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Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure.We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms.The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small- and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the double-blind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p 0.01) and significant decrease in transepidermal water loss (p 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group.The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

We report about a patient with an extremely rare long-segment Barrett’s esophagus (LSBE) who developed extensive superficial adenocarcinoma and underwent radical (R0) resection based on an accurate preoperative diagnosis of tumor extent. A 68-year-old man with no subjective symptoms and no noteworthy medical history was diagnosed with adenocarcinoma after a biopsy of a protruding lesion in the lower esophagus. Narrow-band imaging (NBI) magnification endoscopy revealed that the protruded lesion was within the LSBE, and a flatly extended superficial esophageal adenocarcinoma (SEAC) was observed proximal to the protruded lesion. After confirming the extent of the tumorous lesion via endoscopic biopsy, subcircumferential endoscopic submucosal dissection (ESD) was performed for the extensive tumor, which resulted in a histological R0 resection. Prophylactic steroid therapy was performed to prevent refractory post-ESD stenosis. There was no residual tumor or recurrence of the cancer, and the patient’s postoperative course was favorable. Preoperative diagnosis of tumor extent using NBI magnification endoscopy may therefore be useful for characterizing SEAC occurring in the LSBE, given that detecting the presence and determining the extent of these tumors is normally difficult. Prophylactic therapy with local steroid injection can prevent refractory stenosis after quite extensive ESDs for SEACs in the LSBE.

BACKGROUND Esophageal adenocarcinoma (EAC) derived from long-segment Barrett’s esophagus (LSBE) is extremely rare in Asia. LSBE-related EAC is often difficult to diagnose in the horizontal extent. If the tumor has spread throughout the LSBE, whole circumferential endoscopic submucosal dissection (ESD) should be performed, which is difficult to complete safely. Additionally, whole circumferential ESD can bring refractory postoperative stenosis. We hereby report a case of EAC involving the whole circumference of the LSBE, achieving complete endoscopic removal without complications. CASE SUMMARY An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy. We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE (C 3.5, M 4.0) using narrow-band imaging magnification endoscopy (NBI-M). We achieved circumferential en bloc resection of the lesion safely with special ESD techniques. Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE, and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin. To prevent post-ESD stenosis, we performed endoscopic local injection of steroids, followed by oral administration of steroids. There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD. In summary, we experienced a rare case of LSBE-related EAC. The horizontal tumor extent was accurately diagnosed by NBI-M. Additionally, we achieve whole circumferential ESD safely without postoperative refractory stenosis. CONCLUSION NBI-M, ESD, and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis.

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.

A man in his 60s visited a clinic with chief complaints of a fever and general malaise. Suspecting a liver abscess in the left lobe with infiltration into the subcutaneous fat tissue under the rectus abdominis muscle based on computed tomography findings, we performed fine-needle aspiration. An amoebic liver abscess was diagnosed. Remission was achieved by the oral administration of metronidazole alone without placement of a drainage tube. The results obtained in this case suggest that the first line of treatment should be a non-invasive approach with oral administration alone. Invasive intervention should then be considered depending on subsequent progress.

AIM This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P

Most cases of Dieulafoy's lesion, a rare cause of upper gastrointestinal bleeding, occur in the upper gastric corpus, usually with no edematous bulging or fold convergence around the mucosal defect. This report describes a case of Dieulafoy's lesion with subepithelial lesion (SEL)-like morphology. Endoscopic treatment by hemoclipping was difficult. Because of repeated bleeding, abdominal dynamic contrast computed tomography (CT) was conducted. Results showed a large caliber, tortuous artery branching directly from the celiac artery and feeding into the gastric wall of the gastric fundus. Rupture of this vessel in the submucosa was thought to be responsible for the SEL-like morphology. All findings indicated endoscopic treatment from the gastric mucosal side was too difficult. Therefore, we treated the lesion using interventional radiology (IR) technique of vascular embolization. If an SEL-like Dieulafoy's lesion cannot be treated by endoscopic hemostasis, then IR might be necessary to treat the vascular anomaly.

Introduction: Hematochezia is observed frequently in daily practice. However, natural hemostasis often prevents identification of the bleeding source during observations. This study was conducted to clarify risk factors related to rebleeding in hematochezia patients without an identified cause of bleeding. Methods: We analyzed patients who were admitted to Dokkyo Medical University Hospital during April 1, 2009, through March 31, 2015, with the chief complaint of hematochezia. Main outcome measures included the rebleeding rate and the period until rebleeding in hematochezia patients without an identified bleeding source. Results: We selected 159 patients for analyses. Rebleeding was observed in 46 (28.9%) of 159 patients. The median period until first rebleeding was 166 days (2–3,046 days). Univariate analysis indicated that risk factors for rebleeding were male gender (p = 0.029), higher age (p = 0.023), antithrombotic medicines (p = 0.047), lower hemoglobin on admission (p = 0.024), and the presence of diverticula (p = 0.002). Multivariate analysis indicated the presence of diverticula (p = 0.023) and male gender (p = 0.043) as rebleeding risk factors. Discussion/Conclusion: In patients with hematochezia of unknown origin, risk factors for rebleeding indicated in this study, especially the presence of diverticula and male gender, should be given particular attention by physicians.

The Mayo endoscopic subscore (MES) is a major endoscopic scoring system used to assign a status of mucosal inflammation and disease activity to patients with ulcerative colitis (UC). Using interobserver reliability (IOR), this study clarified the difficulties for endoscopic observers imposed by MES parameters used for the endoscopic evaluation of UC in histological remission. First, 42 endoscopists of four observer groups examined each MES parameter, which were evaluated from endoscopically obtained images of 100 cases as Grade 0 or 1 of the Nancy histological index of histopathological inflammation. Then, IOR was assessed using multiple κ statistics for each finding of MES. The results showed that IOR among all the observers was slight or fair for all the parameters, indicating a low IOR. The experts of the UC practice group had “moderate” or higher IOR for seven of the nine parameters, whereas “slight” or “fair” results were found for all parameters by the trainee group. The IOR for each MES parameter was calculated separately for the observer groups. All the groups showed “slight” or “fair” for “Erythema” and “Decreased vascular pattern”. Large differences between the endoscopists were found in the IOR for the MES parameters in UC in histological remission. Even among UC practice experts, the IOR was low for “Erythema” and “Decreased vascular pattern”.

Pulmonary lepidic metastasis from intraductal papillary mucinous carcinoma (IPMC) of the pancreas is extremely rare. The patient was a 50s-year old male who was hospitalized in the department of respiratory in our hospital for the evaluation of ground-glass opacities in both lungs on computed tomography (CT) imaging. Steroid therapy was administered, as interstitial pneumonia was suggested; however, there was no improvement. A transbronchial lung biopsy (TBLB) revealed the possibility of distant lung metastases. Abdominal CT revealed pancreatic cystic lesions; the patient was, therefore, referred to our department for further evaluation. Endoscopic ultrasound revealed large multi-cystic lesion with mural nodule and wall thickness. A subsequent pancreatic juice cytology under endoscopic retrograde cholangiopancreatography revealed adenocarcinoma. As this was consistent with the pathological findings shown on TBLB, IPMC metastasis to the lung was diagnosed. In this case, it was considered that pulmonary lepidic metastasis from IPMC by CT imaging and pathological findings. Although the cases of pulmonary lepidic metastasis from gastrointestinal cancer are rare, we should consider these pathological conditions when pneumonia-like infiltration observed on imaging studies does not respond to treatment.

Ultrasonographic elastography is a modality used to visualize the elastic properties of tissues. Technological advances in ultrasound equipment have supported the evaluation of elastography (EG) in endosonography (EUS). Currently, the usefulness of not only EUS-strain elastography (EUS-SE) but also EUS-shear wave elastography (EUS-SWE) has been reported. We reviewed the literature on the usefulness of EUS-EG for various diseases such as chronic pancreatitis, pancreatic solid lesion, autoimmune pancreatitis, lymph node, and gastrointestinal and subepithelial lesions. The importance of this new diagnostic parameter, “tissue elasticity” in clinical practice might be applied not only to the diagnosis of liver fibrosis but also to the elucidation of the pathogeneses of various gastrointestinal diseases, including pancreatic diseases, and to the evaluation of therapeutic effects. The most important feature of EUS-EG is that it is a non-invasive modality. This is an advantage not found in EUS-guided fine needle aspiration (EUS-FNA), which has made remarkable progress in the field of diagnostics in recent years. Further development of artificial intelligence (AI) is expected to improve the diagnostic performance of EUS-EG. Future research on EUS-EG is anticipated.

Immune checkpoint inhibitors (ICIs) increase T-cell activity and antitumor immune response. However, they also have immune-related adverse effects that can affect the gastrointestinal (GI) tract. A 62-year-old male patient who had undergone right lung upper lobectomy for adenocarcinoma of the lung received chemotherapy with pemetrexed sodium hydrate, carboplatin, and pembrolizumab to prevent postoperative recurrence of liver metastasis. However, the patient experienced severe diarrhea four months after the start of chemotherapy. Although a corticosteroid and two biological preparations were administered to alleviate the diarrhea, no improvement was observed. Eventually, remission was achieved when tacrolimus was administered. Treatment with corticosteroids is recommended for patients with GI adverse effects of ICIs. Rapid introduction of infliximab is necessary for refractory patients. Nevertheless, for refractory cases such as that of our patient, for whom even this regimen is inefficacious, tacrolimus might be recommended to induce remission as with cases of ulcerative colitis.

Success rates of balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) for patients with a reconstructed intestinal tract after surgical procedures are unsatisfactory. We retrospectively investigated the factors associated with unsuccessful BE-ERCP. Ninety-one patients who had a reconstructed intestinal tract after gastrectomy or choledochojejunostomy were enrolled. Age, sex, operative method, malignancy, endoscope type, endoscopist’s skill, emergency procedure, and time required to reach the papilla/anastomosis were examined. The primary endpoints were the factors associated with unsuccessful BE-ERCP selective cannulation, while the secondary endpoints were the rate of reaching the papilla/anastomosis, causes of failure to reach the papilla/anastomosis, cannulation success rate, procedure success rate, and rate of adverse events. Younger age (odds ratio, 0.832, 95% CI, 0.706–0.982, p = 0.001) and Roux-en-Y partial gastrectomy (odds ratio, 54.9, 95% CI, 1.09–2763, p = 0.045) were associated with unsuccessful BE- ERCP. The rate of reaching the papilla/anastomosis was 92.3%, the success rate of biliary duct cannulation was 90.5%, procedure success rate was 78.0%, and the rate of adverse events was 5.6%. In conclusion, Roux-en-Y partial gastrectomy and younger age were associated with unsuccessful BE-ERCP. If BE-ERCP is extremely difficult to perform in such patients after Roux-en-Y partial gastrectomy, alternative procedures should be considered early.

In 2009, diagnostic criteria for early chronic pancreatitis (DCECP2009) were proposed by the Japan Pancreas Society. This study aimed to evaluate the interobserver reliability (IOR) of endoscopic ultrasound (EUS) criteria for diagnosis of early chronic pancreatitis (ECP) between DCECP2009 and 2019 diagnostic criteria for ECP (DCECP2019) to assess the validity of the revision from the perspective of EUS findings. Among patients who underwent a detailed observation of the pancreas by EUS at our institution between January 2018 and March 2019, EUS images of 97 patients were extracted. Images were reviewed by 12 gastrointestinal endoscopy experts (eight pancreatologists, group A and four nonpancreatologists, group B). The overall kappa (K)-values for the IOR of the DCECP2009 EUS criteria were 0.424 and 0.563:0.231 for groups A:B, whereas the overall K-values for the DCECP2019 criteria were 0.618, and 0.733:0.442 for groups A:B. Regarding changes in the final diagnosis of ECP based on clinical features and EUS findings, 20 cases were definite ECP, 53 were probable ECP, and 24 were normal according to DCECP2009. In contrast, seven were definite ECP, 19 were probable ECP, and 71 were normal according to DECEP2019. IOR of DCECP2019 was higher than that of DCECP2009, which indicates an improvement in precision.

Red color sign-positive (RC-positive) esophageal varices present a high bleeding risk, necessitating prophylactic treatment. Among RC-positive esophageal varices, those classified morphologically as small straight varices (Form level 1: F1) are difficult to treat. Moreover, the appropriate time for therapeutic intervention remains undefined. This study assessed the bleeding risk in RC-positive F1 esophageal varices. After extracting 541 cases of F1 esophageal varices diagnosed during 1 January 2012–29 February 2020, 76 cases of RC-positive F1 esophageal varices were divided into two groups in terms of treatment intervention at diagnosis: 49 cases with (treatment group) and 27 cases without (follow-up group). We assessed the bleeding rates, bleeding-associated factors, and early-bleeding-associated factors. The treatment group’s bleeding rate was 10% (5/49). The follow-up group’s bleeding rate was 78% (21/24). The subsequent bleeding rate was low in the treatment group (p < 0.001). The median period of sustained absence of bleeding was longer in the treatment group than in the follow-up group (1156 [274–1582] days vs. 105 [1–336] days; p < 0.001). In the follow-up group, a significant number of bleedings had varices that included a hematocystic spot (HCS) as RC or combined with RC (p = 0.017). Early bleeding occurred often in varices that included HCS or combined with RC (p = 0.024). Red wale marking (RWM) only was not a factor of early bleeding (p = 0.012). In conclusion, RC-positive varices should be treated even as F1 varices. Patients with RWM only show the possibility of not accepting early treatment intervention. A fast response is crucially important in HCS cases because of its associated bleeding and early bleeding.

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBD) of unknown etiology, characterized by repeated relapse and remission. The efficacy of thiopurine in IBD was first reported in the late 1960s. Thiopurines are used to alleviate the symptoms of IBD, especially UC. These drugs have a steroid-sparing potential and are widely used for the purpose of maintaining long-term remission in steroid-dependent cases. Therefore, thiopurines tend to be used long-term, but adverse events that accompany long-term use, such as lymphoproliferative disorders, must be monitored with care. In contrast, thiopurine plays a critical role in controlling the immunogenicity of biologics. Furthermore, although thiopurine is an old drug, new findings, including the prediction of serious adverse events such as severe alopecia and acute advanced leukopenia, by nudix hydrolase 15 gene polymorphism analysis, as well as the possibility of appropriate drug monitoring by detailed analysis of 6-thioguanine nucleotides have been clarified. However, the consequences of thiopurine withdrawal have not been determined and further studies, including randomized controlled trials, are necessary to answer the clinical question regarding the scenarios in which thiopurine withdrawal is possible.

Endoscopic stone removal is currently the first-line procedure for the treatment of common bile duct stones. Advances in equipment and treatment techniques have expanded the scope of application of endoscopic treatment to include stones that have previously been difficult to remove endoscopically, such as stacked stones and large stones. For the treatment of common bile duct stones in elderly patients in particular, long-term placement of a biliary stent is increasingly being selected. Although periodic stent replacement is required, some reports have stated that biliary stenting is useful in terms of treatment-associated invasiveness and the incidence of accidental complications. To date, various opinions have been presented on whether the treatment of bile duct stones should aim for complete removal of stones or adopt the biliary stenting approach. Findings in previous reports suggest that both the approach for complete stone removal and the long-term stenting approach are associated with advantages and disadvantages. In this study, we reviewed previous reports on the significance of placing a stent and implementing careful monitoring rather than stone removal in patients with bile duct stones.

A 25-year-old man was admitted to our institution for remission induction therapy to treat a 12-year condition of ulcerative colitis (UC). Previously, he was treated with drugs, such as mesalamine, immunomodulators, prednisolone (PSL), and anti-TNFα anti-body, but remission was not maintained. Therefore, we started remission induction therapy with 20 mg/day of tofacitinib (TOF) to inhibit the action of Janus kinase. On the 29th day after TOF administration, he developed a lung abscess with high fever. A chronic bulla was already present in his lung; therefore, the lung abscess was likely formed due to a combination of the bulla being present and the pharmacological effects of TOF. Our report is significant as it highlights the compounding association between TOF and PSL therapy and bulla presence with the rare adverse effect of developing an abscess.

Endoscopic ultrasonography (EUS) has been applied to the diagnosis of various digestive disorders. Although it has been widely accepted and its diagnostic value is high, the dependence of EUS diagnosis on image interpretation done by the endosonographer has persisted as an important difficulty. Consequently, high interobserver reliability (IOR) in EUS diagnosis is important to demonstrate the reliability of EUS diagnosis. We reviewed the literature on the IOR of EUS diagnosis for various diseases such as chronic pancreatitis, pancreatic solid/cystic mass, lymphadenopathy, and gastrointestinal and subepithelial lesions. The IOR of EUS diagnosis differs depending on the disease; moreover, EUS findings with high IOR and those with IOR that was not necessarily high were used as diagnostic criteria. Therefore, to further increase the value of EUS diagnosis, EUS diagnostic criteria with high diagnostic characteristics based on EUS findings with high IOR must be established.

Most cases of Dieulafoy's lesion, a rare cause of upper gastrointestinal bleeding, occur in the upper gastric corpus, usually with no edematous bulging or fold convergence around the mucosal defect. This report describes a case of Dieulafoy's lesion with subepithelial lesion (SEL)-like morphology. Endoscopic treatment by hemoclipping was difficult. Because of repeated bleeding, abdominal dynamic contrast computed tomography (CT) was conducted. Results showed a large caliber, tortuous artery branching directly from the celiac artery and feeding into the gastric wall of the gastric fundus. Rupture of this vessel in the submucosa was thought to be responsible for the SEL-like morphology. All findings indicated endoscopic treatment from the gastric mucosal side was too difficult. Therefore, we treated the lesion using interventional radiology (IR) technique of vascular embolization. If an SEL-like Dieulafoy's lesion cannot be treated by endoscopic hemostasis, then IR might be necessary to treat the vascular anomaly.

Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in "rural" regions. Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan. Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events. Conclusion: G/P therapy is effective and safe for old-aged patients.

Aims To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Materials and methods In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin group (5 mg/d; n = 33) or a control group (n = 24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed using transient elastography to measure controlled attenuation parameter (CAP) and liver stiffness, respectively. Results Baseline liver stiffness measurement (LSM) was positively correlated with several markers and scoring systems for liver fibrosis. In week 24, there was a significant decrease in CAP from 314 ± 61 to 290 ± 73 dB/m (P = 0.0424) in the dapagliflozin group, while there was no significant change in the control group. In addition, LSM tended to decrease from 9.49 ± 6.05 to 8.01 ± 5.78 kPa in the dapagliflozin group. In 14 patients from this group with LSM values ≥8.0 kPa, indicating significant liver fibrosis, LSM decreased significantly from 14.7 ± 5.7 to 11.0 ± 7.3 kPa (P = 0.0158). Furthermore, serum alanine aminotransferase and γ-glutamyltranspeptidase levels decreased in the dapagliflozin group, but not in the control group, and visceral fat mass was significantly reduced in the dapagliflozin group. Conclusions Based on these findings, the sodium-glucose co-transporter-2 inhibitor dapagliflozin improves liver steatosis in patients with type 2 diabetes and NAFLD, and attenuates liver fibrosis only in patients with significant liver fibrosis, although the possibility cannot be excluded that a reduction in body weight or visceral adipose tissue by dapagliflozin may be associated with a decrease of liver steatosis or fibrosis.

Objective：To investigate the significance of additional hepatitis B （HB） vaccination in medical students who were unresponsive to a primary vaccine series or those who had lost antibody to hepatitis B surface antigen （anti-HBs）.Methods：Subjects were followed up for 3 years after completion of a primary HB vaccine series. One additional dose was given to those who lost the anti-HBs within 3 years after the initial series, while 3 doses were given to those who had not responded to the initial vaccination. Subjects：100 medical students （59 men and 41 women；mean age on admission to university, 19.4±1.6 years） enrolled at the School of Medicine, Dokkyo Medical University in April 2012.Results：The rate of positivity for anti-HBs was 98％ soon after completion of the primary HB vaccine series and decreased without the need for additional vaccination to 79％, 61％, and 55％ at 1, 2, and 3 years after the primary series, respectively. Eighteen vaccinated subjects （18％） lost the anti-HBs 2 years after the primary series, and all of them responded to 1 additional dose. Another 18 successfully vaccinated subjects （18％） were anti-HBs negative both 1 and 2 years after the primary series；17 of them responded to 1 additional dose. As for 2 subjects （2％） who were unresponsive to the primary series, 1 became anti-HBs-positive for the first time after 3 additional doses given 2 years after the primary series.Conclusion：A number of students became or remained anti-HBs negative after the primary HB vaccination, indicating that its timing and dose of additional vaccination need to be studied further to evaluate its utility.

Highlights • We report successful surgical treatment of Heyde syndrome. • The incidence of Heyde syndrome is expected to increase in aging population. • Heyde syndrome should be considered in AS patients with gastrointestinal bleeding. • Radical surgery should be performed regardless of gastrointestinal bleeding., Introduction The combination of aortic stenosis, acquired coagulopathy, and anemia due to gastrointestinal (GI) bleeding is described as Heyde syndrome. Presentation of case We report a surgical case of a 77-year-old man who was admitted because of melena and exertional chest compression. GI endoscopy could not reveal the origin of the GI bleeding. Conservative therapy including fasting and transfusion improved the anemia. Echocardiography demonstrated severe aortic stenosis (AS) with a hypertrophied left ventricle. Hematologic examination by gel electrophoresis showed deficiency of high-molecular-weight multimers of von Willebrand factor (vWF), resulting in the diagnosis of Heyde syndrome. He electively underwent aortic valve replacement (AVR) with a bioprosthesis using standard cardiopulmonary bypass. In the perioperative period, the patient had no recurrent anemia. He was discharged without subjective symptoms on postoperative day 18. The 20-month follow-up was unremarkable, with no episode of recurrent GI bleeding. Discussion Heyde syndrome is associated with acquired von Willebrand disease type IIA and AS. The true characteristic of von Willebrand disease type IIA is hemorrhagic diathesis caused by deficiency of high-molecular-weight multimers of vWF. Under the influence of high shear stress caused by AS, vWF is stretched and easily cleaved by vWF-cleaving protease. Consequently, it causes deficiency of high-molecular-weight multimers of vWF and primary hemostasis impairment. Therefore, the most effective treatment for Heyde syndrome is correction of AS. AVR can improve not only the hemodynamic status but also coagulopathy. Conclusion The differential diagnosis of patients with recurrent GI bleeding with concurrent systolic murmur should include Heyde syndrome.

No ideal small-diameter vascular graft for widespread clinical application has yet been developed and current approaches still suffer from graft failure because of thrombosis or degeneration. Decellularized vascular grafts are a promising strategy as they preserve native vessel architecture while eliminating cell-based antigens and allow for autologous recellularization. In the present study, a functional in vivo rodent aortic transplantation model was used in order to evaluate the benefit of bioactive coating of decellularized vascular grafts with vascular endothelial growth factor (VEGF) conjugated to a temperature-sensitive aliphatic polyester hydrogel (HG). Luminal HG-VEGF coating persistence up to 4 weeks was confirmed in vivo by rhodamine-labelling. Doppler-sonography showed that the grafts were functional for up to 8 weeks in vivo. Histological and immunohistochemical analysis of the explanted grafts after 4 weeks and 8 weeks in vivo demonstrated significantly increased endothelium formation in the HG-VEGF group compared with the control group (luminal surface covered with single-layered endothelium, 4 weeks: 64.8 ± 7.6% vs. 40.4 ± 8.3%, p = 0.025) as well as enhanced media recellularization (absolute cell count, 8 weeks: 22.1 ± 13.0 vs. 3.2 ± 3.6, p = 0.0039). However, HG-VEGF coating also led to increased neo-intimal hyperplasia, resulting in a significantly increased intima-to-media ratio in the perianastomotic regions (intima-to-media ratio, 8 weeks: 1.61 ± 0.17 vs. 0.93 ± 0.09, p = 0.008; HG-VEGF vs. control). The findings indicate that HG-VEGF coating has potential for the development of engineered small-diameter artificial grafts, although further research is needed to prevent neo-intimal hyperplasia. Copyright © 2016 John Wiley & Sons, Ltd.

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p

A 26-year-old man was admitted to our institution for ulcerative colitis treatment. He used mesalamine, steroid, immunomodulators, and anti-TNFα anti-body, but it was difficult to maintain remission. We started induction therapy with tofacitinib (TOF) 10 mg twice daily. He maintained clinical remission but had chest pain 44 days after the start of TOF. Esophagogastroduodenoscopy showed multiple ulcers from middle to lower esophagus. Although rare, TOF induced esophageal ulcers were considered based on his clinical course and endoscopic findings.

We herein report a case with aneurysm rupture in the arc of Bühler (AOB) caused by median arcuate ligament syndrome (MALS). The patient experienced a sudden onset of upper abdominal pain. Contrast-enhanced abdominal computed tomography (CT) showed an iso- to hyper-enhancing area mainly ranging from the dorsal aspect of the pancreatic head to the retroperitoneum around the right kidney. Abdominal angiography revealed marked stenosis in the origin of the celiac artery caused by MALS and a 7-mm saccular aneurysm in the AOB. Thus, we diagnosed the pain as having been caused by aneurysm rupture in the AOB due to MALS. The patient’s symptoms and anemia also improved to normal range without surgery. Careful follow-up, considering possible recurrence of aneurysm at other sites in the future, is essential.

Background and study aim: Transjugular liver biopsy (TJLB) can be used in patients who are ineligible for percutaneous liver biopsy (PLB) with acute and chronic hepatic disease. This study aimed to evaluate the usefulness and safety of TJLB in patients who were not indicated for PLB. Methods: Between July 2014 and February 2019, a total of 134 patients underwent liver biopsies at our institution. Among these, PLB was performed in 110 patients and TJLB in 24 patients. A retrospective comparison of clinical results in these patients was then performed. The primary endpoints of this study were the utility and safety of TJLB in patients who were not indicated for PLB. Results: The procedural success rate was 100% in both groups. The clinical response rate and the effective tissue sampling rate were 100% in the TJLB group and 97% in the PLB group (p = 0.55). There was no difference in the number of portal fields examined retrospectively between the two groups. No serious adverse events were observed in either group. Conclusions: It is suggested that TJLB is useful because it can be safely performed in patients with poor general condition who are not indicated for PLB.

Esophageal varices are caused by the development of collateral circulation in the esophagus as a result of portal hypertension. It is important to administer appropriate preventive treatment because bleeding varices can be fatal. Esophageal varices have complex and diverse hemodynamics, and there are various variations for each case. Endoscopic ultrasound (EUS) can estimate the hemodynamics of each case. Therefore, observation by EUS in esophageal varices provides useful information, such as safe and effective treatment selection, prediction of recurrence, and appropriate follow-up after treatment. Although treatment for the esophagogastric varices can be performed without EUS imaging, understanding the local hemodynamics of the varices using EUS prior to treatment will lead to more safe and effective treatment. EUS observation is an indispensable tool for thorough variceal care.

Objective. There is no consensus regarding administration of propofol for performing endoscopic submucosal dissection (ESD) in patients with comorbidities. The aim of this study was to evaluate the safety and efficacy of propofol-induced sedation administered by nonanesthesiologists during ESD of gastric cancer in patients with comorbidities classified according to the American Society of Anesthesiologists (ASA) physical status. Methods. Five hundred and twenty-two patients who underwent ESD for gastric epithelial tumors under sedation by nonanesthesiologist-administrated propofol between April 2011 and October 2017 at Dokkyo Medical University Hospital were enrolled in this study. The patients were divided into 3 groups according to the ASA physical status classification. Hypotension, desaturation, and bradycardia were evaluated as the adverse events associated with propofol. The safety of sedation by nonanesthesiologist-administrated propofol was measured as the primary outcome. Results. The patients were classified according to the ASA physical status classification: 182 with no comorbidity (ASA 1), 273 with mild comorbidity (ASA 2), and 67 with severe comorbidity (ASA 3). The median age of the patients with ASA physical status of 2/3 was higher than the median age of those with ASA physical status of 1. There was no significant difference in tumor characteristics, total amount of propofol used, or ESD procedure time, among the 3 groups. Adverse events related to propofol in the 522 patients were as follows: hypotension (systolic blood pressure<90 mmHg) in 113 patients (21.6%), respiratory depression (SpO2<90%) in 265 patients (50.8%), and bradycardia (pulse rate<50 bpm) in 39 patients (7.47%). There was no significant difference in the incidences of adverse events among the 3 groups during induction, maintenance, or recovery. No severe adverse event was reported. ASA 3 patients had a significantly longer mean length of hospital stay (8 days for ASA 1, 9 days for ASA 2, and 9 days for ASA 3, P=0.003). However, the difference did not appear to be clinically significant. Conclusions. Sedation by nonanesthesiologist-administrated propofol during ESD is safe and effective, even for at-risk patients according to the ASA physical status classification.

Hepatocellular carcinoma (HCC) can be difficult to diagnose and treat in patients with Osler-Rendu-Weber disease due to vascular malformation and regenerative nodular hyperplasia. In addition, percutaneous liver puncture should be avoided for the diagnosis and treatment as the procedure carries a high risk of bleeding. We herein report the successful treatment of HCC in a patient with Osler-Rendu-Weber disease using radiofrequency ablation (RFA) under laparoscopy. A 71-year-old man with Osler-Rendu-Weber disease was admitted to our hospital for the treatment of HCC. He also had chronic hepatitis C virus infection. The arterioportal shunts in the liver were detected by computed tomography (CT) and angiography. A tumor 20 mm in size was detected as a defected-lesion in the hepatic segment IV during the portal phase by CT. RFA under laparoscopy was performed for the curative treatment for HCC, with sufficient ablation obtained. Although the blood gushed out from the needle tract at the end of the procedure, complete hemostasis was achieved promptly using coagulation forceps. The post-operative course was favorable. Thus, laparoscopic RFA is a useful treatment modality for HCC in patients with Osler-Rendu-Weber disease, as a hemostasis device can be used with direct visualization.

We describe the surgical management of a 58-year-old man with inflammatory abdominal aortic aneurysm (IAAA) following treatment with preoperative steroids. The patient was transferred to our institution for abdominal pain and fever. Contrast-enhanced computed tomography showed juxtarenal abdominal aortic aneurysm surrounded by dense perianeurysmal fibrous tissue. Under a diagnosis of IAAA, steroid therapy with prednisolone was initiated to control the perianeurysmal inflammation. It continued for 3 weeks with a decreasing dose schedule, with remarkable decrease in the soft tissue mass. The patient underwent elective surgery 21 days after commencing steroid therapy. During surgery, adjacent organs were adherent to the aneurysmal wall, but fibrotic change to the retroperitoneum was very limited. He recovered uneventfully, and was discharged on postoperative Day 10. Therefore, it can be concluded that preoperative steroid therapy could minimize the operative risk for IAAAs, and improve surgical outcome.