastasis rates than conventional differentiated gastric cancer (CDGC). We report two cases of GAED that underwent curative resection by endoscopic submucosal dissection (ESD). Case 1 was an 82-year-old man with an elevated lesion in the gastric cardia. Biopsy revealed well-differentiated tubular adenocarcinoma. Pathological diagnosis of the ESD specimen revealed intramucosal gastric cancer without lymphovascular invasion (LVI). Although the surface layer of the lesion showed well and moderately differentiated tubular adenocarcinoma, clear cytoplasmic cancer cells positive for Sal-like protein-4 (SALL4) and Glypican-3 were found in a part of the deep layer. Therefore, GAED was diagnosed as present in a part of the whole lesion and covered with CDGC. Case 2 was an 83-year-old man with an elevated lesion in the gastric angulus. Biopsy revealed papillary and well-differentiated tubular adenocarcinomas. Pathological diagnosis of the ESD specimen revealed intramucosal gastric cancer without LVI. The entire lesion was occupied by papillary and tubular cancer cells, and had clear vesicles. Pure GAED was diagnosed, because the cells were SALL4 positive. In both cases, resection was curative despite the difference in pathological features.
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http://dx.doi.org/10.1007/s12328-021-01356-zDOI Listing
February 2021

Effects of anti-thrombotic drugs on all-cause mortality after upper gastrointestinal bleeding in Japan: A multicenter study with 2205 cases.

Dig Endosc 2021 Feb 21. Epub 2021 Feb 21.

Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.

Objects: Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB.

Methods: Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents.

Results: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti-thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non-users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%).

Conclusions: Although the usage of anti-thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti-thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti-thrombotic agents.
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http://dx.doi.org/10.1111/den.13961DOI Listing
February 2021

Efficacy of Sodium Carboxymethylcellulose Compared to Sodium Hyaluronate as Submucosal Injectant for Gastric Endoscopic Submucosal Dissection: A Randomized Controlled Trial.

Digestion 2021 Feb 19:1-7. Epub 2021 Feb 19.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Introduction: Sodium hyaluronate (SH) is a useful submucosal injectant for gastric endoscopic submucosal dissection (ESD). On the other hand, sodium carboxymethylcellulose (SCMC), which has high viscosity, has also been applied clinically. We evaluated the efficacy of SCMC compared to that of SH in gastric ESD.

Methods: A prospective randomized controlled trial was conducted to assess the efficacy of 1.0% SCMC as the injectant (SCMC group) compared to 0.4% SH (SH group) for ESD of gastric neoplasms. The primary end point was the procedure time of ESD. Secondary end points were treatment outcomes such as en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment (visual analog scale, 1-10 points), adverse events, and rate of ulcer healing 8 weeks after ESD.

Results: A total of 60 patients were enrolled between October 2014 and October 2018, and 30 patients were allocated in each group. The procedure time (mean ± SD, minutes) was not significantly different between the SCMC (74.7 ± 54.5) and SH groups (67.1 ± 41.4) (p = 0.547). Furthermore, there were no differences between the 2 groups in terms of en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment, and rate of ulcer healing. No serious adverse events were observed in either group.

Conclusion: SCMC was comparable to SH in terms of procedure time, treatment outcome, and ease and safety of treatment in gastric ESD. Further studies are needed to demonstrate the differences between the 2 injectants.
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http://dx.doi.org/10.1159/000513148DOI Listing
February 2021

Rate Versus Rhythm Control in Tachycardia-Induced Cardiomyopathy Patients with Persistent Atrial Flutter.

Int Heart J 2021 ;62(1):119-126

Department of Cardiology, Fujieda Municipal General Hospital.

Tachycardia-induced cardiomyopathy (TIC) is a potentially reversible cardiomyopathy caused by tachyarrhythmia. For atrial flutter (AFL) -induced TIC, a rhythm control strategy, such as catheter ablation, has been recommended. However, the efficacy of rate control has remained unclear due to the difficulty of achieving control using arrhythmic medications.We prospectively assessed 47 symptomatic heart failure (HF) patients with left ventricular ejection fraction (LVEF) < 50% and suspected persistent AFL-induced TIC. Patients were divided into the rhythm control strategy (n = 22; treatment with catheter ablation or electrical cardioversion) and rate control strategy (n = 25; treatment with bisoprolol) groups. The latter was further divided into the strict rate control strategy (average heart rate < 80 bpm) and lenient rate control strategy (average heart rate < 110 bpm) subgroups. The primary outcome was left ventricular (LV) function recovery, which was defined as an increase in LVEF ≥ 20% or to a value of ≥ 55% after 6 months.In the rhythm control strategy group, more patients achieved LV function recovery after 6 months (95.2% versus 60.9%, P = 0.010). The cumulative incidence of worsening HF events was significantly higher in the rate control strategy group than in the rhythm control strategy group (hazard ratio, 4.66; 95% confidence interval, 1.01-21.57). The subgroup study revealed the advantage of the strict rate control strategy for achieving LV function recovery (83.3% versus 36.4%, P = 0.036).The rate control strategy was significantly inferior to the rhythm control strategy for the LV function recovery in TIC patients with persistent AFL. Our findings suggest that the strict rate control strategy should be aimed if the rhythm control strategy cannot be performed.
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http://dx.doi.org/10.1536/ihj.20-266DOI Listing
February 2021

Hilar Malignant Biliary Obstruction Treated with Four Metallic Stents Involving a New Slim Device.

Intern Med 2021 Feb 1. Epub 2021 Feb 1.

Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan.

Endoscopic hilar multiple stenting is challenging. A 68-year-old patient had self-expandable metallic stents (SEMSs) inserted for unresectable hilar malignant biliary obstruction. After the SEMSs were inserted into the left hepatic duct and bile duct branch of segment (B) 6, a new SEMS with a wide mesh and slim delivery system was inserted into the right anterior hepatic duct. However, liver abscess and dilated B7 were observed on computed tomography; therefore, an additional new SEMS was quickly and easily inserted into B7. After the placement of these four SEMSs, the liver abscess improved. The new SEMS was effective for hilar multiple biliary drainage.
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http://dx.doi.org/10.2169/internalmedicine.6356-20DOI Listing
February 2021

Prognostic value of impaired hepato-renal function and liver fibrosis in patients admitted for acute heart failure.

ESC Heart Fail 2021 Apr 20;8(2):1274-1283. Epub 2021 Jan 20.

Division of Cardiology, Osaka General Medical Center, 3-1-56, Mandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.

Aims: Cardiohepatic interactions have been a focus of attention in heart failure (HF). The model for end-stage liver disease excluding international normalized ratio (MELD-XI) score has been shown to be useful for predicting poor outcomes in patients with acute decompensated HF (ADHF). Furthermore, the fibrosis-4 (FIB-4) index, a simple marker to assess liver fibrosis, predicts adverse prognoses in patients with HF as well. However, there is little information available on the prognostic significance of the combination of the MELD-XI score and FIB-4 index in patients with ADHF and its association with left ventricular ejection fraction (LVEF) subgroup.

Methods And Results: We prospectively studied 466 consecutive patients who were admitted for ADHF [HF with reduced LVEF (LVEF < 40%): n = 164, HF with mid-range LVEF (40% ≤ LVEF < 50%): n = 104, and HF with preserved LVEF (LVEF ≥ 50%): n = 198]. We calculated the MELD-XI score and FIB-4 indices at discharge. The primary endpoint was all-cause death (ACD). During the mean follow-up period of 2.8 years, 143 patients had ACD. In the multivariate Cox analysis, the MELD-XI score and FIB-4 index were independently associated with ACD. Patients were stratified into the following three groups according to the median value of MELD-XI score (=11) and FIB-4 index (=2.13): Group 1 had both a low MELD-XI score and a low FIB-4 index; Group 2 had either a high MELD-XI score (MELD-XI score ≥11) or a high FIB-4 index (FIB-4 index ≥2.13); and Group 3 had both a high MELD-XI score and a high FIB-4 index. Kaplan-Meier analysis revealed that Group 2 and Group 3 had a significantly greater risk of ACD than Group 1 [Group 2 vs. Group 1: adjusted hazard ratio, 2.48 (95% confidence interval: 1.75-3.53), P < 0.0001; Group 3 vs. Group 1: adjusted hazard ratio, 7.03 (95% confidence interval: 3.95-13.7), P < 0.0001]. In addition, the patients with both a higher MELD-XI score and FIB-4 index showed a significantly higher risk of ACD also in the patients with HF with reduced LVEF, HF with mid-range LVEF, and HF with preserved LVEF (all P < 0.0001).

Conclusions: The combination of MELD-XI score and FIB-4 index may be useful for stratifying patients at risk for ACD in patients with ADHF, irrespective of LVEF.
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http://dx.doi.org/10.1002/ehf2.13195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006618PMC
April 2021

Incremental prognostic value of cardiac metaiodobenzylguanidine imaging over the co-morbid burden in acute decompensated heart failure.

ESC Heart Fail 2021 Apr 12;8(2):1167-1177. Epub 2021 Jan 12.

Division of Cardiology, Osaka General Medical Center, Osaka, Japan.

Aims: Co-morbidities are associated with poor clinical outcomes in patients with chronic heart failure, while cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging provides prognostic information in such patients. We sought to prospectively investigate the incremental prognostic value of cardiac MIBG imaging over the co-morbid burden, in patients admitted for acute decompensated heart failure (ADHF).

Methods And Results: In 433 consecutive ADHF patients with survival to discharge, we measured the co-morbidity using age-adjusted Charlson co-morbidity index (ACCI), commonly employed to evaluate a weighted and scored co-morbid condition, adding additional points for age. In cardiac MIBG imaging, the cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image. Over a follow-up period of 2.9 ± 1.5 years, 160 patients had a cardiac event (a composite of cardiac death and unplanned hospitalization for worsening heart failure). Patients with high ACCI (≥6: median value) had a significantly greater risk of a cardiac event. In multivariate Cox analysis, the ACCI and late HMR were significantly and independently associated with a cardiac event. In both high and low ACCI subgroups (ACCI ≥ 6 and <6, respectively), patients with low late HMR had a significantly greater risk of a cardiac event (high ACCI: 51% vs. 34% P = 0.0026, adjusted HR 1.74 [1.21-2.51]; low ACCI: 34% vs. 17%, P = 0.0228, adjusted HR 2.19 [1.10-4.37]).

Conclusions: Cardiac MIBG imaging could provide additional prognostic information over ACCI, which was also promoted to be a useful risk model, in patients admitted for ADHF.
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http://dx.doi.org/10.1002/ehf2.13173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006734PMC
April 2021

A case of eosinophilic esophagitis with autoimmune polyendocrine syndrome type 2, including autoimmune gastritis.

Clin J Gastroenterol 2021 Apr 7;14(2):460-465. Epub 2021 Jan 7.

Division of Gastroenterology, Department of Internal Medicine 2, Kawasaki Medical School, Okayama, Japan.

Both eosinophilic esophagitis (EoE) and autoimmune polyendocrine syndrome (APS) are relatively rare diseases in Japan. We herein report a case of EoE with APS in a 67-year-old Japanese man who presented with chest pain and dysphagia. On the basis of endoscopic findings and histological analysis, we diagnosed the patient with EoE along with autoimmune gastritis. Additional serological examinations revealed the presence of Hashimoto's thyroiditis and type 1 diabetes, which led to the final diagnosis of APS. His symptoms did not respond to treatment with a proton-pump inhibitor but improved with topical steroid therapy. This case of coexisting EoE and APS-2 is quite rare and has several implications for the pathogenesis of both conditions.
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http://dx.doi.org/10.1007/s12328-020-01333-yDOI Listing
April 2021

Gastric carcinoma with lymphoid stroma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Clin J Gastroenterol 2021 Apr 1;14(2):471-477. Epub 2021 Jan 1.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

A 78-year-old man with a subepithelial lesion (SEL) in the gastric body and two carcinomas in the gastric antrum was referred to our hospital. Following a diagnosis of SEL, the patient was followed-up by esophagogastroduodenoscopy annually for 4 years. Although the SEL had increased in size over the years, histological evaluation of the forceps biopsies did not reveal any significant findings. We detected a hypoechoic mass in the submucosa by endoscopic ultrasonography, and suspected the lesion to be an aberrant pancreas or mesenchymal tumor. The patient first underwent endoscopic submucosal dissection for the 2 gastric cancers. Histological examination of the resected specimens revealed intramucosal well-differentiated tubular adenocarcinomas. Next, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed for the gastric SEL. Aspirated specimens revealed an adenocarcinoma with lymphocyte infiltration. The lesion was diagnosed as a gastric carcinoma with lymphoid stroma (GCLS). Subsequently, he underwent distal gastrectomy, and the surgical specimen was confirmed as GCLS corresponding to preoperative diagnosis. In addition, the adenocarcinoma cells were positive for Epstein-Barr (EB) virus-encoded small RNA-1 by in situ hybridization. Finally, the lesion was diagnosed as GCLS associated with EB virus. Thus, EUS-FNA is advantageous for diagnosing GCLS associated with EB virus.
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http://dx.doi.org/10.1007/s12328-020-01300-7DOI Listing
April 2021

Prevention of Stricture after Endoscopic Submucosal Dissection for Superficial Esophageal Cancer: A Review of the Literature.

J Clin Med 2020 Dec 23;10(1). Epub 2020 Dec 23.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima-City 960-1295, Fukushima, Japan.

Endoscopic resection has been the standard treatment for intramucosal esophageal cancers (ECs) because of the low risk of lymph node metastases in the lesions. In recent years, endoscopic submucosal dissection (ESD), which can resect large ECs, has been performed. However, the risk of esophageal stricture after ESD is high when the mucosal defect caused by the treatment exceeds 3/4 of the circumference of the lumen. Despite the subsequent high risk of luminal stricture, ESD has been performed even in cases of circumferential EC. In such cases, it is necessary to take measures to prevent stricture. Therefore, in this review, we aimed to clarify the current status of stricture prevention methods after esophageal ESD based on previous literature. Although various prophylactic methods have been reported to have stricture-preventing effects, steroid injection therapy and oral steroid administration are mainstream. However, in cases of circumferential EC, both steroid injection therapy and oral steroid administration cannot effectively prevent luminal stricture. To solve this issue, clinical applications, such as tissue shielding methods with polyglycolic acid sheet, autologous oral mucosal epithelial sheet transplantation, and stent placement, have been developed. However, effective prophylaxis of post-ESD mucosal defects of the esophagus is still unclear. Therefore, further studies in this research field are needed.
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http://dx.doi.org/10.3390/jcm10010020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796365PMC
December 2020

Urinary mulberry bodies as a potential biomarker for early diagnosis and efficacy assessment of enzyme replacement therapy in Fabry nephropathy.

Nephrol Dial Transplant 2020 Dec 24. Epub 2020 Dec 24.

Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.

Background: The inability of enzyme replacement therapy (ERT) to prevent progression of Fabry nephropathy (FN) in the presence of >1 g/day proteinuria underscores the necessity of identifying effective biomarkers for early diagnosis of FN preceding proteinuria. Here we attempted to identify biomarkers for early detection of FN.

Methods: Fifty-one Fabry disease (FD) patients were enrolled. Urinary mulberry bodies (uMBs) were immunostained for globotriaosylceramide (Gb3) and renal cell markers to determine their origin. The association between semiquantitative uMB excretion and the histological severity of podocyte vacuolation was investigated in seven patients using the vacuolated podocyte:glomerular average area ratio. The association between the semiquantitative estimate of uMB excretion and duration of ERT was analyzed. A longitudinal study was conducted to assess the effect of ERT on uMB excretion.

Results: Thirty-two patients (63%) had uMBs, while only 31% showed proteinuria. The uMBs were positive for Gb3, lysosomal-associated membrane protein 1 and podocalyxin, suggesting they were derived from lysosomes with Gb3 accumulation in podocytes. We observed more severe podocyte vacuolation with increased uMB excretion (P = 0.03 for trend); however, the same was not observed with increased proteinuria. The percentage of patients with substantial uMB excretion increased with shorter ERT duration (P = 0.018). Eighteen-month-long ERT reduced uMB excretion (P = 0.03) without affecting proteinuria.

Conclusions: uMB excretion, implying ongoing podocyte injury, preceded proteinuria in most patients. Semiquantitative uMB estimates can serve as novel biomarkers for early FN diagnosis and for monitoring the efficacy of FD-specific therapies.
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http://dx.doi.org/10.1093/ndt/gfaa298DOI Listing
December 2020

An unexpected butadiene diolepoxide-mediated genotoxicity implies alternative mechanism for 1,3-butadiene carcinogenicity.

Chemosphere 2021 Mar 30;266:129149. Epub 2020 Nov 30.

Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

1,3-Butadiene (BD) is abundant in combustion products such as cigarette smoke. While BD has been classified as a known human carcinogen, a long-standing question is the identity of the ultimate carcinogenic metabolite in humans. We hypothesize that 3,4-epoxybutane-1,2-diol (EBD) may play a critical role in human carcinogenesis due to its high bioavailability. We utilized a differential toxicity assay for BD metabolites and newly synthesized EBD analogs in a series of isogenic chicken cells lacking specific DNA repair proteins to address the mode of action of BD genotoxicity and infer a mode of action. Surprisingly, as with the diepoxide 1,2:3,4-diepoxybutane (DEB), the monoepoxide EBD showed remarkable toxicity to cells deficient in Fanconi anemia (FANC) genes. This observation suggests that EBD may be transformed into a bifunctional metabolite and forms interstrand cross-links. EBD and its analog with a hydroxy substituent at C1 were found to be highly toxic to FANCD2-deficient chicken and human cells. The Results suggest that EBD may be transformed to a bifunctional epoxy aldehyde, perhaps by alcohol dehydrogenase, to which the observed FANC sensitivity could be attributed. The implications of this study are very important in considering mechanisms by which EBD may cause leukemia and lymphoma in humans exposed to BD.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129149DOI Listing
March 2021

Differences in emergency endoscopy outcomes according to gastrointestinal bleeding location.

Scand J Gastroenterol 2021 Jan 17;56(1):86-93. Epub 2020 Nov 17.

Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan.

Background And Aim: With recent technological advances in the field of endoscopic hemostasis, the prognosis of patients with gastrointestinal (GI) bleeding has improved. However, few studies have reported on the clinical course of patients with GI bleeding. This study aimed to evaluate the differences in clinical outcomes of patients with lower GI bleeding (LGIB) compared with upper GI bleeding (UGIB) and the factors related to their prognosis.

Methods: Patients who had undergone emergency endoscopy for GI bleeding were retrospectively reviewed. The severity of GI bleeding was evaluated using the Glasgow-Blatchford (GB), AIMS65, and NOBLADS scores. Patients in whom obvious GI bleeding relapsed and/or iron deficiency anemia persisted after emergency endoscopy were considered to exhibit rebleeding.

Results: We reviewed 1697 consecutive patients and divided them into UGIB (1054 patients) and LGIB (643 patients) groups. The proportion of patients with rebleeding was significantly greater in the UGIB group than in the LGIB group; the mortality rate was significantly higher in the UGIB group than in the LGIB group. Multivariate analysis showed that a GB score ≥12 and an AIMS65 score ≥2 were significantly associated with rebleeding in the UGIB group, whereas a NOBLADS score ≥4 was significantly associated with rebleeding in the LGIB group. Notably, the influence of emergency endoscopy differed according to GI bleeding location.

Conclusions: The clinical course was significantly worse in patients with UGIB than in patients with LGIB. The influence of emergency endoscopy differed according to GI bleeding location.
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http://dx.doi.org/10.1080/00365521.2020.1847316DOI Listing
January 2021

Efficacy of EUS-guided FNB using a Franseen needle for tissue acquisition and microsatellite instability evaluation in unresectable pancreatic lesions.

BMC Cancer 2020 Nov 11;20(1):1094. Epub 2020 Nov 11.

Department of Gastroenterology, Fukushima Medical University, School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

Background: The efficacy of immune checkpoint blockade in the treatment of microsatellite instability (MSI)-high tumors was recently reported. Therefore, the acquisition of histological specimens is desired in cases of unresectable solid pancreatic lesions (UR SPLs). This study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for UR SPL tissue acquisition and MSI evaluation.

Methods: A total of 195 SPL patients who underwent EUS-guided fine-needle aspiration (EUS-FNA) or EUS-FNB (EUS-FNAB) between January 2017 and March 2020 were enrolled in this study. Among them, 89 SPL patients (FNB: 28, FNA: 61) underwent EUS-FNAB using a 22-G needle (UR SPLs: 58, FNB: 22, FNA: 36) (UR SPLs after starting MSI evaluation: 23, FNB: 9, FNA: 14).

Results: The puncture number was significantly lower with FNB than with FNA (median (range): 3 (2-5) vs 4 (1-8), P <  0.01, UR SPLs: 3 (2-5) vs 4 (1-8), P = 0.036). Histological specimen acquisition was more commonly achieved with FNB than with FNA (92.9% (26/28) vs 68.9% (42/61), P = 0.015, UR SPLs: 100% (22/22) vs 72.2% (26/36), P <  0.01). The histological specimen required for MSI evaluation was acquired more often with FNB than with FNA (88.9% (8/9) vs 35.7% (5/14), P = 0.03).

Conclusions: EUS-FNB using a Franseen needle is efficient for histological specimen acquisition and sampling the required amount of specimen for MSI evaluation in UR SPL patients.
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http://dx.doi.org/10.1186/s12885-020-07588-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659127PMC
November 2020

Gastric Hyperplastic Polyps after Argon Plasma Coagulation for Gastric Antral Vascular Ectasia in Patients with Liver Cirrhosis: A Case Suggesting the "Gastrin Link Theory".

Intern Med 2021 Apr 28;60(7):1019-1025. Epub 2020 Oct 28.

Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Japan.

We herein report a case of gastric hyperplastic polyps after argon plasma coagulation (APC) for gastric antral vascular ectasia (GAVE) in the antrum of a 65-year-old man with liver cirrhosis and hypergastrinemia induced by long-term proton pump inhibitor (PPI) use. Two years after APC therapy, endoscopy demonstrated multiple gastric polyps in the antrum and angle. A gastric polyp biopsy indicated foveolar epithelium hyperplasia, which was diagnosed as gastric hyperplastic polyps. One year after switching to an H2 blocker antagonist, endoscopy revealed that the polyps and GAVE had disappeared, with normal gastrin levels suggesting that PPI-induced hypergastrinemia had caused gastric hyperplastic polyps after APC therapy, and the polyps had disappeared after discontinuing PPIs.
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http://dx.doi.org/10.2169/internalmedicine.5837-20DOI Listing
April 2021

A Blood-based Gene-expression Scoring System for Cancer Screening in Patients With Branch-duct Intraductal Papillary Mucinous Neoplasms.

Anticancer Res 2020 Nov;40(11):6551-6561

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Background: In patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), we aimed to develop a novel blood-based biomarker utilizing a gene-expression profile for the detection of pancreatic malignancies, such as IPMN-derived carcinoma (IPMC) or pancreatic ductal adenocarcinoma (PDAC).

Patients And Methods: We enrolled 40 patients with pancreatic tumors (24 BD-IPMNs, four IPMCs and 12 PDACs) and identified the characteristic gene-expression profiles in pancreatic malignancies. Subsequently, we constructed a gene-expression scoring system for the proper diagnosis of pancreatic malignancies. The result was validated in 14 patients (five IPMNs, three IPMCs and six PDACs).

Results: The scoring system utilizing the expression levels of 13 genes showed high diagnostic yield (sensitivity=94.0%, specificity=92.0% and area under the curve=0.94), which was confirmed in the validation set. Furthermore, its diagnostic yield was not reduced even in early-stage pancreatic malignancies (sensitivity=85.0%, specificity=93.0% and area under the curve=0.88).

Conclusion: We developed a blood-based gene expression scoring system for cancer screening in patients with BD-IPMNs.
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http://dx.doi.org/10.21873/anticanres.14680DOI Listing
November 2020

The "caterpillar sign": a novel endoscopic indicator of eosinophilic esophagitis.

Esophagus 2021 Jan 23;18(1):156-162. Epub 2020 Oct 23.

Division of Gastroenterology, Department of Internal Medicine 2, Kawasaki Medical School, Okayama, Japan.

Background: Although several endoscopic findings of eosinophilic esophagitis (EoE), such as the EoE endoscopic reference score (EREFS), have been reported thus far, these endoscopic findings exhibit low specificity. Furthermore, most of these endoscopic findings were evaluated solely in patients from Western nations. We have recently noted a fragile, protruded mucosal lesion sandwiched between longitudinal furrows (similar to caterpillar tracks) on the esophagus in patients with EoE. We have termed this novel finding the "caterpillar sign". This study evaluated the clinical significance of the caterpillar sign and the EREFS for diagnosis of EoE in Japanese patients.

Methods: We retrospectively analyzed endoscopic images from 165 consecutive patients who underwent tissue collection on suspicion of EoE. We compared the clinical significance between the EREFS and the caterpillar sign. We defined EoE as the presence of ≥ 15 eosinophils on esophageal mucosa per high-power field; control images had < 15 eosinophils per high-power field. For evaluation of endoscopic diagnosis capacity using the total EREFS, 2 points was set as the cutoff value. The presence or absence of the caterpillar sign was evaluated.

Results: The sensitivity, specificity, positive predictive value, and negative predictive value of total EREFS ≥ 2 for the diagnosis of EoE were 100%, 56.2%, 56.6%, and 100%; for the caterpillar sign, those values were 83.3%, 98.1%, 96.2%, and 91.2%, respectively. Interobserver agreement for identification of the caterpillar sign was substantial (κ = 0.80) CONCLUSIONS: The caterpillar sign could be a novel reliable indicator for endoscopic diagnosis of EoE.
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http://dx.doi.org/10.1007/s10388-020-00791-0DOI Listing
January 2021

The Dramatic Haemostatic Effect of Covered Self-expandable Metallic Stents for Duodenal and Biliary Bleeding.

Intern Med 2021 Mar 21;60(6):883-889. Epub 2020 Oct 21.

Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan.

Bilio-duodenal bleeding, such as post-endoscopic sphincterotomy (EST) bleeding, common bile duct (CBD) bleeding after endoscopic retrograde cholangiopancreatography (ERCP), and duodenal bleeding due to malignant tumour invasion, can sometimes become severe. Six cases of refractory bilio-duodenal bleeding were stanched via covered self-expandable metallic stent (CSEMS) insertion, even though three of the patients had a history of gastrectomy. The dumbbell-shaped CSEMS was useful for managing post-EST bleeding. Additional duodenal CSEMS insertion was useful for the patient who had previously undergone uncovered SEMS insertion, and no migration of the CSEMS was observed. CSEMS insertion was useful for treating refractory bilio-duodenal haemorrhaging.
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http://dx.doi.org/10.2169/internalmedicine.6018-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024959PMC
March 2021

LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury.

Nat Cell Biol 2020 10 28;22(10):1252-1263. Epub 2020 Sep 28.

Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.

Sensing and clearance of dysfunctional lysosomes is critical for cellular homeostasis. Here we show that transcription factor EB (TFEB)-a master transcriptional regulator of lysosomal biogenesis and autophagy-is activated during the lysosomal damage response, and its activation is dependent on the function of the ATG conjugation system, which mediates LC3 lipidation. In addition, lysosomal damage triggers LC3 recruitment on lysosomes, where lipidated LC3 interacts with the lysosomal calcium channel TRPML1, facilitating calcium efflux essential for TFEB activation. Furthermore, we demonstrate the presence and importance of this TFEB activation mechanism in kidneys in a mouse model of oxalate nephropathy accompanying lysosomal damage. A proximal tubule-specific TFEB-knockout mouse exhibited progression of kidney injury induced by oxalate crystals. Together, our results reveal unexpected mechanisms of TFEB activation by LC3 lipidation and their physiological relevance during the lysosomal damage response.
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http://dx.doi.org/10.1038/s41556-020-00583-9DOI Listing
October 2020