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Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

The prevalence of gastric cancer after eradication (GCAE) is increasing dramatically in Japan. GCAE has characteristic features, and we must understand these features in endoscopic examinations. Differentiated cancer types were frequently found after eradication and included characteristic endoscopic features such as reddish depression (RD). However, benign RD can be difficult to distinguish from gastric cancer because of histological alterations in the surface structures (nonneoplastic epithelium or epithelium with low-grade atypia [ELA]) as well as multiple appearances of RD. Recently, we clarified similar alterations in genetic mutations between ELA and gastric cancer, suggesting that ELA is derived from gastric cancer. Clinically, submucosal invasive cancer was frequently found in patients after eradication therapy even if they received annual endoscopic surveillance. We can improve the diagnostic ability using image-enhanced endoscopy with magnified observation. (Gut Liver 2021;15:338-345)

We herein report a case of aortitis induced by granulocyte colony-stimulating factor (G-CSF) that coincided with lung injury, splenomegaly, and cutaneous manifestations during treatment for recurrent extraosseous mucinous chondrosarcoma. Computed tomography revealed large-vessel vasculitis, splenomegaly, and pulmonary interstitial changes. Treatment with prednisolone was successful. Because sarcoma is a rare disease, this case is valuable for showing clinicians that G-CSF preparations could cause aortitis regardless of the patient's underlying diseases or therapeutic pharmacological backgrounds.

Attenuation correction (AC) is crucial for ensuring the quantitative accuracy of positron emission tomography (PET) imaging. However, obtaining accurate μ-maps from brain-dedicated PET scanners without AC acquisition mechanism is challenging. Therefore, to overcome these problems, we developed a deep learning-based PET AC (deep AC) framework to synthesize transmission computed tomography (TCT) images from non-AC (NAC) PET images using a convolutional neural network (CNN) with a huge dataset of various radiotracers for brain PET imaging. The proposed framework is comprised of three steps: (1) NAC PET image generation, (2) synthetic TCT generation using CNN, and (3) PET image reconstruction. We trained the CNN by combining the mixed image dataset of six radiotracers to avoid overfitting, including [18F]FDG, [18F]BCPP-EF, [11C]Racropride, [11C]PIB, [11C]DPA-713, and [11C]PBB3. We used 1261 brain NAC PET and TCT images (1091 for training and 70 for testing). We did not include [11C]Methionine subjects in the training dataset, but included them in the testing dataset. The image quality of the synthetic TCT images obtained using the CNN trained on the mixed dataset of six radiotracers was superior to those obtained using the CNN trained on the split dataset generated from each radiotracer. In the [18F]FDG study, the mean relative PET biases of the emission-segmented AC (ESAC) and deep AC were 8.46 ± 5.24 and − 5.69 ± 4.97, respectively. The deep AC PET and TCT AC PET images exhibited excellent correlation for all seven radiotracers (R2 = 0.912–0.982). These results indicate that our proposed deep AC framework can be leveraged to provide quantitatively superior PET images when using the CNN trained on the mixed dataset of PET tracers than when using the CNN trained on the split dataset which means specific for each tracer.

The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.

Aim To investigate the clinical factors and factors that affect the decisions regarding storage of cryopreserved embryos obtained using assisted reproductive technology. Methods Clinical characteristics affecting the decisions regarding cryopreserved embryos were analyzed in 5724 Japanese couples who underwent in vitro fertilization (IVF) or intra-cytoplasmic sperm insemination (ICSI) and embryo transfer over 4 years since April 2015 at our clinic. Statistical analysis was carried out using JMP software. Results The number of oocytes retrievals and embryos stored, outcomes and number of children, and age of the female patients and male partners were related to the decision-making regarding cryopreserved embryos. Childbearing and no wish for another child were the major reasons for discontinuing embryo storage. The number of oocytes retrievals and embryos in storage, age of the female patients, and sex of the child were independently associated with this decision-making in 2682 patients with a single child. Women with male children were more likely to choose discontinuation of embryo storage than those with female children. Conclusion Already having a child and not wishing for further treatment due to age along with the presence of a male child affect the decision to continue or discontinue embryo storage in Japanese patients with infertility.

Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF).We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients' ICU stays.Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines-Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P0.001) were independently associated with the development of delirium.Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status.

We herein report on two male patients (age, 22 and 44 years) who were referred to our department with swelling of the upper right arm after attending other hospitals. Right subclavian vein thrombosis was demonstrated by ultrasonography and they were then further evaluated by contrast-enhanced computed tomography (CT). Successful treatment involved venous thrombectomy in one patient and anticoagulant therapy in the other. Paget-Schhroetter syndrome was confirmed using standard vascular ultrasonography. Despite the accuracy of this method for diagnosing Paget-Schroetter syndrome, some cases are difficult to confirm. We reviewed 29 previously published case reports of Paget-Schroetter syndrome and analyzed the patient baseline characteristics, time to diagnosis, and the diagnostic methods used.

BACKGROUND AND AIM: In Japan, the prevalence of autoimmune gastritis (AIG) is assumed to be very low. With the recent rapid decrease in Helicobacter pylori (Hp) prevalence, reports on AIG are increasing. This multicenter registry study aimed to clarify the characteristics of AIG, especially its endoscopic appearance. METHODS: A total of 245 patients with AIG from 11 institutions in Japan from January 2010 to October 2016 were included, and their clinical and endoscopic findings were evaluated. RESULTS: Mean age was 67.2±11.4years, and 63.7% of the participants were women. The most common approach to diagnose AIG was endoscopic examination. Repeated incorrect treatment for Hp infection, due to a false-positive result in 13 C-urea breath test, ranked third among the basis for diagnosis of AIG. Associated gastric lesions were type 1 neuroendocrine tumor (11.4%), adenocarcinoma (9.8%), and hyperplastic polyps (21.1%). Corpus pan-atrophy was the most common appearance (90.1%); however, remnant oxyntic mucosa was found in 31.5% of the patients (flat, localized type, 48.6%). Sticky adherent dense mucus and scattered minute whitish protrusions were also observed in approximately 30% of the patients. Despite the prevailing presumption of the antral mucosa remaining normal, 42.3% of the patients presented with various extents of atrophy, and patchy redness and circular wrinkle-like patterns were both observed in approximately 20% of the patients. CONCLUSIONS: The present study showed some prominent clinical characteristics and endoscopic findings of AIG. We believe that our study will facilitate the diagnosis of potential AIG., 著者最終稿（査読済み）, © 2019 Japan Gastroenterological Endoscopy Society.

Objective The Chicago classification using high-resolution manometry (HRM) has been proposed for the diagnosis of esophageal motility disorders. However, HRM is expensive, and few patients are likely to benefit from this method. We established a method using a raised infusion catheter called "esophageal manometry using a trans-nasal endoscope". In this study, we examined the clinical utility of this new method for the assessment of patients with dysphagia. Methods We enrolled 124 consecutive patients who complained of dysphagia and were suspected of having esophageal motility disorders. Patients underwent manometry using a trans-nasal endoscope at Hiroshima University Hospital from September 2008 to December 2018. An esophageal biopsy was performed during the procedure from the thoracic esophagus to detect eosinophilic esophagitis. In addition, we examined the clinical courses of patients diagnosed with achalasia. Results The diagnostic ability of manometry using a trans-nasal endoscope was 98%, and no major complications associated with the procedure were recorded. About 30% of patients were diagnosed with achalasia, and most (77%) were well controlled by medications or balloon dilation. One patient was diagnosed with eosinophilic esophagitis. Conclusion Manometry using a trans-nasal endoscope is beneficial and can be used for the clinical management of patients with dysphagia.

Amid the global outbreak of coronavirus disease 2019 (COVID-19), it may be expected that low-toxicity natural compounds, such as Kampo formulas, will have a preventive effect on COVID-19. Although the biological properties and safety of the representative Kampo compounds, hochuekkito (HET) and kakkonto (KKT), have been confirmed in various animal model experiments, clinical studies, and a few human studies to induce biological effects on various infectious diseases without significant toxicity, it is unclear whether HET and KKT are safe and effective for COVID-19 prevention. The study population included healthcare workers (HCWs), as they are at a higher risk of infection than the other populations. We retrospectively investigated the immunological and preventive effects of HET and KTT against COVID-19. We included 27 HCWs (aged 21–72 years, F:M = 18:9) from hospitals and clinics of the Hokuriku-Tokai region. The HCWs received HET and KKT for general fatigue and myalgia during this period for 28 days. We obtained patient clinical data from electronic medical records. We analyzed the changes in immunomodulation before and after the administration of the formulas from residual specimens based on the expression of relevant surface markers. The specimens were also tested for the presence of antibodies against severe acute respiratory syndrome coronavirus 2. The following side effects were reported: abdominal discomfort in five patients, diarrhea in two, and loose or soft stool in three. All 27 HCWs tested negative for COVID-19 antibodies. HET and KKT administration significantly increased the absolute number of circulating lymphocytes expressing the activating receptors NKp46, NKp30, and suppressing receptor NKG2A. There was also a significant increase in the absolute number of circulating lymphocytes expressing the receptors TLR4, OX40, 4–1BB, GITR, PD-1, and ICOS. These data indicate that HET and KKT can enhance and modulate NK activity in circulating human immune cells. The immunomodulatory effects, such as activation and regulation of T cells, are consistent with a putative improvement in infectious immunosurveillance. An increase in the number of T cells and CD4/CD8-positive cells indicates an enhanced ability to protect against infection. HET and KKT may prevent the onset or worsening of COVID-19 through their immunomodulatory effects.

Background Exercise‐induced bronchoconstriction (EIB), a strong positive predictor of asthma, becomes progressively less frequent with age. Although asthma tends to become less common only in boys during adolescence, sex differences in EIB, especially in preschoolers, remain unclear. To find EIB for early diagnosis and intervention asthma, mass‐screening tests considering sex differences in preschoolers are needed. In this study, we investigated whether sex differences influence the prevalence and severity of EIB in prepubertal children aged 5–6 years. Methods Fifty‐one children aged 5–6 years who were attending a kindergarten in Matsuyama City, Ehime, Japan, were enrolled in this cross‐sectional study. The children underwent a 6‐minute free‐running test in 2015. The peak expiratory flow rate (PEFR) was measured before exercise and 0, 3, 10, and 20 minutes after exercise. The severity of EIB was classified according to the reduction in PEFR, measured as the difference between the postexercise PEFR and the highest pre‐exercise PEFR. Results Of the 51 children (23 boys and 28 girls) enrolled, the prevalence of EIB defined as three criteria: a ≥15%, ≥20%, or ≥25% decrease was 54.9% (28/51), 41.2% (21/51), and 25.5% (13/51), respectively. The prevalence of EIB defined as ≥25% decrease was significantly higher in girls than in boys (39.3% vs 8.7%, P = .013). In girls, the mean percentage change in PEFR was significantly higher 20 minutes than 10 minutes postexercise (P = .043). Conclusions Sex difference in the prevalence and severity of EIB should be considered when evaluating EIB, even in young, prepubertal children., Asthma tends to become less common in boys but more common in girls during the transition from childhood to adolescence, which appears to be influenced by sex hormones; however, sex differences in EIB, especially in preschool children, remain unclear. In this study, we investigated whether sex differences influence the prevalence and severity of EIB in prepubertal children aged 5–6 years.Sex difference in the prevalence and severity of EIB should be considered when evaluating EIB, even in young, prepubertal children.

Background Gastric cancer may develop after successful eradication of Helicobacter pylori, although the incidence is lower than in non-eradicated individuals. We previously reported the appearance of characteristic epithelium with low-grade atypia (ELA) on the surface of gastric cancer after H. pylori eradication. However, whether ELA originates from cancer after re-differentiation or from the non-cancerous surrounding mucosa is unknown. Methods We isolated ELA regions from 10 early gastric cancer patients and analyzed the nucleotide sequences for 90 oncogenes and 35 fusion oncogenes, comparing them with counterpart cancer tissue, normal gastric mucosa, and blood cell-derived DNA. Somatic mutations in each tissue were identified by comparing them with the sequences from whole blood-derived DNA. Result Gene alterations were observed in nine of the ten patients, and up to 42 and 70 somatic mutations were seen in cancer and ELA samples, respectively. Common mutations shared between cancer and ELA tissues were found in eight of these nine patients. In contrast, common mutations between non-cancer mucosa and ELA were only detected in one patient, who also had common mutation between cancer and ELA. ELA-specific nucleotide substitutions were seen in seven patients. In contrast, cancer-specific substitutions were only found in two patients. 18 out of 19 amino acid substitutions present in cancer tissue were also identified in ELA. These results suggest that ELA originated from cancer tissue and accumulated further nucleotide substitutions. Conclusions Differential diagnosis of ELA and normal mucosa should be carefully performed to prevent misdiagnosis of ELA as normal mucosa with atypia., This study was supported by grants from the Japan Society for the Promotion of Science (JSPS KAKENHI GrantNumber: 16K19379; https://www.jsps.go.jp/j-grantsinaid/).

BACKGROUND AND AIM The typical histology of Helicobacter pylori-uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H. pylori-uninfected patient and its prevalence in diffuse-type gastric cancer (DGC) within Japan. METHODS We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H. pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA. RESULTS Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H. pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P

A previously healthy 43-year-old man presented with durable occipitalgia for 1 month. Neurological examination revealed severe pain in the right C2 area accompanied by neck stiffness. Magnetic resonance imaging revealed an enhancing, polycystic intradural mass at the C2 level, occupying the left dorsolateral part of the spinal canal. In addition, a rim-like enhancement was found along the surfaces of the spinal cord. Blood tests did not show signs of infection. A lumbar spinal tap revealed albuminocytologic dissociation without cultured organisms. Cranial computed tomography scans taken 20 days later revealed an overt ventriculomegaly. The patient underwent a total tumor resection through hemilaminectomy of the C2. Intraoperatively, the left dorsal C2 roots were found to be extremely redundant due to the tumor and surrounding thickened arachnoids. The roots restored normal morphologies after resection of the arachnoids and tumor. Postoperatively, the patient's symptoms resolved and histological diagnosis was endodermal cyst. Four weeks later, a ventriculoperitoneal shunt was placed to treat progressive ventriculomegaly. A polycystic intradural mass of the upper cervical spine should assume an endodermal cyst that may cause contralateral occipitalgia and aseptic meningitis. Keywords: Endodermal cyst, Contralateral occipitalgia, Aseptic meningitis

Background Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined. Methods The results of gastric endoscopies, H. pylori infection tests, and PG values were retrospectively reviewed. Subjects were assigned to groups, including never-infected (with neither infection nor gastric mucosal atrophy), infected (with atrophy or findings indicating infection in endoscopy and positive infection tests except for antibody tests), and ex-infected (with gastric mucosal atrophy and negative infection tests, except for antibody tests). The optimal criteria with combined use of the PG II concentrations and the PG I/PG II ratio were investigated separately for PG measurements obtained with the chemiluminescent magnetic particle immunoassay (CLIA) and latex agglutination (LA) methods, such that the specificity was greater than 70% and the sensitivity was no less than 95% among the never-infected and infected subjects. Similar analyses were performed by combining the data from ex-infected and infected subjects. Results For the CLIA (LA) method, the optimal criterion among 349 (397) never-infected and 748 (863) infected subjects was a PG II value of at least 10 (12) ng/mL or a PG I/PG II ratio no more than 5.0 (4.0), which produced 96.3% (95.1%) sensitivity and 82.8% (72.8%) specificity. When 172 (236) ex-infected subjects were included, the optimal criterion was the same, and the sensitivity was 89.1% (86.9%). Conclusions The above criteria may be practical for clinical use, and PG tests using these criteria might prevent unnecessary endoscopic examinations for never-infected subjects.

AimsSecreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodelling.Methods and resultsAdipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Adipolin deficiency also led to a reduction in transforming growth factor-β (TGF-β) 1 protein levels in injured arteries. Treatment of cultured macrophages with adipolin protein led to a reduction in lipopolysaccharide-stimulated expression of inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin (IL) 6, and monocyte chemotactic protein (MCP)-1. These effects were reversed by inhibition of TGF-β receptor II (TGF-βRII)/Smad2 signalling. Adipolin also reduced platelet-derived growth factor (PDGF)-BB-stimulated proliferation of vascular smooth muscle cells (VSMCs) through a TGF-βRII/Smad2-dependent pathway. Furthermore, adipolin treatment significantly increased TGF-β1 concentration in media from cultured VSMCs and macrophages.ConclusionThese data indicate that adipolin protects against the development of pathological vascular remodelling by attenuating macrophage inflammatory responses and VSMC proliferation.

Objective Rectal lymphoid follicular aphthous (LFA) lesions are related to ulcerative colitis (UC) and can be initial lesions of UC. We investigated the clinical course and prognosis of rectal LFA lesions. Methods This is a retrospective analysis of the clinical records at a single center. Patients Thirteen consecutive cases with LFA lesions treated at Hiroshima University Hospital between 1998 and 2015 were evaluated. Another 49 consecutive cases with ulcerative proctitis treated in the same period were enrolled as the control group. The clinical course and prognosis of both groups were evaluated. Results The group with LFA lesions included 9 women and 4 men with a median age of 39.9 years (range, 21-70 years). A total of 11 cases progressed to typical UC at 5-51 months. Proximal extension of these typical UC lesions was observed in 7 (53.8%) cases, which was significantly higher than in the control group (10 cases, 20.8%). Three cases (5-year accumulation incidence rate, 27.3%) progressed to steroid-intractable UC, a significantly higher incidence than that of the control group (3 cases; 5-year accumulation incidence rate, 6.9%). Conclusion Rectal LFA lesions frequently progress to typical UC with proximal extension, some of which become intractable to corticosteroid treatment.

Background and Aim: The incidence of gastric cancer occurring after successful Helicobacter pylori eradication has been increasing. We aimed to clarify the influence of eradication therapy on the ability to diagnose early gastric cancer after successful H. pylori eradication in patients who underwent annual endoscopic screening. Methods: A total of 220 patients (179 men; mean age 71.0 years) had differentiated-type early gastric cancer that was discovered through annual endoscopic screening. Patients were categorized into 2 groups: the H. pylori-eradicated group (n = 81) and the non-eradicated control group (n = 139). After matching patients by propensity scores, we retrospectively analyzed the clinicopathological characteristics of 162 patients (81 patients in each group). Furthermore, we compared the characteristics of gastric cancer with submucosal invasion between the 2 groups. Results: The prevalence of early gastric cancer with submucosal invasion was significantly higher in the eradicated group than in the control group, both before propensity score matching (16.0 vs. 7.2%, respectively; p = 0.038) and after propensity score matching of 81 pairs (16.0 vs. 4.9%, respectively; p = 0.021). In the comparative analysis of gastric cancer with submucosal invasion, there was no difference between the 2 groups with respect to factors influencing the ability to diagnose its presence endoscopically. Conclusion: H. pylori eradication therapy increased the prevalence of differentiated-type gastric cancer with submucosal invasion despite patients’ completion of annual endoscopic screening after eradication.

To minimize motion-related distortion of reconstructed images, conventional positron emission tomography (PET) measurements of the brain inevitably require a firm and tight head restraint. While such a restraint is now a routine procedure in brain imaging, the physiological and psychological consequences resulting from the restraint have not been elucidated. To address this problem, we developed a restraint-free brain PET system and conducted PET scans under both restrained and non-restrained conditions. We examined whether head restraint during PET scans could alter brain activities such as regional cerebral blood flow (rCBF) and dopamine release along with psychological stress related to head restraint. Under both conditions, 20 healthy male participants underwent [15O]H2O and [11C]Raclopride PET scans during working memory tasks with the same PET system. Before, during, and after each PET scan, we measured physiological and psychological stress responses, including the State-Trait Anxiety Inventory (STAI) scores. Analysis of the [15O]H2O-PET data revealed higher rCBF in regions such as the parahippocampus in the restrained condition. We found the binding potential (BPND) of [11C]Raclopride in the putamen was significantly reduced in the restrained condition, which reflects an increase in dopamine release. Moreover, the restraint-induced change in BPND was correlated with a shift in the state anxiety score of the STAI, indicating that less anxiety accompanied smaller dopamine release. These results suggest that the stress from head restraint could cause unsolicited responses in brain physiology and emotional states. The restraint-free imaging system may thus be a key enabling technology for the natural depiction of the mind.

Background Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients. Methods Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing. Results H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples. Conclusions Some SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.

Endodermal cyst (EC) is a benign tumor that can arise along the craniospinal axis. Infrequently, ECs undergo malignant transformation. A 43-year-old man presented with numbness in the right arm, leg and occipitalgia. MRI revealed a multicystic, intradural extramedullary tumor at C2 with enhancement along the ventral surface of the spinal cord. Blood test showed an abnormal increase in serum carbohydrate antigen 19-9 (CA 19-9) level. Systemic positron emission tomography-computed tomography was normal. He underwent total tumor resection and was diagnosed with EC. He developed double vision, hearing loss, and swallowing difficulty on postoperative day 70. Cerebral MRI revealed marked extensions of leptomeningeal dissemination. The serum CA 19-9 level increased continuously and finally reached 1515.0 U/ml. He died of respiratory failure on day 108. An autopsy did not reveal abnormalities in the abdominal and chest organs. On microscopic examination, the post-mortem specimen revealed adenocarcinoma. Immunohistochemically, both the surgical and autopsy specimens were positive for CA 19-9. Spinal ECs may lead to malignant transformation with leptomeningeal dissemination that causes abnormal elevation of serum CA 19-9 levels.

Background and aim Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation, and hepatocellular injury with varying degrees of fibrosis. There are currently no established treatment approaches for NASH other than lifestyle interventions. Periostin, a matricellular protein required for tissue remodeling and fibrosis, plays an important role in hepatic steatosis and fibrosis and could be a potential target for NASH treatment. Advances in molecular biology and biochemical engineering have led to the development of antisense oligonucleotides (ASOs) that can inhibit target genes with no significant toxic effects. Herein, we investigated the therapeutic effects of periostin-targeting ASO (PNASO) in NASH. Methods C57BL/6J mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) to induce NASH with or without intraperitoneal injection of mouse PNASO. To explore the role of periostin in hepatocellular steatosis, Hc3716 cells, an immortalized human hepatocyte line, were treated with recombinant periostin in vitro. Results The induced periostin expression in the liver of CDAHFD-fed mice was significantly suppressed by PNASO. The deletion of hepatic periostin by PNASO significantly ameliorated hepatic steatosis while restoring the expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α) and its target genes. PNASO also inhibited hepatic fibrosis, reflected by the reduction of alpha-smooth muscle actin, collagen type I, and other fibrotic markers. In vitro experiments demonstrated that treatment with recombinant periostin increased cellular lipid accumulation in Hc3716 cells accompanied with the downregulation of PPAR-α. Conclusions Periostin-targeting ASO is a potential therapeutic approach for the efficient treatment of hepatic steatosis and fibrosis in NASH.

Background and Aim: Reddish depressed lesions (RDLs) frequently observed in patients following Helicobacter pylori eradication are indistinguishable from gastric cancer. We examined the clinical and histological feature of RDLs and its relevant endoscopic diagnosis including magnifying narrow-band imaging (M-NBI). Methods: We enrolled 301 consecutive patients with H. pylori eradication who underwent endoscopy using white light imaging (WLI). We examined the prevalence and host factors contributing to the presence of RDLs. Next, we used M-NBI in 90 patients (104 RDLs), and compared the diagnostic efficacy between M-NBI and WLI groups using propensity-score matching analysis. Results: In 301 patients after eradication, 117 (39%) showed RDLs. Male, open-type atrophy, and gastric cancer history were risk factors for RDLs. A gastric biopsy was needed in 83 (71%) during WLI observation and only 2 were diagnosed with adenocarcinoma. In M-NBI group, a biopsy was performed in 21 (20%), and 9 were diagnosed with adenocarcinoma. A biopsy was required in fewer patients, and the positive predictive value of a biopsy was statistically higher in M-NBI than in the WLI group (p < 0.01). Conclusions: RDLs are frequently observed in high-risk patients for gastric cancer after eradication. M-NBI demonstrated significantly superior diagnostic efficacy with respect to RDL.

Many studies have evaluated surgical treatments for spinal deformities in patients with neuromuscular disease. However, few reports have described patients with Fukuyama congenital muscular dystrophy (FCMD). A 13-year-old boy with FCMD was unable to sit for long periods or sleep in the supine position because of progressive scoliosis. His Cobb angle worsened from 27° to 41° in 5months. He underwent standard posterior spinal fusion and pedicle-screw-alone fixation from T5 to S1. Postoperatively, his Cobb angle improved from 41° to 25° without exacerbation for 2years. After the surgery, he was able to sit for longer periods without pain, and he and his family were satisfied with the efficacy of the spinal fusion. Some patients with mild FCMD can sit at the age of puberty, but progression to scoliosis is possible. Therefore, spinal fusion for progressive scoliosis in patients with FCMD should be considered.

Purpura nephritis and autosomal dominant polycystic kidney disease are relatively rare kidney disorders. We present a case complicated by these two diseases. A 68 year-old man with polycystic kidney disease was referred to our hospital with a high fever lasting 3 days and pyuria. Pyelonephritis was suspected based on computed tomography findings of bilateral swelling of the kidney. Inflammation subsided gradually after the initiation of antimicrobial therapy. However, approximately 3 weeks later, the patient developed a fever and skin purpura on the extremities, stomach colic pain, gross hematuria, and increased proteinuria was evident. Therefore, we diagnosed Henoch-Schönlein purpura complicated with nephritis based on biopsies of the skin and the kidney. Immunosuppressant therapy was administered; every symptom was relieved and proteinuria decreased for approximately 20 months.

It is clinically important to diagnose drug-induced gastric lesions correctly. Recently, the use of proton pump inhibitors (PPI) has increased worldwide. The histological features induced by PPI have been reported; however, few reports have described endoscopic findings induced by PPI. Therefore, we aimed to clarify the characteristic endoscopic features in PPI users and associated pathogenic factors.We prospectively registered 1007 consecutive participants (70 PPI users and 937 nonusers) who underwent endoscopic examination for cancer screening in three hospitals/clinics. Clinical data and endoscopic findings were recorded in the registration forms. We compared the endoscopic features between the two groups and evaluated contributing factors via univariate and multivariate analyses.Multiple white elevated lesions (MWEL) and cobblestone-like mucosa (CLM) were more commonly observed in PPI users compared with nonusers (p .01). Foveolar hyperplastic polyps were also frequently observed in PPI users but were not statistically significantly different (p = .06). MWEL and CLM were more frequently observed in older patients than in younger patients. MWEL was more frequently observed in female patients than in male patients; however, CLM was predominantly observed in male patients.MWEL and CLM are characteristic endoscopic features in PPI users. A gender-associated difference was noted in terms of the frequency of these lesions.

Background and aims Obesity contributes to the progression of vascular disorders. C1q/TNF-related protein (CTRP) 1 is a circulating adipokine, which is upregulated in obese complications including coronary artery disease. Here, we investigated the role of CTRP1 in regulation of vascular remodeling after mechanical injury and evaluated its potential mechanism. Methods Mice were subjected to wire-induced injury of left femoral arteries. An adenoviral vector encoding CTRP1 (Ad-CTRP1) or β-galactosidase as a control was injected into the jugular vein of mice 3 days prior to surgery. Results Systemic administration of Ad-CTRP1 to wild-type mice led to reduction of the neointimal thickening after wire-induced arterial injury and the number of bromodeoxyuridine-positive cells in injured vessels as compared with treatment with control vectors. Treatment of vascular smooth muscle cells (VSMCs) with CTRP1 protein attenuated proliferative activity and ERK phosphorylation in response to PDGF-BB. CTRP1 treatment increased cyclic AMP (cAMP) levels in VSMCs, and inhibition of adenylyl cyclase reversed the inhibitory effect of CTRP1 on VSMC growth and ERK phosphorylation. Antagonization of sphingosine-1-phosphaterote (S1P) receptor 2 blocked the effects of CTRP1 on cAMP production and VSMC growth. Furthermore, CTRP1-knockout mice had enhanced neointimal thickening following injury and increased numbers of proliferating cells in neointima compared to control WT mice. Conclusions These findings indicate that CTRP1 functions to prevent the development of pathological vascular remodeling by reducing VSMC growth through the cAMP-dependent pathway.

Backgrounds and Aims: The serological risk-prediction system combined the pepsinogen (PG) test, and anti-Helicobacter pylori antibody is available for evaluation of gastric cancer risk. In this system, chronic atrophic gastritis (CAG) or H. pylori infection is diagnosed. Subjects with H. pylori negative and PG test negative (group A) are supposed to be those who have never been infected with H. pylori and are at extremely low risk for gastric cancer. However, a certain proportion of patients with CAG has been identified as the extremely low-risk group (group A). Here we examined endoscopic atrophy and investigated its relationship with the ABC classification system. Methods: We examined 540 patients. All patients underwent an endoscopic examination for evaluating corpus atrophy. Fasting sera were collected and serum PGs and anti-H. pylori antibody (Hp-Ab) titer (E-plate Eiken) were evaluated. Results: Of the 540 patients, 306 were classified into group A. However, 136 of them showed signs of endoscopic atrophy (group A with CAG). Group A with CAG frequently comprised the elderly. A new titer cut-off (Conclusion: The prevalence of group A with CAG patients is a critical problem, especially in elderly subjects.

Objective The aim of the present study is to assess the difference in the detection rates of small-bowel lesions in chronic abdominal pain (CAP) patients with irritable bowel syndrome (IBS) and non-IBS. Patients Ninety-nine CAP patients who were scheduled to undergo capsule endoscopy (CE) to investigate their abdominal symptoms were included in this study. Among the subjects, 34 patients fulfilled the Rome III criteria for IBS (IBS group); the remaining 65 patients were categorized as the non-IBS group. CE was performed in both groups and the total enteroscopy achievement rate, small-bowel lesion detection rate, and the presence of small-bowel lesions were evaluated. We also evaluated the patients' blood test results and the rate at which abdominal symptoms improved following internal medication. Results Total enteroscopy was achieved in 62% (21/34) and 86% (56/65) of the IBS and non-IBS patients, respectively. The total enteroscopy achievement rate was significantly higher in non-IBS patients. The small-bowel lesion detection rates were 3% (1/34) and 19% (12/65), respectively, and the detection rate was significantly higher in the non-IBS patients. In the non-IBS patients, mean C-reactive protein (CRP) was significantly higher in the patients with small-bowel lesions. The abdominal symptoms of 12 (92%) of the CAP patients with small-bowel lesions were improved by internal medication. Conclusion CE may be considered for non-IBS CAP patients with high levels of CRP.

The serological risk prediction system combines the pepsinogen test and anti-Helicobacter pylori (H. pylori) antibody determination. In this system, chronic atrophic gastritis (CAG) is diagnosed using the pepsinogen test. Patients who are H. pylori negative and pepsinogen negative are classified into group A, are assumed to be H. pylori uninfected, and are at an extremely low risk for gastric cancer. However, gastric cancers are detected in this group. The aim of this study is to clarify the clinicopathological status of group A patients with gastric cancer. A total of 109 gastric cancer patients classified as group A were enrolled in a multicenter study. Group A patients were divided into two subgroups: group AN (H. pylori uninfected) and group AP (H. pylori infected). They were compared to 183 H. pylori-infected gastric cancer patients who were not in group A. Of the 109 patients, only 7 were classified as group AN; the other 102 were classified as group AP. The clinicopathological features of group AP included older age, predominantly differentiated type cancer, endoscopically visualized CAG, and pepsinogen (PG) I/II ratio lower than that of group AN. In group AN, the depressed type was dominant, and the PG I/II ratio was higher than in those gastric cancer patients who were infected with H. pylori. Patients in group AP had CAG, and their gastric cancers were similar to those of H. pylori-eradicated patients. Concerning the recent ABC classification system, advanced decision criteria should be proposed to decrease the false-negative evaluation of gastric cancer risk.

A 57-year-old woman sustained gradually progressive sensorimotor disturbance in the left upper extremity for one year. Neurological examination found a diminished sensation below the left C7 dermatome and reduced strength in the left interosseous muscles. Computed tomography of the cervical spine revealed a high density mass at C7, in the left dorsal part of the spinal canal. Magnetic resonance imaging found an enhancing, en-plaque tumor at C6-T1, involving a non-enhancing part, and considerable compression of the spinal cord. The patient underwent tumor resection through hemilaminectomy of C5-C7. The tumor was located epidurally, highly fibrous including bony-hard parts, and severely adhered to the dura mater that necessitated drilling for debulking. A subtotal resection was achieved and histological diagnosis was a fibrous meningioma with metaplastic ossification. Ossification may be a pathognomonic appearance of spinal extradural meningiomas that makes resection maneuvers difficult.

The Japanese Respiratory Society 2017 guidelines strongly recommend switching from intravenous (IV) to oral antibiotics in patients with community-acquired pneumonia (CAP), following improvement in clinical symptoms and laboratory findings. Here, we retrospectively investigated the real-world, nationwide treatment and switching patterns for hospitalized patients with CAP in Japan using administrative data from 372 Japanese Diagnosis Procedure Combination hospitals from April 2010 to December 2018. Hospitalizations for CAP (patient age ≥20 years) with an A-DROP classification for CAP severity and IV antibiotics initiated on the admission date were included. Overall, 210,314 hospitalizations (moderate CAP: 61.7%) in 183,607 patients were analyzed. The median (interquartile range [IQR]) age at admission was 79 (70–86) years. Penicillin (51.9%) and cephalosporin (38.9%) were the most common IV antibiotic classes used and the median (IQR) duration of IV use was 8 (6–11) days. Switching to oral antibiotics during a hospitalization occurred in 30.1% (n = 63,311) of patients after a median (IQR) of 7 (5–10) days of IV treatment. The most frequently used oral antibiotic classes after a switch were fluoroquinolone (45.9%) and penicillin (24.8%). The switch rate was higher among hospitalizations with milder CAP, in respiratory medicine ward and in larger hospitals. The overall switch rates did not change over the study period. The findings from this analysis suggest that early switch from IV to oral antibiotics was not widely implemented during the 8 years of the study period. Further observation will be needed to see the potential impact of the guidelines update in 2017 in Japan.

Attenuation correction is imperative in positron emission tomography (PET) measurements. A traditional transmission scan with an external positron line source has been replaced by X-ray CT or MRI. However, the scanner’s mechanics increases cost and these additional scans sometimes accompany image displacement which makes final images degraded in quality. Therefore, in this study, to overcome these problems, we propose an attenuation correction framework that generates transmission images from uncorrected emission images for brain PET imaging using deep convolutional neural networks (CNN). The advantage of this study is that an estimated transmission image is applicable in PET measurements with various types of ligands. Using encoder– decoder-based CNNs, the transmission scans for attenuation correction are generated from the uncorrected emission scans. We used the brain PET datasets from 1030 patients scanned with the following PET ligands: 18F-FDG, 18F-BCPP-EF, 11C-Racropride, 11C-PIB, 11C-DPA-713, and 11C-PBB3. We randomly selected 20% of the datasets as the testing dataset, and used the remaining 80% to train the network. As a result, the CNN generated was less noisy and had more uniform transmission scans compared to the original transmission scans (using a 68Ge-68Ga rotation line source). The CNN showed the peak signal-to-noise ratio and structural similarity indices as being 31.5 ± 1.8 dB and 0.80 ± 0.02 in generated and original transmission images of many types of PET ligands, respectively. These results indicate that the proposed CNN-based framework allows accurate attenuation correction in brain PET system using different types of PET ligands.

Background/Aims: Dual red imaging (DRI) is a new, image-enhanced endoscopy technique. There are few reports about the usefulness of DRI during gastric endoscopic submucosal dissection (ESD). We aimed to examine the usefulness of DRI in endoscopic hemostasis during gastric ESD. Methods: We enrolled a total of 20 consecutive patients who underwent gastric ESD. Five endoscopists compared DRI with white light imaging (WLI) for the visibility of blood vessels and bleeding points while performing endoscopic hemostasis. Results: The visibility of blood vessels was increased in 56% (19/34) of the cases, and the visibility of bleeding points was improved in 55% (11/20) of the cases with the use of DRI compared with the use of WLI. Conclusions: DRI improved the visibility of blood vessels and bleeding points in cases with oozing bleeding, blood pooling around the bleeding points, and multiple bleeding points. Clin Endosc 2020;53:54-59

An epidermoid cyst is an infrequent entity among cysts found in the presacral region, frequently coexistent with a meningocele. Diffusion-weighted imaging is known to be a useful diagnostic measure for differentiating presacral epidermoid cysts. Here, we present a large but asymptomatic case found in the presacral region. Epidermoid cysts should be considered in patients with presacral cysts.

Rationale: Physical exercise provides benefits for various organ systems, and some of systemic effects of exercise are mediated through modulation of muscle-derived secreted factors, also known as myokines. Myonectin/C1q (complement component 1q)/TNF (tumor necrosis factor)-related protein 15/erythroferrone is a myokine that is upregulated in skeletal muscle and blood by exercise. Objective: We investigated the role of myonectin in myocardial ischemic injury. Methods and Results: Ischemia-reperfusion in myonectin-knockout mice led to enhancement of myocardial infarct size, cardiac dysfunction, apoptosis, and proinflammatory gene expression compared with wild-type mice. Conversely, transgenic overexpression of myonectin in skeletal muscle reduced myocardial damage after ischemia-reperfusion. Treadmill exercise increased circulating myonectin levels in wild-type mice, and it reduced infarct size after ischemia-reperfusion in wild-type mice, but not in myonectin-knockout mice. Treatment of cultured cardiomyocytes with myonectin protein attenuated hypoxia/reoxygenation-induced apoptosis via S1P (sphingosine-1-phosphate)-dependent activation of cAMP/Akt cascades. Similarly, myonectin suppressed inflammatory response to lipopolysaccharide in cultured macrophages through the S1P/cAMP/Akt-dependent signaling pathway. Moreover, blockade of S1P-dependent pathway reversed myonectin-mediated reduction of myocardial infarct size in mice after ischemia-reperfusion. Conclusions: These data indicate that myonectin functions as an endurance exercise-induced myokine which ameliorates acute myocardial ischemic injury by suppressing apoptosis and inflammation in the heart, suggesting that myonectin mediates some of the beneficial actions of exercise on cardiovascular health.

Summary Background Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. Methods In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response—ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)—according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Findings Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19–179, range 2–882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). Interpretation Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.

The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.

In the original publication of the article, the article title was published with typo. The word "eradiation" should be "eradication" in the article title and keywords.

Primary malignant melanoma of the esophagus (PMME) is rare but aggressive. PMME accounts for approximately 0. 1% of all malignant esophageal neoplasms occurring worldwide, and is usually diagnosed during the advanced stage. A 67-year-old man underwent an esophagogastroduodenoscopy (EGD) at our hospital and confirmed 20 mm of black pigmentation in the lower esophagus in the chest area. Pathological biopsy findings of the black-pigmented epithelial tissue revealed the presence of tumor cells with brown granules, leading to the diagnosis of malignant melanoma. Owing to difficulty in accurately diagnosing the range in this PMME case, we performed thoracoscopic esophagectomy. Pathological organisation test results were pT1a-LPM, INFb, pN0, and pM0, which were diagnosed at pStage I. The lesion expanded extensively, measuring > 10 cm in diameter. The tumor cells, which were centrally located in the black-pigmented area, were observed to have proliferated beyond the surrounding brownish area into the mucosa, but no findings were found in the endoscopic examination. As in this case, because PMME may diffusely spread along the basal layer outside the range of pigmentation, endoscopic diagnosis of the extent of disease spread may be impossible; hence, it is important to keep this phenomenon in mind while performing resection to treat PMME.

Obesity is associated with an increased risk of cardiovascular disease. C1q/TNF-related protein (CTRP)-1 is a poorly characterized adipokine that is up-regulated in association with ischemic heart disease. We investigated the role of CTRP1 in myocardial ischemia injury. CTRP1-knockout mice showed increased myocardial infarct size, cardiomyocyte apoptosis, and proinflammatory gene expression after I/R compared with wild-type (WT) mice. In contrast, systemic delivery of CTRP1 attenuated myocardial damage after I/R in WT mice. Treatment of cardiomyocytes with CTRP1 led to reduction of hypoxia-reoxygenation-induced apoptosis and lipopolysaccharide-stimulated expression of proinflammatory cytokines, which was reversed by inhibition of sphingosine-1-phosphate (S1P) signaling. Treatment of cardiomyocytes with CTRP1 also resulted in the increased production of cAMP, which was blocked by suppression of S1P signaling. The antiapoptotic and anti-inflammatory actions of CTRP1 were cancelled by inhibition of adenylyl cyclase or knockdown of adiponectin receptor 1. Furthermore, blockade of S1P signaling reversed CTRP1-mediated inhibition of myocardial infarct size, apoptosis, and inflammation after I/R in vivo. These data indicate that CTRP1 protects against myocardial ischemic injury by reducing apoptosis and inflammatory response through activation of the S1P/cAMP signaling pathways in cardiomyocytes, suggesting that CTRP1 plays a crucial role in the pathogenesis of ischemic heart disease.

Background and Aim Gastric cancer develops due to atrophic gastritis induced by Helicobacter pylori (H. pylori) infection. Serum levels of pepsinogen (PG) are known to be excellent markers for evaluating the degree of atrophic gastritis. We investigated whether chronic gastritis could be diagnosed by evaluating serum PG levels. Methods A total of 4483 patients (average age, 49.7 years; 2879 men) were included in this study. Fasting serum samples were collected and anti-H. pylori antibody and PG levels were evaluated. We evaluated the endoscopic atrophy grade or histological extent of gastritis, and calculated the diagnostic capability of this serum marker. Results A total of 4483 patients, were diagnosed as being positive (4160) or negative (323) for H. pylori-induced gastritis. In patients with H. pylori-induced gastritis, the PG II levels were higher and the PG I/II ratios were lower than among those without H. pylori gastritis. A cut-off values of (i) PG I/II ≤ 5; (ii) PG II ≥ 10 or PG I/II ≤ 5; (iii) PG II ≥ 12 or PG I/II ≤ 4.5 showed high sensitivity and accuracy (over 90%) for diagnosing H. pylori-induced gastritis. Moreover, in a mass screening of healthy subjects, a cut-off value of PG I/II ≤ 4.5 might be better for diagnosing the presence of gastritis because of a sensitivity and specificity > 80%. Conclusions The presence of H. pylori-induced gastritis can be evaluated using serum PG levels.

The aim of this study was to quantitatively evaluate the function of the cranial diploic and spinal epidural veins as cerebrospinal fluid (CSF) drainage pathways by measuring lipocalin-type prostaglandin D synthase (PGDS) and cystatin C (CysC) dissolved in the blood of these veins. This was a prospective study involving 51 consecutive patients, 31 males and 20 females, who underwent 41 cranial and 10 spinal surgeries. Intraoperatively, peripheral venous blood and diploic venous blood, or peripheral venous blood and spinal epidural venous blood samples were simultaneously collected and immediately centrifuged. For all samples, dissolved albumin (for reference), PGDS and CysC were measured using an enzyme-linked immunosorbent assay. The diploic vein/peripheral vein ratios in five cranial locations and epidural vein/peripheral vein ratios were calculated and statistically evaluated for the three biomarkers. For PGDS, the diploic vein/peripheral vein ratio was significantly increased in the frontal (P = 0.011), temporal (P = 0.028), parietal (P = 0.046) and skull base (P = 0.039), while it did not reach statistical significance for CysC. For patients older than 45 years, the diploic vein/peripheral vein ratio for PGDS was significantly decreased in the frontal region (P = 0.028), and the epidural vein/peripheral vein ratio for CysC was significantly decreased (P = 0.014). These results show that the diploic veins constitute CSF drainage pathways with heterogeneous functional intensity at different cranial locations. Compared with the diploic veins, spinal epidural veins seem to drain less CSF. The cranial diploic and spinal epidural veins may jointly function as an alternative, age-related trans-dural CSF drainage system.

Background— Myocardial infarction (MI) is one of the major causes of death worldwide. Chronic heart failure is a serious complication of MI that leads to poor prognosis. We recently found that neuron-derived neurotrophic factor (NDNF) is a proangiogenic secretory protein that is upregulated in ischemic skeletal muscle. Here, we examined whether NDNF modulates cardiac remodeling in response to chronic ischemia. Methods and Results— C57BL/6J wild-type mice were subjected to the permanent ligation of the left anterior descending coronary artery to create MI. Adenoviral vectors expressing NDNF or β-galactosidase (control) were intramuscularly injected into mice 3 days before permanent left anterior descending coronary artery ligation. Intramuscular administration of adenoviral vectors expressing NDNF to mice resulted in increased levels of circulating NDNF. Adenoviral vectors expressing NDNF administration improved left ventricular systolic dysfunction and dilatation after MI surgery. Moreover, adenoviral vectors expressing NDNF enhanced capillary formation and reduced cardiomyocyte apoptosis and hypertrophy in the post-MI hearts. Treatment of cultured cardiomyocytes with recombinant NDNF protein led to reduced apoptosis under conditions of hypoxia. NDNF also promoted the phosphorylation of Akt and focal adhesion kinase in cardiomyocytes. Blockade of focal adhesion kinase activation blocked the stimulatory effects of NDNF on cardiomyocyte survival and Akt phosphorylation. Similarly, treatment of cultured endothelial cells with NDNF protein led to enhancement of network formation and Akt phosphorylation, which was diminished by focal adhesion kinase inhibition. Conclusions— These data suggest that NDNF ameliorates adverse myocardial remodeling after MI by its abilities to enhance myocyte survival and angiogenesis in the heart through focal adhesion kinase/Akt-dependent mechanisms.