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1.
Sci Rep ; 10(1): 10377, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587357

RESUMO

Anti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD-L1 and PD-L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD-L1 was recently found to be expressed on CD14+ cells from cancer patients. We investigate PD-1 ligands expression on CD14+ cells of patients with HCC and the role of CD14+ cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14+ cells from patients with HCC expressed PD-L1 (4.5-95.5%) and PD-L2 (0.2-95.0%). According to cut-off values, we classified patients as those either with PD-L1+PD-L2+CD14+ cells or other types of CD14+ cells. The overall survival of patients with PD-L1+PD-L2+CD14+ cells was shorter than that of patients with other types of CD14+ cells (p = 0.0023). PD-L1+PD-L2+CD14+ cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8+ cells from patients with PD-L1+PD-L2+CD14+ cells were suppressed by co-cultivation with CD14+ cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8+ cells. In conclusion, some patients with HCC have PD-L1+PD-L2+CD14+ cells that suppress their antitumor response. These inhibitory functions of CD14+ cells may be associated with a poor prognosis in these patients.

2.
Gan To Kagaku Ryoho ; 47(6): 985-988, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32541180

RESUMO

A 59-year-old woman had a history of distal gastrectomy and D2 dissection in May 200X for advanced gastric cancer(GC) in the antrum area. The pathological stage was poorly differentiated, T2(SS), N2, H0, P0, CY0, M0, pStage ⅢA. After administration of S-1 for 1 year as adjuvant chemotherapy, the patient underwent surveillance with no recurrence. However, remnant GC was diagnosed in April 200X+12. Considering that there was no indication for curative resection due to severe invasion of the proper hepatic artery, gastrojejunostomy was performed for the anastomotic stenosis. Although the patient was administered 3 courses of S-1 plus oxaliplatin therapy as first-line treatment, partial response was not achieved. Therefore, chemoradiotherapy(CRT)with capecitabine was administered for local tumor control. Complete response was achieved, and the patient underwent surveillance with no recurrence 16 months after the recurrence. There were no serious acute adverse events(AEs)during CRT and late AEs after CRT. The patient was successfully treated with CRT for locally advanced remnant GC. Although there is no standard treatment for locally advanced remnant GC, this case showed the effectiveness of CRT.

3.
Endoscopy ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32542635

RESUMO

Background With endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), guidewire manipulation might be a critically limiting step for non-experts. However, the causative factors for difficulties with guidewire manipulation remain unclear. The aim of this study was to evaluate factors associated with successful guidewire manipulation. Method This retrospective cohort study included consecutive patients who underwent EUS-HGS between October 2018 and October 2019. We measured scope angle between the long and angle axes of the echoendoscope using still fluoroscopic imaging immediately after puncturing the intrahepatic bile duct. Factors associated with successful guidewire insertion were assessed by multivariable analysis using logistic regression. Result The influence of the angle between the FNA needle and echoendoscope on failed guidewire insertion was assessed using ROC curves. Area under the ROC curve was 0.86 (95% confidence interval [CI], 0.00-0.76), and an angle of 135° offered 88.0% sensitivity and 82.9% specificity for predicting successful guidewire insertion. According to multivariable analysis, only angle between the FNA needle and echoendoscope >135° was independently associated with successful guidewire insertion (odd ratio, 0.034; 95%CI, 0.008-0.144; P<0.05), although sex, puncture site, and diameter of puncture site were not significant factors. After multivariable analysis, all variables were adjusted using age 70 or <70 years, yielding the same results. Conclusion In conclusion, angle between FNA needle and echoendoscope might be associated with successful guidewire manipulation during EUS-HGS. Adjusting between FNA needle and echoendoscope to 135° before puncturing the intrahepatic bile duct might be helpful to obtain successful guidewire manipulation during EUS-HGS.

4.
Dig Dis ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32512575

RESUMO

BACKGROUND: Recently, lumen-apposing metal stents (LAMS) have been developed as novel devices for not only EUS-guided pancreatic fluid drainage, but also for EUS-guided gallbladder drainage (GBD). Although LAMS might be clinically impactful, these stents have not yet become available as EUS-GBD stents in all countries, including Japan. Instead, improved metal stents (NEO stents) have become available. The aim of this pilot study was to evaluate the feasibility and safety of EUS-GBD using the improved metal stent with an anti-stent migration system for acute cholecystitis (AC). METHOD: The gallbladder was punctured using a 19-G needle, and a 0.025-inch guidewire was inserted into the gallbladder. After fistula dilation, stent deployment was performed from the gallbladder to the duodenum. Finally, a plastic 7-Fr pigtail stent was placed to prevent stent migration. RESULT: EUS-GBD using NEO stents with the anti-stent migration system was attempted in 12 consecutive patients with AC as a complication of other conditions. EUS-GBD was successfully performed in all patients without any adverse events, and clinical success was achieved in all patients. Median procedure time was 19.0 min (range, 19-24 min). In four patients, stent removal was successfully performed after 3 months. Stent migration during follow-up (median, 189 days) was not seen in any of the patients. CONCLUSION: Although this study has several limitations such as small number of patients and short follow-up period, the results show that NEO stents might be suitable as EUS-GBD stents in selected patients. Our results should be validated by a larger prospective, randomized study.

5.
Dig Endosc ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32470171

RESUMO

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed. The risk of infection in patients should be evaluated in advance by questionnaire and body temperature. The health of staff must be checked every day. Decisions to employ endoscopy should be based on the institutional conditions and aims of endoscopy. All endoscopic staffs need to wear appropriate personal protective equipment (PPE). The endoscope and other devices should be cleaned and disinfected after procedures in accordance with relevant guidelines. Optimal management of the endoscopy unit is required. Endoscopy for infected patients or those with suspected infection demands exceptional caution. When a patient who undergoes endoscopy is later found to have COVID-19, the members of staff involved are considered exposed to the virus and must not work for at least 14 days if their PPE is considered insufficient. When PPE resources are limited, some equipment may be used continuously throughout a shift as long as it is not contaminated. Details of the aforementioned protective measures are described.

6.
Intern Med ; 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32448842

RESUMO

A 68-year-old woman presented with a 2-year history of worsening unsteady gait. Her neurological examination revealed peripheral neuropathy with lower limb sensory dominance. T2-weighted imaging revealed a disorder of the posterior cervical cord. Blood test findings revealed vitamin B12 deficiency, and gastroscopy revealed typical findings of autoimmune gastritis. She received vitamin B12 supplementation, but some peripheral neuropathy symptoms persisted due to longstanding vitamin B12 deficiency. Asymptomatic patients should undergo gastroscopy to detect autoimmune gastritis, as chronic vitamin B12 deficiency causes irreversible peripheral neuropathy.

8.
Gastrointest Endosc ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32334019

RESUMO

BACKGROUND AND AIMS: No data appear to have been reported regarding bleeding risk among patients receiving antiplatelet and anticoagulant treatment during EUS-guided biliary drainage (BD) procedures. The aim of this study was to assess whether hemorrhagic adverse events associated with EUS-BD are increased in patients on antiplatelet and anticoagulant treatment. METHODS: Patients receiving antiplatelet and/or anticoagulant treatment who underwent EUS-BD were retrospectively enrolled between May 2015 and August 2019. Patients who did not receive antiplatelet and/or anticoagulant treatment (AP/AC) and who underwent EUS-BD in the same period were also enrolled as a control group. RESULTS: A total of 195 patients who underwent EUS-BD was enrolled in this study. Among these, 154 patients were allocated to the control group, and 41 patients to AP/AC group. Overall frequency of adverse events did not differ significantly between the control group (16.2%, 25/154) and AC/AP group (17.1%, 6/41; P=0.80). The overall bleeding event rate was 3.6% (7/195) with no significant difference between the 2 groups. No thromboembolic events were observed with or without interruption of antiplatelet and/or anticoagulant agents. According to logistic regression analysis, the use of antiplatelet and/or anticoagulant agents was not a risk factor significantly associated with bleeding events (OR, 2.96; 95% CI, 0.56-14.0; P=0.18). On the other hand, a long procedure time (>20 min) was an independent risk factor associated with bleeding events. CONCLUSIONS: In conclusion, bleeding events appear infrequent among patients who undergo EUS-BD while continuing antiplatelet and/or anticoagulant agents.

9.
Dig Endosc ; 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32335946

RESUMO

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

12.
Surg Endosc ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932928

RESUMO

BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJS) is a rare complication after pancreatoduodenostomy. However, the rate of HJS may be increased with the expansion of operative indications, such as intraductal papillary mucinous neoplasm. Recently, the indications for EUS-guided biliary drainage to treat benign biliary disease have expanded. Recently, novel transluminal treatment protocol has been established in our hospital. The aim of this study was thus to evaluate the technical feasibility and safety of our treatment protocol. PATIENTS AND METHOD: Consecutive patients with complications of HJS between January and December 2018 were enrolled in this study. EUS-guided hepaticogastrostomy (HGS) is firstly performed. After 7 days to create the fistula, HGS stent is removed. HJS is transluminally evaluated by a cholangioscope, and antegrade balloon dilation is attempted. After 3 months, if HJS is still presence, antegrade stent deployment is performed using a covered metal stent. Also, after 1 month, antegrade stent removal is transluminally performed. RESULTS: Among total 29 patients, 14 patients were underwent antegrade metal stent deployment. The technical success rate of antegrade stent deployment was 92.9%. Median period of stent placement was 30.5 days (range 28-38 days), and transluminal stent removal was successfully performed in all patients. During follow-up (median 278 days; range 171-505 days), recurrence of HJS was seen in 2 patients. Severe adverse events were not seen in any patients during follow-up period. CONCLUSION: Transluminal stent deployment for HJS under EUS-guidance appears feasible and safe, although further study with a larger sample size and longer follow-up is warranted.

13.
Aliment Pharmacol Ther ; 51(5): 534-543, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31990424

RESUMO

BACKGROUND: Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. AIMS: To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. METHODS: This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints. RESULTS: Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. CONCLUSIONS: Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).

14.
Biochem Biophys Res Commun ; 521(3): 632-638, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31679690

RESUMO

O-GlcNAcylation is a dynamic and reversible post-translational modification of cytonuclear molecules that regulates cellular signaling. Elevated O-GlcNAcylation is a general property of cancer and plays a critical role in cancer progression. We previously showed that the expression of FOXM1, a critical oncogenic transcription factor widely overexpressed in solid tumors, was elevated in MKN45 cells, a human gastric cancer cell line, by the O-GlcNAcase inhibitor Thiamet G (TMG), which induces augmented O-GlcNAcylation. Here, we identified FBXL2 E3 ubiquitin ligase as a new target of O-GlcNAcylation. Consistent with the results in MKN45 cells, FOXM1 expression was increased, accompanied by its decreased ubiquitination and degradation by TMG in the other gastric cancer cell lines, including NUGC-3 cells. We found that FBXL2 ubiquitinated FOXM1, and the interaction with FBXL2 and ubiquitination of FOXM1 were reduced by TMG in NUGC-3 cells. Interestingly, FBXL2 was also ubiquitinated, which was promoted by TMG in the cells. Moreover, FOXM1 expression and cell proliferation were reduced in FBXL2-induced NUGC-3 cells, and the reductions were attenuated by TMG, indicating that FOXM1 was stabilized by O-GlcNAcylation-mediated degradation of FBXL2 to induce cancer progression. These data suggest that elevated O-GlcNAcylation contributes to cancer progression by suppressing FBXL2-mediated degradation of FOXM1.

15.
J Hepatobiliary Pancreat Sci ; 27(2): 84-89, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31628892

RESUMO

BACKGROUND: Malignant hilar biliary obstruction (MHBO) can be treated with bilateral self-expandable metal stents (SEMS) deployed using side-by-side (SBS) or stent-in-stent (SIS) techniques. Moving cell stents (MCS) are a novel type of SEMS. The present study evaluated the technical feasibility of treating MHBO using bilateral novel uncovered SEMS to insert an SIS technique without dilating the mesh of a first stent within a single session. METHOD: We retrospectively assessed patients who were complicated with obstructive jaundice due to MHBO between August and December 2018. Technical success was defined as the deployment of a bilateral MCS into two or more biliary tracts using SIS technique without a dilation device. RESULTS: The present study analyzed data from 23 consecutive patients who were complicated with MHBO. Bilateral SIS technique with MCS was deployed in 22 (95.6%) of the 23 patients without dilating the mesh of the first stent. Multiple guidewire insertion failed in one patient with Bismuth-type IV. The median procedural duration was 33.6 min. Time to recurrent biliary obstruction was 230 days. Severe adverse events were not seen in any patients. CONCLUSION: In conclusion, uncovered moving cell SEMS might facilitate bilateral stent deployment using SIS technique.

16.
Ann Surg Oncol ; 27(1): 284-292, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31535301

RESUMO

BACKGROUND: Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. PATIENTS AND METHODS: Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. RESULTS: Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18). CONCLUSIONS: Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

19.
Surg Laparosc Endosc Percutan Tech ; 30(1): 85-90, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876888

RESUMO

INTRODUCTION: Reduced port surgery (RPS) has been garnering interest as a novel minimally invasive surgery lately. AIM: The authors examined the relationship between the number of ports and surgical outcomes after laparoscopic hepatectomy (LH). MATERIALS AND METHODS: Between January 2012 and April 2019, 209 patients who underwent laparoscopic partial resection and lateral sectionectomy were retrospectively analyzed with respect to operative variables and surgical outcomes. Patients were divided into 5 groups by the number of ports used. Student's t test, the χ test, the likelihood-ratio test, Fisher exact test, or Mann-Whitney U test were used to analyze the data. RESULTS: Operative duration was significantly longer in patients with a larger number of ports than in those with a smaller number of ports. Chronological pain scores according to the visual analog scale (VAS) on postoperative days 1, 2, 4, and 7 were not associated with the number of ports and wound length in the umbilical region. The frequency of using additional analgesic agents was not significantly different between the groups. VAS scores and the number of additional analgesic agents used were smaller in patients in whom non-steroidal anti-inflammatory drugs were regularly administered postoperatively than in those in whom the drug was not regularly administered postoperatively. LH had a 3.4% complication rate (Clavien-Dindo classification >IIIA); however, this was not significantly different between the groups. CONCLUSIONS: No significant difference in postoperative pain was observed between RPS and conventional methods, although operative durations were shorter with RPS. However, RPS for LH may be associated with excellent cosmetic results compared with conventional methods.

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