The World Health Organization (WHO) recommends antimicrobial use density (AUD) as an indicator for evaluating the amount of antimicrobials used, an index that is now widely employed in many facilities. Defined daily doses (DDD) set by WHO are used for calculating AUD. However, discrepancies have been noted between other countries and Japan in the standard dosage of antimicrobials, which may cause a problem evaluating antimicrobial use with the DDD. Therefore, in this study, we calculated AUD (modified antimicrobial use density: mAUD) with the DDD (modified defined daily dose: mDDD) of our hospital for the carbapenem antimicrobial meropenem (MEPM), mAUD, and resistance rate of Pseudomonas aeruginosa. From 2010 through fiscal year 2016 (ending in March), AUD was 5.9±1.4, 7.0±2.9, 8.2±2.3, 6.8±2.1, 7.3±2.2, 7.0±2.1, and 8.0±3.0 and mAUD was 11.7±2.7, 12.0±4.9, 11.3±3.1, 11.0± 3.4, 11.4±3.5, 11.5±3.5, and 11.2±4.2, respectively. The corresponding resistance rate of P. aeruginosa was 35.1%, 37.9%, 10.0%, 6.0%, 22.6%, 10.6%, and 10.0%. A significant positive correlation was found between mAUD and the resistance rate of Pseudomonas aeruginosa (P < 0.01, r = 0.88). Our results confirm that the mAUD is an effective index for controlling resistance of P. aeruginosa.

PURPOSE: Gastric adenocarcinoma of the fundic gland type (chief cell predominant type) (GA-FG-CCP) was first reported as a rare adenocarcinoma found in the normal fundic mucosa. Recent studies have proposed the possibility that GA-FG-CCPs were also generated in the atrophic mucosa after Helicobacter pylori (HP) eradication therapy. However, little is known on the endoscopic findings of GA-FG-CCP generated in the atrophic mucosa due to its extreme rarity. MATERIALS AND METHODS: A total of 8 patients who underwent endoscopic submucosal resection and were diagnosed with GA-FG-CCP generated in the HP-uninfected mucosa (4 cases, HP-uninfected group) or HP-eradicated atrophic mucosa (4 cases, HP-eradicated group) were retrospectively analyzed, and their endoscopic findings, including magnifying endoscopy with narrow band imaging (M-NBI), and pathological features were compared. RESULTS: While GA-FG-CCPs in the 2 groups displayed similar macroscopic appearance, M-NBI demonstrated that characteristic microvessels (tapered microvessels like withered branches) were specifically identified in the HP-eradicated group. Pathological investigation revealed that a decreasing number of fundic glands and thinned foveolar epithelium covering tumor ducts were thought to lower the thickness of the covering layer over tumor ducts in the HP-eradicated group. Moreover, dilation of vessels just under the surface of the lesions contributed to the visualization of microvessels by M-NBI. CONCLUSIONS: The change in background mucosa due to HP infection influenced the thickness of the covering layer over the tumor ducts and M-NBI finding of GA-FG-CCP.
Adenocarcinoma ; Endoscopy ; Epithelium ; Helicobacter pylori ; Helicobacter ; Humans ; Microvessels ; Mucous Membrane ; Narrow Band Imaging ; Retrospective Studies ; Stomach Neoplasms

Background/Aims: While Helicobacter pylori (HP)-negative gastric cancer is frequently reported, little is known about the predictors for detecting HP-negative early gastric cancer (EGC). We aimed to evaluate the predictors for the detection of HP-negative EGC. Methods: We retrospectively reviewed 13,477 consecutive asymptomatic cases where upper endoscopy was performed by nine physicians from April 2017 to March 2019 and analyzed the detection rate of high-risk lesions (HRLs), including EGC, tubular adenoma, and lymphoma, according to the status of HP infection. The observation time was corrected for multiple regression analyses. Results: For all physicians, the average observation time for screening HP-eradicated and -naïve patients was shorter than that for screening HP-positive patients (p<0.05). Multiple regression analyses revealed that the observation time in the three groups was an independent predictor for detecting HRLs in HP-eradicated patients (p=0.03106, 0.01263, and 0.02485, respectively), while experience of endoscopy was an independent predictor for detecting HRLs in HP-naïve patients (p=0.02638). Conclusions While observation time during screening endoscopy was a quality indicator for detecting HRLs in HP-eradicated patients, experience of endoscopy was a quality indicator for detecting HRLs in HP-naïve patients.

In recent years, the problem of antimicrobial resistance (AMR) from inappropriate use of antimicrobial drugs has emerged, and a plan to counter AMR has been formulated. From October 2017, our hospital started interventions to guide prescribing physicians in the proper use of intravenous antibiotics for patients requiring said treatment for more than 15 days. In the present study, we investigated the status of treatment with intravenous antibiotics and considered the effects of intervention. This study targeted a total of 2627 patients, 1971 of whom were hospitalized, who started using intravenous antibiotics from June 2017 to January 2018. We assigned those who started between June and September 2017 to the pre-intervention group and those who started between October 2017 and January 2018 to the post-intervention group. The number of patients using long-term intravenous antibiotics, total number of days of treatment, antimicrobial use density (AUD), day of therapy (DOT), and rate of use by lineage of antibiotics were compared. The number of patients using long-term intravenous antibiotics decreased to 40 in the pre-intervention group and 31 in the post-intervention group. There was no significant difference in the total number of treatment days, which was 5.1 ± 5.5 days before and 4.8 ± 4 9 days after, in the intervention group. The AUD of penicillin antibiotics increased and that of aminoglycosides decreased. Furthermore, the DOT of third-generation cephems and lincomycin decreased. Penicillin had an increased lineage use ratio, while that for thirdgeneration cephems, carbapenems, and lincomycin decreased. The number of patients using long-term intravenous antibiotics as well third-generation cephem and carbapenem antibiotics, which are broad spectrum antibiotics, decreased; the overall use of penicillin, a narrow-spectrum antimicrobial, increased. This suggested that the intervention resulted in the promotion of proper use of antimicrobial drugs.

Direct-acting oral anticoagulants (DOAC) were approved for the prevention of cardiogenic embolism in non-valvular atrial fibrillation in recent years. However, the dosage of DOAC has to be reduced in patients with bleeding tendencies where the risk of hemorrhage is high, and dose reduction strategies differ depending on the type of DOAC. Therefore, we examined the dosage regimens of 4 DOACs (dabigatran, rivaroxaban, apixaban, edoxaban). Among 129 patients treated with DOACs, 85 received the standard dosage and 44 received non-standard dosage regimens. Among the non-standard dosage patients, 6 were taking a high dose (dose reduction was desirable) and 38 patients were taking a low dose (low dose is usually desirable). The low dosage group were significantly older and had a significantly lower CHADS2 score than that of the high dosage group. Hemorrhagic events occurred in 2 patients in the standard dosage group and in 3 patients in the low dosage group. Also, a thrombotic event occurred in only 1 patient in the standard dosage group. About 30% of the patients were on low dosage versus standard dosage. In practice, attending physicians tend to reduce the dose to avoid a hemorrhagic event particularly in elderly persons. However, a hemorrhagic event also occurred with low dosage in this survey. The validity and safety of dosages outside the limits of standard dosage have not been reported even though this dosage method is commonly used in clinical practice. Thus, more data should be accumulated from a large-scale cohort study to clarify this.

Drug therapy is necessary to treat metastatic and recurrent breast cancer. In Japan, two types of cyclin-dependent kinases (i.e., CDK4/6 inhibitors) are covered under the national healthinsurance system: palbociclib (since December 2017) and abemaciclib (since November 2018). Although there are many reports on the use and side effects of palbociclib in clinical practice, there are few such reports on abemaciclib. Therefore, we investigated the rate of neutropenia and associated background factors in patients taking abemaciclib. Of the 39 patients taking abemaciclib recruited for the study, 22 satisfied the inclusion criteria. Of these, 7 developed Grade 3 or higher neutropenia and had a significantly lower body weight and body mass index (BMI). Furthermore, the white blood cell and neutrophil counts before administration were significantly lower in the expression group compared with the non-expressing group. To predict the development of Grade 3 or higher neutropenia, the receiver operating characteristic (ROC) curve was used to calculate a BMI cut-off value of 23.9 (specificity 85.7%, sensitivity 73.3%, area under the ROC curve 0.80). Based on this cut-off value, BMI was divided into two groups (<23.9 and ≥23.9) and Fisher's exact test was performed. Patients with a low body mass index were more likely to develop Grade 3 or higher neutropenia as a result of increased dosage per kilogram body weight, while among patients with BMI < 25, those with BMI < 23.9 were at high risk of developing Grade 3 or higher neutropenia. Accordingly, caution is required in the treatment of such patients.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.
Antineoplastic Agents ; Asian Continental Ancestry Group ; Drug Therapy ; Education ; Endometrial Neoplasms ; Female ; Gyeonggi-do ; Humans ; Immunotherapy ; Korea ; Ovarian Neoplasms ; Radiotherapy ; Uterine Cervical Neoplasms

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*