Effective leukemia treatment is seriously hampered by drug resistance, and the potential role of epigenetic mechanisms in cancer drug resistance has recently been investigated. With conventional anticancer drugs, including alkylating drugs, anti-metabolite drugs, topoisomerase inhibitors, and microtubule inhibitors-which have been available for half a century-drug resistance often develops because of decreased expression of target enzymes, in conjunction with increased expression of drug export pumps. Alterations of target gene expression and increased export pump function might be caused by epigenetic changes, such as alterations in methylation status, as well as by changes in histone acetylation status. In addition, newly developed anticancer drugs, including small-molecule drugs, such as kinase inhibitors, antibody drugs, and immune modulatory drugs, also resulted in development of drug resistance within 1 year, although these drugs showed significant effectiveness for patients resistant to conventional anticancer drugs. The resistant cells exhibited increased expression of bypass pathways, activation of downstream cascades, decreased expression of antigens of tumor cells, increased DNA repair activity, and increased expression of drug export pumps, which also suggests the presence of epigenetic changes. This article reviews drug resistance in cancer therapy and the possible roles of epigenetic mechanisms.

Background: Postoperative infections can be classified as surgical site infections and remote infections. Postoperative respiratory tract infections (PRTI) are a type of remote infection and may be associated with prolonged hospitalization and increased medical expenses. This study compared postoperative duration of hospitalization and medical expenses between patients with and without PRTI after gastrointestinal surgery. Methods: We retrospectively analyzed data from a multicenter study of centers affiliated with the Japan Society for Surgical Infection and used 1-to-1 matching analysis to evaluate 86 patients who underwent gastrointestinal surgery during the period from March 1, 2014 through February 29, 2016. Results: Duration of postoperative hospitalization was significantly longer for patients with PRTI (38.6 days) than for those without PRTI (16.1 days), and postoperative medical expenses were significantly higher for patients with PRTI (1388.2 USD) than for those without PRTI (629.4 USD). Conclusions: Duration of hospitalization is longer and medical expenses are higher for patients that develop surgical site infections. This study found that this was also the case for patients with PRTI after gastrointestinal surgery. However, further studies are needed in order to confirm these results.

Background: Because the indications for unicompartmental knee arthroplasty (UKA) are limited, few patients have undergone the procedure. Therefore, it is difficult to decide the acceptable range of variation in the details of UKA on the basis of the available clinical data. The objective of this study was to identify factors that affect the distribution of stress on the proximal tibia after UKA. Methods: Two-dimensional finite-element analysis of the proximal tibia was used to assess four factors: 1) two types of implants-all ultra-high-molecular-weight polyethylene (UHMWPE) and metal-backed implants, 2) postoperative alignment, 3) coverage of tibial bone, 4) level of the tibial osteotomy. Results: In cases of varus alignment, high stress values and large areas of deformation were observed on and beneath the implant. In cases of valgus alignment, stress was concentrated at the lateral portion of tibial tray. In comparison with the standard model, stress concentration was greater at the medial edge of the medial condyle in a narrow-coverage model. Stress distribution for the low-osteotomy-level model did not differ markedly differ from that for the standard model. Stress distribution was better for metal-backed implants than for UHMWPE implants. Conclusions: Proper postoperative alignment must be achieved in UKA. The osteotomy level should be set at the cancellous bone close to the joint line, and preservation of bone stock should be maximized.

Background: Some cultured neonatal rat cardiomyocytes continue spontaneous beating even in serum-free medium. The present study explored the cause and genes responsible for this phenomenon. Methods: Ingenuity Pathway Analysis (IPA) software was used to analyze fold changes in gene expression in beating neonatal rat cardiomyocytes, as compared with non-beating cardiomyocytes, which were obtained from DNA microarray data of total RNA extracts of cardiomyocytes. To confirm the involvement of the 8 genes selected by IPA prediction, cellular protein abundances were determined by Western blot. The gene expression of connective tissue growth factor (CTGF) was substantially higher in beating cardiomyocytes than in non-beating cardiomyocytes; thus, CTGF protein content released from cardiomyocytes into the culture medium was examined. Results: IPA showed that the "Apelin Cardiac Fibroblast Signaling Pathway" was significantly inhibited and that microtubule dynamics and cytoskeleton organization were significantly activated. Each fluctuation in the cellular abundances of the 8 proteins in beating cardiomyocytes, as compared with non-beating cardiomyocytes, was primarily in the same direction as that of gene expression. However, the cellular CTGF protein abundance as well as CTGF content released into the medium did not substantially differ between beating and non-beating cardiomyocytes. Conclusions: The present results suggest that the large increase in CTGF gene expression in beating cardiomyocytes is not a cause but a result of beating, which may provide a putative pathway for controlling beating. Beating is sustained by developed cardiomyofibrils and directly upregulates CTGF gene expression, which is not followed by CTGF protein synthesis.

Background: As part of the planning for a future multicenter study, this preliminary clinical trial used serum samples from patients to identify biomarkers for predicting the therapeutic effects of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis (JCP). Methods: This prospective study included patients undergoing SLIT for JCP at our hospital. All enrolled patients (N = 17) started SLIT between June and November of 2015. With informed consent from the patients, blood samples were obtained in January, March, and June of 2016, and patients completed the Japan rhino-conjunctivitis quality of life questionnaire (JRQLQ). On the basis of the JRQLQ results, the 6 patients with the best outcomes were included in the high-response group (HRG), and the 5 patients with the worst outcomes were included in the poor-response group (PRG). We then compared serum data between the two groups, to identify useful biomarkers. Results: IL-12p70 and VEGF levels tended to be higher in the HRG than in the PRG in January, March, and June (0.10 > p > 0.05). In addition, the June IL-17 level was significantly higher (p < 0.05) in the HRG than in the PRG. Conclusions: IL-12p70 and VEGF may be useful biomarkers for predicting the effects of SLIT. In addition, although IL-17 does not appear to be useful as a biomarker for evaluating treatment response at the start of SLIT, it may be useful as a biomarker after the beginning phase of SLIT.

Background: Studies of alexithymia have primarily targeted adult populations. Although some recent studies of alexithymia have focused on children and young adolescents, the literature is not sufficient for development of an assessment tool. The aim of this study was to develop, and evaluate the psychometric properties of, a new scale to measure alexithymia-like features in young adolescents. Methods: A total of 1,444 Japanese junior high school students (701 males, 743 females; age range 12-15; mean [SD] age, 13.37 [0.98] years) participated in 2 surveys conducted at their own schools. Results: First, exploratory factor analysis of the first survey data (n=981) demonstrated that this new scale had a unifactor structure, as determined by minimum average partial analysis and parallel analysis. Second, confirmatory factor analysis of the second survey data (n=463) confirmed the unifactor structure of this new scale and acceptable goodness of model fit. The new scale had modest internal consistency. Conclusions: The correlations of this new alexithymia scale with related variables were weak but significant, in accordance with our hypothesis. The scale had acceptable reliability and convergent validity and thus might be useful for measuring alexithymic tendency in young adolescents.

Diagnosis and treatment of superficial laryngopharyngeal cancers has recently received considerable attention. Here, we present a case of superficial hypopharyngeal cancer and superficial esophageal cancer treated with simultaneous endoscopic laryngopharyngeal surgery (ELPS) and endoscopic submucosal dissection (ESD). The patient was a 67-year-old man. During his follow-up for distal gastrectomy-performed earlier for stomach cancer-upper gastrointestinal endoscopy revealed three primary cancers: a superficial hypopharyngeal cancer, superficial esophageal cancer, and esophagogastric junction cancer. After total resection of the remnant stomach, combined hypopharyngeal ELPS with esophageal ESD was performed. He developed aspiration pneumonia after surgery but recovered and was discharged on the 16th day. Thus, safe and effective endoscopic therapy can be performed even for double superficial cancers of the laryngopharynx and esophagus.

In Japan, pneumococcal vaccine has been routinely administered since 2010 to prevent invasive pneumococcal diseases such as Streptococcus pneumoniae meningitis. We describe a case of pneumococcal meningitis in a 7-month-old girl who had received three doses of 13-valent pneumococcal conjugate vaccine. Brain magnetic resonance imaging showed infarcts in the right frontal region, and she was treated with antibiotics, intravenous immunoglobulin, dexamethasone, and edaravone. On day 27, an enhanced brain CT scan showed improvement of abnormal findings in the frontal region, except for slight atrophy. The S. pneumoniae serotype was 12F, which is not included in the 13-valent pneumococcal conjugate vaccine. A future vaccine is expected to use cross-reactivity to target common antigens.

Peritonitis is a common complication of peritoneal dialysis (PD) and can result in PD catheter removal, permanent hemodialysis, and, potentially, death. Prediction and prevention of PD-related peritonitis are thus extremely important. In 2016, the International Society for Peritoneal Dialysis published guidelines for patients with peritonitis undergoing PD. The guidelines cover most cases of PD-related peritonitis caused by bacteria and include clear indications for catheter removal. However, difficulties often arise when deciding the timing of catheter removal. When multiple enteric organisms are identified in a culture of dialysis effluent, peritonitis may be caused by intra-abdominal pathology, which is associated with substantial mortality. In such cases, catheter removal is considered. In this report, we describe a case in which, during antibiotic therapy for PD-related peritonitis due to Enterococcus faecalis alone, the patient developed a relapse of peritonitis caused by a newly detected Gram-negative, rod-like Pseudomonas aeruginosa. He required catheter removal because of the possibility of peritonitis recurrence. Although additional study is required, early catheter removal may be effective when a new organism is detected during antibiotic therapy for PD-related peritonitis caused by an organism not meeting the definition of refractory peritonitis.