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CONTEXT: Although the combined use of the Impact Thermometer (IT) with the Distress Thermometer (DT), DIT, is reported to be a validated screening tool for clinically significant psychological distress in cancer patients, its longitudinal changes in the outpatient chemotherapy setting have not been examined. OBJECTIVES: The objective was to clarify the longitudinal changes in distress evaluated by the DIT and effects of coexisting physical symptoms in an outpatient chemotherapy setting. METHODS: A total of 297 patients who underwent chemotherapy for any malignancy on an outpatient basis were included. All the participants completed a questionnaire that included the DIT and intensities of seven physical symptoms (pain, somnolence, fatigue, dyspnea, appetite loss, abdominal distention, and nausea) at the initial and follow-up visit. RESULTS: Although 109 patients had moderate or severe distress (the DT >=4 and IT >=3) at the initial visit, 46.8% of these patients improved their distress (DIT score below the cutoff of moderate distress) at their follow-up visit. Also, 85 patients had severe distress (DT >=5 and IT >=4) at the initial visit, and 43.5% of these patients improved their distress (DIT score below the cutoff of severe distress) at their follow-up visit. In a subgroup of patients who had no severe physical symptoms at the initial visit, 69.0% and 68.4% of the patients with moderate or severe distress and severe distress at the initial visit, respectively, improved their distress (DIT scores below the cutoff of moderate and severe distress) at the follow-up visit. CONCLUSION: The distress evaluated by DIT can change on sequential measurements within short time intervals. Further study is needed to determine the appropriate use of the DIT for the screening and monitoring of psychological distress in an outpatient chemotherapy setting.Copyright © 2012 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Background: Current antiretroviral therapy (ART) regimens are highly effective; therefore, to differentiate between various regimens, considering patient-reported outcomes is essential. This study aimed to assess patient satisfaction with their current ART regimens and investigate factors associated with the Human Immunodeficiency Virus Treatment Satisfaction Questionnaire: Status (HIVTSQs) score., Methods: This cross-sectional, multicenter study was conducted in Japan between April and December 2021. Patient-reported satisfaction with ART was assessed using the Japanese version of the HIVTSQs. Binary logistic regression was used to identify factors associated with a low total HIVTSQs score., Results: A total of 679 patients completed the questionnaire. The median total HIVTSQs score was 58 (interquartile range: 52.5-64). In the multivariable logistic regression analyses, a total HIVTSQs score in the lowest quartile (indicating low satisfaction) was independently associated with twice- or thrice-daily regimens compared with single-tablet, once-daily regimens (adjusted odds ratio: 2.80, 95% confidence interval: 1.29-6.06, p = 0.009) and depression (adjusted odds ratio: 2.30, 95% confidence interval: 1.32-4.01, p = 0.003)., Conclusions: Satisfaction with the current ART regimen was high. Depression and twice- or thrice-daily ART regimen were associated with low HIVTSQ. Switching to a single-tablet, once-daily regimen may improve patient satisfaction in patients receiving twice- or thrice-daily regimens., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: People living with human immunodeficiency virus (PLWH) require high rates of medication adherence to antiretroviral therapy (ART) for a successful treatment outcome. Understanding the factors associated with incomplete adherence among those receiving integrase strand transfer inhibitor-containing single-tablet regimens (INSTI-STRs) is crucial for improving treatment outcomes. This study aimed to identify the factors contributing to incomplete ART adherence among Japanese PLWH receiving INSTI-STRs., Methods: This multicenter cross-sectional study was conducted at 11 Japanese institutions as an anonymous survey. ART adherence was assessed using a self-reported questionnaire. We defined incomplete ART adherence as missing ≥ 1 dose of antiretroviral drugs (ARVs) over the past month. The factors associated with incomplete ART adherence were assessed using logistic regression analysis. Additionally, we investigated the associations between patients' satisfaction score with and need for ARVs and their adherence to ART., Results: The final analysis included data of 387 patients who were treated with INSTI-STRs. Multivariate logistic regression demonstrated significant association of younger age (adjusted odds ratio [aOR], 0.79; 95%confidence interval [CI]: 0.64-0.99 for each 10-year increment) with incomplete ART adherence. Additionally, female sex (aOR, 3.98; 95%CI: 1.36-11.60); depressive symptoms (mild depression: aOR, 1.68; 95%CI: 1.001-2.82, moderate depression: aOR, 2.98; 95%CI: 1.35-6.53, and severe depression: aOR, 8.73; 95%CI: 1.38-55.00 vs. minimal depression); were also significantly associated with incomplete ART adherence when compared with the reference categories. Concomitant medication usage was significantly associated with a lower rate of incomplete ART adherence (1-4 medications: aOR, 0.53; 95%CI: 0.31-0.89 and ≥ 5 medications: aOR, 0.30; 95%CI: 0.13-0.70 vs. no concomitant medication usage). In the incomplete ART adherence group, satisfaction scores for various aspects were significantly lower. Furthermore, a lower proportion of patients in the incomplete ART adherence group preferred the option of "taking tablets daily and visiting the hospital every 3 months," compared to those in the complete ART adherence group (p = 0.008)., Conclusions: This study demonstrated that factors associated with incomplete ART adherence include younger age, female sex, no concomitant medication, and depressive symptoms. Despite ART simplification, incomplete adherence among PLWH receiving INSTI-STRs, remains a challenge, requiring additional actions., (© 2024. The Author(s).)

Murine endogenous retrovirus with leucine tRNA primer, also known as MERVL, is expressed during zygotic genome activation in mammalian embryos. Here we show that protein arginine N-methyltransferase 6 (Prmt6) forms a chimeric transcript with MT2B2, one of the long terminal repeat sequences of murine endogenous retrovirus with leucine tRNA primer, and is translated into an elongated chimeric protein (PRMT6MT2B2) whose function differs from that of the canonical PRMT6 protein (PRMT6CAN) in mouse preimplantation embryos. Overexpression of PRMT6CAN in fibroblast cells increased asymmetric dimethylation of the third arginine residue of both histone H2A (H2AR3me2a) and histone H4 (H4R3me2a), while overexpression of PRMT6MT2B2 increased only H2AR3me2a. In addition, overexpression of PRMT6MT2B2 in one blastomere of mouse two-cell embryos promoted cell proliferation and differentiation of the blastomere into epiblast cells at the blastocyst stage, while overexpression of PRMT6CAN repressed cell proliferation. This is the first report of the translation of a chimeric protein (PRMT6MT2B2) in mouse preimplantation embryos. Our results suggest that analyzing chimeric transcripts with murine endogenous retrovirus with leucine tRNA primer will provide insight into the relationship between zygotic genome activation and subsequent intra- and extra-cellular lineage determination., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Few reports discuss the characteristics of repeated recidivism of cholesteatoma. We describe the clinical characteristics of patients with cholesteatoma who experienced at least two recidivism episodes after initial surgery for cholesteatoma requiring canal wall reconstruction., Methods: We reviewed the medical records of 11 patients who underwent surgery for cholesteatoma with canal wall reconstruction at our department between April 2008 and March 2018 and subsequently experienced two relapses that necessitated revision surgery involving tympanomastoidectomy with canal reconstruction. Patient age at the time of the first surgery ranged from 6 to 56 (mean, 25.7) years. Seven (63.6%) of the 11 patients were male. These 11 patients were classified according to the type of recidivism, and their characteristics (pathology, operation date, operation method, pattern of relapse, and position of recurrence) were investigated., Results: Four cases involved secondary residual cholesteatoma, with the mean interval between the first revision surgery and the second revision surgery being 23.8 (range, 11-39) months. Secondary residual sites included the anterior tympanic cavity, tympanic sinus, and anterior end of the reconstructed cartilage of the canal wall. The other seven cases involved secondary recurrence, with the mean interval between the first and the second revision surgery being 26.1 (range, 12-57) months. The sites of recurrence were at the edges of the reconstructed cartilage. One notable case involved the cartilage junction, leading us to hypothesize that retraction of the temporal muscle flap and the patulous Eustachian tube was the underlying cause., Conclusion: For residual cholesteatoma, strict measures are necessary to maintain the operation under clear view, and more careful follow-up is necessary in patients who have had previous surgery at another hospital. For recurrent cholesteatoma, it was recognized that Eustachian tube function must be ascertained in advance, and careful observation of the reconstructed cartilage edge is necessary., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Long-term care issues, specifically metabolic bone disorders, are a concern for people living with human immunodeficiency virus (PLWH) who undergo life-long antiretroviral therapy (ART). Previous clinical trials with denosumab, an anti-RANKL antibody inhibitor, have revealed its effectiveness in increasing bone mineral density (BMD) in patients with osteoporosis. However, there are limited data on adherence and effectiveness of denosumab treatment for osteoporosis in PLWH. Hence, this study aimed to investigate the adherence and effectiveness of denosumab treatment for osteoporosis in Japanese PLWH., Methods: This study is a retrospective exploratory analysis of 29 Japanese PLWH who initiated denosumab treatment for osteoporosis, between 2013 and 2021. The study included patients who received at least one dose of denosumab every 6 months. Adherence and persistence were defined as receiving two consecutive injections of denosumab 6 months ± 4 weeks apart and 6 months + 8 weeks apart, respectively. The primary outcome measure of the study was the adherence of denosumab treatment for 24 months. The secondary outcome measures included treatment persistence and BMD. The period after January 2020 was defined as the coronavirus disease 2019 (COVID-19) pandemic period, and its impact on adherence was investigated., Results: The treatment adherence rates at 12 and 24 months were 89.7% and 60.7%, respectively. By contrast, the treatment persistence at 12 and 24 months was 100% and 85.7%, respectively. More patients in the group who initiated denosumab treatment after the COVID-19 pandemic reached non-adherence than in the group who initiated denosumab treatment before the pandemic. BMD at the lumbar spine and femoral neck significantly increased compared to that at baseline, with median percentage changes of 8.7% (p < 0.001) and 3.5% (p = 0.001), respectively., Conclusions: The results showed that patients in the study had a high rate of non-adherence but a lower rate of non-persistence. Additionally, PLWH on ongoing ART experienced increased BMD with denosumab treatment. This study provides an opportunity to improve future strategies for denosumab treatment in the Japanese PLWH., (© 2023. The Author(s).)

Background: Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs., Methods: People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs., Results: Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to "co-payment" and lowest with "daily oral therapy". Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030-4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010-3.030, p = 0.044)., Conclusions: Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Alectinib, crizotinib, and ceritinib, are anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) that exhibit high protein binding, and their metabolism is associated with the cytochrome P450 (CYP) isoenzymes 2C9 or 3A4. The plasma protein binding rate of warfarin, which is used to prevent and treat venous thromboembolism, is also high. Warfarin is a racemate of S-warfarin and R-warfarin, which are metabolized by CYP2C9 and CYP3A4, respectively. Reports on the drug interactions between each of the above-mentioned ALK-TKIs and warfarin with concurrent use of bucolome are currently lacking., Case Presentation: We report a case of a patient receiving warfarin and bucolome, whose international normalized ratio (INR) increased after sequential treatment with alectinib, crizotinib, and ceritinib. The patient was a 61-year-old man with a history of aortic valve regurgitation, who was receiving warfarin treatment following aortic valve replacement. Bucolome, which can enhance the effect of warfarin, was also used simultaneously. The patient was diagnosed with primary lung adenocarcinoma, and ALK rearrangement was detected during second-line chemotherapy. After progression of the disease with chemotherapy, sequential treatment with alectinib, crizotinib, and ceritinib was initiated. Pretreatment INR values were in the therapeutic range (target INR of 2-3) but increased to supratherapeutic levels each time after initiation of alectinib, crizotinib, or ceritinib treatment. Adjustment of warfarin dose or discontinuation of bucolome were necessary to maintain the therapeutic INR range. There were no serious bleeding events or substantial changes in dietary intake. Displacement of plasma protein binding or competitive inhibition of metabolism by alectinib, crizotinib, and ceritinib could increase the plasma concentration of the unbound form of warfarin, resulting in high INR values. In addition, alectinib, crizotinib, and ceritinib might cause displacement of bucolome from plasma proteins, followed by displacement of warfarin or inhibition of warfarin metabolism caused by the unbound form of bucolome., Conclusions: Close monitoring of INR and adjustment of warfarin dosage are needed during treatment with alectinib, crizotinib, or ceritinib in patients who receive warfarin with concurrent use of bucolome., (© 2023. The Author(s).)

The circadian clock allows plants to anticipate and adapt to periodic environmental changes. Organ- and tissue-specific properties of the circadian clock and shoot-to-root circadian signaling have been reported. While this long-distance signaling is thought to coordinate physiological functions across tissues, little is known about the feedback regulation of the root clock on the shoot clock in the hierarchical circadian network. Here, we show that the plant circadian clock conveys circadian information between shoots and roots through sucrose and K+. We also demonstrate that K+ transport from roots suppresses the variance of period length in shoots and then improves the accuracy of the shoot circadian clock. Sucrose measurements and qPCR showed that root sucrose accumulation was regulated by the circadian clock. Furthermore, root circadian clock genes, including PSEUDO-RESPONSE REGULATOR7 (PRR7), were regulated by sucrose, suggesting the involvement of sucrose from the shoot in the regulation of root clock gene expression. Therefore, we performed time-series measurements of xylem sap and micrografting experiments using prr7 mutants and showed that root PRR7 regulates K+ transport and suppresses variance of period length in the shoot. Our modeling analysis supports the idea that root-to-shoot signaling contributes to the precision of the shoot circadian clock. We performed micrografting experiments that illustrated how root PRR7 plays key roles in maintaining the accuracy of shoot circadian rhythms. We thus present a novel directional signaling pathway for circadian information from roots to shoots and propose that plants modulate physiological events in a timely manner through various timekeeping mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

Background: Adolescent pregnancy is a serious reproductive health problem in Tanzania. However, the risk factors for multidimensional attitudes and behaviors of reproductive health toward pregnancy in Tanzanian adolescents remain unexplored., Methods: We collected baseline characteristics and information on attitudes and behaviors of reproductive health from 4161 Tanzanian adolescents in all 54 primary and secondary schools in the Korogwe district. We applied mixed effect multiple regression analyses stratified by sex to find the factors related to reproductive health attitudes and behaviors toward pregnancy., Results: In female students, regarding the attitudes of reproductive health, higher age, hope for marriage in the future, a talk with a parent about sex or pregnancy, and a higher hope score were significantly associated with a lower score. For the behaviors of reproductive health, higher age, a talk with a parent about sex or pregnancy, time to talk with a parent about daily life, and a higher hope score were significantly associated with a lower score. In male students, regarding the attitudes of reproductive health, a higher hope score was significantly associated with a lower score. For the behaviors of reproductive health, higher age, time to talk with a parent about daily life, and a higher hope score was significantly associated with a lower score., Conclusions: The heterogeneous factor-outcomes association between female and male students suggested that sex-specialized interventions may be required to change their risky attitudes or behaviors of reproductive health. Although we cannot conclude as points of intervention, our study suggested that it may be practical to improve parent-adolescents communication about sex or reproductive health and change adolescents' views of pregnancy or marriage for gaining financial or social status., (© 2023. The Author(s).)

Background: Supporting people living with HIV using anti-retroviral therapy (ART) is important due to the requirement for strict medication adherence. To date, no data from longitudinal studies evaluating adherence by treatment-naïve people living with HIV are currently available. We investigated the adherence of treatment-naïve people living with HIV over time and examined the relationships among decisional conflicts, adherence, and health-related quality of life (HRQL)., Methods: The survey items included adherence (visual analogue scale [VAS]), decisional conflict (decisional conflict scale [DCS]), and HRQL (Medical Outcomes Study HIV Health Survey [MOS-HIV]). The DCS and MOS-HIV scores and the VAS and MOS scores were collected electronically at the ART initiation time point and at 4-, 24-, and 48-week post-treatment time points., Results: A total of 215 participants were enrolled. The mean DCS score was 27.3 (SD, 0.9); 23.3% of participants were in the high-score and 36.7% in the low-score groups. The mean adherence rates at 4, 24, and 48 weeks were 99.2% (standard error [SE], 0.2), 98.4% (SE, 0.4), and 96.0% (SE, 1.2), respectively. The least-square means of the MOS-HIV for the DCS (high vs. low scores) were 64.4 vs. 69.2 for general health perceptions and 57.7 vs. 64.0 for HRQL, respectively., Conclusion: Adherence among treatment-naïve people living with HIV was maintained at a higher level, and HRQL tended to improve with ART. People with high levels of decisional conflict tended to have lower HRQL scores. Support for people living with HIV during ART initiation may be related to HRQL., (© 2023. The Author(s).)

Background: Potential drug-drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus (HIV; PLWH). Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs)., Methods: This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface., Results: Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, P <  0.001). Furthermore, the proportion of patients on polypharmacy was significantly higher in those with PDDIs than in those without PDDIs (81.0% vs. 26.7%, P <  0.001)., Conclusions: The incidence of PDDIs is relatively high in Japanese PLWH, even in the era of treatment using integrase strand transfer inhibitors. Therefore, it is important for patients and health care providers to be constantly aware of PDDIs associated with ARV treatment., (© 2021. The Author(s).)

Introduction: The antiviral drug favipiravir has been shown to have in vitro antiviral activity against severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2). In this study, we investigated the clinical benefits and initiation of favipiravir treatment in patients with non-severe coronavirus-disease-2019 (COVID-19)., Methods: This study was a single-center retrospective cohort study. Receiver operating characteristic curves were drawn to calculate the area under the curve, and the optimal cut-off values for the time to initiate favipiravir treatment were calculated to predict defervescence within seven days. Univariate and multivariate Cox regression analyses were performed to identify potential influencing factors of defervescence. This was defined as a body temperature of less than 37 °C for at least 2 days., Results: Data from 41 patients were used for the efficacy assessment. The days from the onset of fever to defervescence showed a positive correlation with the duration from the onset of fever to initiation of favipiravir treatment (r = 0.548, P < 0.001). The optimal cut-off value was the administration of favipiravir on day 4. Patients were assigned to two groups based on the optimal cut-off value from onset to initiation of favipiravir treatment: early treatment group (within 4-days) and late treatment group (more than 4-days). In the multivariate analysis, when adjusted for age, sex, and days from onset to initiation of favipiravir treatment, the significant factors were male sex and days of initiation of the favipiravir treatment., Conclusions: We recommend that if favipiravir is to be used for treatment, it should be initiated as early as possible., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a form of necrotizing vasculitis with few or no immune deposits. It primarily affects small and medium blood vessels. AAV is classified into three categories, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangitis (EGPA), and two major ANCAs, proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA are involved in their pathogenesis. Intractable otitis media frequently occurs in patients with GPA, MPA or EGPA, although all patients show similar clinical features, regardless of the type of AAV. Furthermore, approximately 15% patients with otitis media caused by AAV do not show ANCA positivity, histopathological evidence, or any other AAV-related lesions at the initial visit; therefore, these patients do not fulfill the ordinary diagnostic criteria for systemic AAV. Thus, we first proposed that this condition could be categorized as "otitis media with AAV (OMAAV)". Subsequently, the Japanese Otological Society (JOS) conducted a nationwide survey between December 2013 and February 2014 and identified 297 patients with OMAAV. The survey revealed that OMAAV is a disease that initially occurs in the middle ear and subsequently spreads to other organs such as the lungs and kidneys, with eventual involvement of all body organs. Severe sequelae such as facial palsy, hypertrophic pachymeningitis, complete deafness, and subarachnoid hemorrhage resulting in death can also occur. In this review, we introduce the clinical features, diagnostic criteria, and treatment strategies recommended by JOS for early diagnosis and treatment of OMAAV., Competing Interests: Declaration of Competing Interest All authors require neither any financial support nor other benefits from commercial sources for the work, nor any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo , whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophage-like J774.1 cells and found that a monocatechol derivative SC1, (7α,7'α,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-β (IFN-β) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the β-glucuronidase inhibitor and enhanced by the catechol- O -methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-β/iNOS signaling through macrophage-mediated deconjugation.

Background: Endoscopic surgery is developing in various clinical specialties. During ear endoscopic surgery, a surgeon has to hold an endoscope with one hand and operate the surgical instruments with another hand. Therefore, the stability of the surgeon's hand affects the field of surgical view and quality of the surgery considerably. There are few techniques which are used during surgery to stabilize the endoscope. However, no study has evaluated the efficacy of such techniques in detail. This study examined the three dimensional movement of an endoscope to compare and evaluate the effect of various stabilization techniques to reduce the hand tremor while using the endoscope., Methods: A non-randomized controlled trial involving 15 medical students was conducted in Tottori University, Japan. Subjects held an endoscope with their non-dominant hand and manipulated it using three different stabilization techniques i.e. with resting the elbow on the table, resting the endoscope on the ear canal, both with the elbow on the table and endoscope on the ear canal. For the control, subjects were made to use the endoscope without any stabilization technique. The endoscopic movement was measured with and without using the stabilization techniques., Results: The results obtained in this study indicated that manipulating the endoscope with resting the elbow on the table restrains both vertical (Y-axis) and optical axis (Z-axis) direction of tremor, and manipulating the endoscope by resting it on the ear canal restrains both vertical (Y-axis) and horizontal axis (X-axis) direction while the combined use of both the techniques reduces the endoscope movement in all the three X, Y and Z axes., Conclusion: In conclusion, concomitant use of both techniques appears to be clinically beneficial in endoscopic ear surgery.

Background/aim: The aim of this study was to reveal risk factors for lung injury following irinotecan administration for the treatment of neoplasms., Patients and Methods: This study included 204 patients who received irinotecan from October 2005 to November 2014 and had evaluable chest CT images before initiation of irinotecan., Results: Six (2.9%) patients developed lung injury and, of these, 2 had preexisting interstitial lung disease (pre-ILD). The frequency of lung injury in patients with pre-ILD was 11% (2 of 19) while that in patients without pre-ILD was 2.2%. Risk factor analysis for the lung injury showed pre-ILD was the most predictable factor [odds ratio (OR) 5.00, p=0.07]. Combination with other agents, origin of neoplasms (lung or not), initial dose or minimum interval were not observed to be related to risk., Conclusion: The risk of lung injury with irinotecan was high when pre-ILD was present and the risk was comparable with previously reported other agents., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: In order to help a surgeon make the best decision, a more objective method of measuring ossicular motion is required., Methods: A laser Doppler vibrometer was mounted on a surgical microscope. To measure ossicular chain vibrations, eight patients with cochlear implants were investigated. To assess the motions of the ossicular chain, velocities at five points were measured with tonal stimuli of 1 and 3 kHz, which yielded reproducible results. The sequential amplitude change at each point was calculated with phase shifting from the tonal stimulus. Motion of the ossicular chain was visualized from the averaged results using the graphics application., Results: The head of the malleus and the body of the incus showed synchronized movement as one unit. In contrast, the stapes (incudostapedial joint and posterior crus) moved synchronously in opposite phase to the malleus and incus. The amplitudes at 1 kHz were almost twice those at 3 kHz., Conclusions: Our results show that the malleus and incus unit and the stapes move with a phase difference.

Objective: To investigate the usefulness of magnetic resonance imaging (MRI) including three-dimensional (3D) sequences in the differentiation between Bell's palsy (BP) and Ramsay Hunt syndrome (RHS)., Study Design: A prospective study., Setting: Tertiary care center., Patients: Twenty patients: 15 patients with BP and five patients with RHS., Intervention: Diagnostic., Main Outcome Measure: Clinical diagnosis (BP or RHS)., Results: The presence of hyperintensity on 3D-fluid-attenuated inversion recovery sequence (3D-FLAIR) and enhancement on gadolinium-enhanced (CE)-3D-FLAIR and CE-3D-T1-weighted image (3D-T1WI) along the internal auditory canal (IAC) wall were significantly associated with RHS (p < 0.05). Hyperintensity in the inner ear was observed on pre- and postcontrast 3D-FLAIR, and enhancement of the cranial nerve (CN)-VIII was observed only on CE-3D-FLAIR. The presence of these findings also showed significant relationships with RHS (p < 0.05). Moreover, thickening of the CN-VII in the fundus of the IAC in 3D-constructive interference on steady state sequence (3D-CISS) also showed a significant association with RHS (p < 0.05). In contrast, the presence of hyperintensity of the CN-VII in the fundus of the IAC on 3D-FLAIR did not demonstrate a significant relationship (p = 0.95), and enhancement in this region was observed in all cases on CE-3D-FLAIR and gadolinium-enhanced-three-dimensional-T1-weighted gradient echo sequence (CE-3D-T1WI)., Conclusions: 3D MRI sequences are useful for differentiating RHS from BP. In particular, the enhancement in the CN-VIII and/or along the IAC wall are valuable findings, and CE-3D-FLAIR is the most useful sequence to evaluate these findings. Thickening of the CN-VII on 3D-CISS is also an important finding.

Monitoring resistance allele frequency at the early stage of resistance development is important for the successful acaricide resistance management. Etoxazole is a mite growth inhibitor to which resistance is conferred by an amino acid substitution in the chitin synthase 1 (CHS1; I1017F) in T. urticae. If the susceptible allele can be specifically digested by restriction endonuclease, the ΔΔCt method using real-time PCR for genomic DNA (RED-ΔΔCt method) may be available for monitoring the resistance allele frequency. We tested whether the etoxazole resistance allele frequency in a pooled sample was accurately measured by the RED-ΔΔCt method and validated whether the resistance variant frequency was correlated with etoxazole resistance phenotype in a bioassay. Finally, we performed a pilot test using field populations. Strong linearity of the measures by the RED-ΔΔCt method with practical resistance allele frequencies; resistance allele frequency in the range between 0.5% to at least 0.75% was strictly represented. The strong linear relationship between hatchability of haploid male eggs after the etoxazole treatments (phenotype) and resistance allele frequencies in their mothers provided direct evidence that I1017F is a primary resistance factor to etoxazole in the strains used for experiments. The pilot test revealed a significant correlation between egg hatchability (including both diploid female eggs and haploid male eggs) and estimators in field populations. Consequently, we concluded that the RED-ΔΔCt method is a powerful tool for monitoring a resistance allele in a pooled sample., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV)., Methods: This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text., Results: Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p < 0.05), both ANCAs-negative phenotype (p < 0.001), and headache (p < 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002)., Conclusion: Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

Background: Plasma tenofovir (TFV) trough concentrations may be relevant for tenofovir disoproxil fumarate (TDF)-induced renal dysfunction. The purpose of this study was to determine the association between plasma TFV trough concentrations and TDF-induced renal dysfunction in Japanese patients with human immunodeficiency virus (HIV) infection., Methods: A 48-week, retrospective cohort study was performed with Japanese patients with HIV infection who started a TDF-containing combination antiretroviral therapy regimen. Plasma TFV trough concentrations were obtained at steady state. The following variables were included in the analysis: sex, age, body weight, body mass index (BMI), serum creatinine, CD4+ cell count, HIV-RNA, concomitant medications, comorbidities, plasma TFV trough concentrations, and estimated glomerular filtration rate (eGFR). For comparisons of variables, we used Mann-Whitney U tests or Fisher's exact tests. Then, variables associated with renal dysfunction in the univariate analysis were entered into correlation analysis., Results: The analysis included 11 patients. The rate of decrease in eGFR was significantly correlated with body weight (Spearman correlation = -0.645, p = 0.041), BMI (Spearman correlation = -0.682, p = 0.031), and plasma TFV trough concentrations (Spearman correlation = 0.709, p = 0.025)., Conclusions: Despite the small sample size, our findings suggest that higher plasma TFV trough concentrations may cause TDF-induced renal dysfunction. To prevent TDF-induced renal dysfunction, we propose that individual monitoring of plasma TFV trough concentrations should be performed in Japanese patients with HIV infection.

It is difficult to directly observe glottal airflow velocity just above the glottis due to sensor size requirements and limited accessibility. We developed a miniature hot-wire probe and flexible fiberscopic high-speed imaging system for human examinations. Simultaneous direct measurement of glottal airflow velocity, subglottal pressure, and vocal fold vibration was achieved in a patient who was treated with a T-tube for tracheal stenosis. Airflow velocity changes at the anterior midline of the vocal folds were synchronized with subglottal pressure changes during each phonation cycle. The velocity at the anterior midline of the vocal folds showed a rhythmic pattern of sharp, high peaks. The result of fast Fourier transform analysis indicated that glottal velocity at the anterior midline of the vocal folds had abundant high-frequency components that were not affected by resonance of the vocal tract. Airflow velocity was variable and diminished except at the anterior midline of the vocal folds.

Conclusion: Surgery remains the preferred option for large vestibular schwannoma (VS). The presence of unpredictable intraoperative difficulties may convince the operator to suspend the surgery to avoid risks to patient life. Additional surgeries may be mandatory and are better performed using a transcochlear approach. High rates of complications, poor facial nerve results, and a percentage of incomplete removals should be expected in such unfavorable cases., Objectives: To review the results for nine cases of huge VS treated by staged resection., Method: A retrospective case review was performed for all nine patients who underwent staged resection of VS at the Gruppo Otologico between 1984-2012. The decision to perform staged surgery was always made intra-operatively after encountering unpredicted difficulties., Results: The nine patients represented 0.3% of all patients who underwent VS surgery during the same period. Mean tumor size was 4.7 cm (range = 3.0-6.6 cm). Two cases required three surgeries, resulting in a total of 20 operations. In addition, two cases required pre-operative ventriculoperitoneal shunt and one required temporary tracheotomy. After the final stage of surgery, complete removal had been achieved in six of the nine patients. The facial nerve was never preserved anatomically.

Background/aims: Although previous reports have shown similar recurrence rates and patterns between laparoscopic and open surgery for colorectal cancer, precise data regarding recurrent cases are lacking., Methodology: From January 2007 to December 2011, 137 Patients with colorectal cancer underwent laparoscopic surgery at our hospital. Of the 137 patients, 7 patients with recurrence were analyzed for oncological factors. Their outcomes were compared with those of 13 patients with recurrence of 160 patients who underwent open surgery for colorectal cancer between January 2005 and December 2006., Results: In the laparoscopic group, 1 of 37 patients (2.7%) with pathological Stage II (pStage) and 6 of 37 (16.2%) with pStage III experienced recurrence; in the open surgery group, 4 of 56 patients (7.1%) with pStage II and 9 of 63 patients (14.3%) with pStage III experienced recurrence. Although majority of recurrent patterns was distant metastasis, peritoneal metastasis was observed in 2 patients with pT3 tumors in the laparoscopic group. In contrast, all 3 patients with peritoneal recurrence in the open surgery group had pT4 tumors. In the laparoscopic group, 2 patients with peritoneal metastasis were pT3N1M0, and 1 of them revealed peritoneal carcinomatosis 6 months after surgery and developed chylous ascites as a postoperative complication., Conclusions: Although the recurrence rates and sites were similar between the laparoscopic and open surgery groups, peritoneal recurrence developed only in patients with pT3 tumors in the laparoscopic group. Exfoliation of tumor cells from divided lymphatic vessels might lead to development of peritoneal recurrence after laparoscopic surgery.

Background: Numerous studies have reported sound-induced motion of the tympanic membrane (TM). To demonstrate sequential motion characteristics of the entire TM by noncontact laser Doppler vibrometry (LDV), we have investigated multipoint TM measurement., Materials and Methods: A laser Doppler vibrometer was mounted on a surgical microscope. The velocity was measured at 33 points on the TM using noncontact LDV without any reflectors. Measurements were performed with tonal stimuli of 1, 3, and 6 kHz. Amplitudes were calculated from these measurements, and time-dependent changes in TM motion were described using a graphics application., Results: TM motions were detected more clearly and stably at 1 and 3 kHz than at other frequencies. This is because the external auditory canal acted as a resonant tube near 3 kHz. TM motion displayed 1 peak at 1 kHz and 2 peaks at 3 kHz. Large amplitudes were detected in the posterosuperior quadrant (PSQ) at 1 kHz and in the PSQ and anteroinferior quadrant (AIQ) at 3 kHz. The entire TM showed synchronized movement centered on the PSQ at 1 kHz, with phase-shifting between PSQ and AIQ movement at 3 kHz. Amplitude was smaller at the umbo than at other parts. In contrast, amplitudes at high frequencies were too small and complicated to detect any obvious peaks., Conclusion: Sequential multipoint motion of the tympanic membrane showed that vibration characteristics of the TM differ according to the part and frequency.

Introduction: Until now, no data have been available on the incidence of chylous ascites after laparoscopic colorectal surgery., Methods: From January 2007 to December 2011, 137 patients with colorectal cancer underwent laparoscopic surgery at our institution. The clinical data of the patients with postoperative chylous ascites were compared with those of the patients without chylous ascites., Results: Chylous ascites developed in 9 of the 137 patients (6.5%). Blood loss, operative time, tumor location, and extent of lymph node dissection were not associated with postoperative chylous ascites. Mean postoperative hospital stay for patients with chylous ascites was significantly longer than that for patients without any complications (14 days vs 10 days; P < 0.001). Recurrence was observed in two of the nine patients with chylous ascites; it developed locally and in the liver in one patient, and peritoneal dissemination was seen in the other. The recurrence rate in the chylous ascites group (22.2%) was significantly higher than that in the non-chylous ascites group (3.9%; P = 0.016). The 3-year disease-free survival in the chylous ascites group (76.2%) was significantly lower than that in the non-chylous ascites group (93.4%; P = 0.020); however, the 3-year overall survival rates did not differ between the groups (87.5% vs 94.4%, respectively; P = 0.332)., Conclusion: Chylous ascites are not a rare complication of laparoscopic colorectal surgery. It was managed conservatively in all cases but was associated with longer hospital stays. We recommend careful tissue dissection at a suitable plane and meticulous clipping during lymphadenectomy to prevent chyle leakage when lymphatic invasion is suspected., (© 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

Objectives: The effect of adjuvant radiation therapy (RT) in extrahepatic bile duct (EHBD) cancer patients with microscopic-positive resection margins (R1 resection) is still controversial., Methods: Between January 2000 and March 2010, 52 patients with EHBD cancer underwent surgery at our institution, of whom 36 were subjected to a retrospective analysis. Eleven patients received adjuvant RT after resection [surgery (S)+RT group], which included 9 patients with R1 resection and 2 with para-aortic lymph node metastasis. Their oncological outcomes were analyzed and compared with those of the 25 patients with R0 resection who did not receive adjuvant RT (S group)., Results: Patients in the S+RT group had significantly more advanced disease than those in the S group. However, there was no significant difference in disease-free survival or overall survival between the 2 groups. Median survival times for the S+RT and the S groups were 44 and 47 months, respectively, whereas the 5-year survival rates were 38.9% and 46%, respectively (P=0.707). Locoregional recurrence was less frequent in the S+RT group as compared with the S group, but the incidence of distant metastasis was unaffected by the adjuvant RT., Conclusions: Our results support the beneficial effect of adjuvant RT in EHBD cancer patients with R1 resection. This effect seems to result from an improved control of the locoregional tumor by adjuvant RT.

Introduction: The feasibility, safety and oncological outcomes of laparoscopic surgery for transverse and descending colon cancers in a community hospital setting were evaluated., Methods: Twenty-six patients with transverse or descending colon cancers who underwent laparoscopic surgery at our hospital were included in this retrospective analysis (group A). Their outcomes were compared with those of 71 patients who underwent laparoscopic surgery for colon cancer at other tumor sites (group B)., Results: There were no significant differences between the two groups in terms of operative time, estimated blood loss, postoperative hospital stay and morbidity rate. Extended lymphadenectomy was performed more frequently and the number of harvested lymph nodes was significantly higher in group B than in group A. However, no recurrence developed in group A, while recurrence occurred in four patients from group B. The 3-year disease-free survival rates were 100% for group A and 93.5% for group B. The 3-year overall survival rates were 100% for group A and 91.6% for group B., Conclusions: Laparoscopic surgery for transverse and descending colon cancers can be performed safely with oncological validity in a community hospital setting, provided there is careful selection of the patients and adequate lymphadenectomy considering the clinical stage of their disease., (© 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

We report a case in which the atazanavir (ATV) concentration in the plasma decreased after unilateral nephrectomy in a patient receiving tenofovir (TDF). The patient was a 39-year-old man diagnosed with human immunodeficiency virus type 1 infection and was being treated with TDF/emtricitabine, ATV, and ritonavir. Before nephrectomy, ATV and TDF plasma trough concentrations were 810 and 65 ng/ml, respectively. At this time, estimated glomerular filtration rate (eGFR) was 111 ml/min/1.73 m(2). Approximately 5 months after starting antiretroviral therapy (ART), the patient underwent nephrectomy. Plasma concentrations were remeasured 18 weeks after the operation, and the TDF concentration had increased to 109 ng/ml, whereas the ATV concentration decreased to 290 ng/ml. His eGFR decreased to 50 ml/min/1.73 m(2) at the time of the second measurement. The decreased ATV plasma concentration suggested that interactions between ATV and TDF were exacerbated by an increase in TDF plasma concentration caused by renal dysfunction. This case report suggests that it is important to monitor the ATV plasma concentration to ensure that it is no less than the target trough concentration when renal function decline is observed in patients receiving ART including ATV and TDF.

We report a case of breast cancer with severe respiratory dysfunction due to multiple lung metastases, which was recovered by treatment with weekly trastuzumab administration. A 47-year-old woman with breast cancer had received a folk remedy from a general practitioner for 4 years. However, she was delivered to a hospital because of severe dyspnea, and intubation was found to be needed and performed. She was diagnosed with left breast cancer with skin and pleural wall invasion, and multiple lung metastases. Pathological examination showed invasive ductal carcinoma which was ER-postive, PgR-negative, and HER2-postive. After transfer to our hospital, treatment with trastuzumab(4mg/kg/weekly for the first course, and 2 mg/kg/weekly thereafter)was administered. Respiratory function improved gradually, and ventilator weaning was successful at 53 days after trastuzumab administration. CT examination also showed a remarkable reduction of lung and lymph node metastases and pleural effusion. She was discharged from our hospital 80 days after treatment, and her treatment with trastuzumab and capecitabine has been ongoing at an outpatient clinic.

Background: Vancomycin and linezolid therapies are associated with renal dysfunction and thrombocytopenia, respectively., Methods: We retrospectively investigated Japanese patients with renal dysfunction or thrombocytopenia possibly associated with vancomycin and linezolid therapies, including 235 patients treated with parenteral vancomycin and 178 treated with parenteral linezolid., Results: Renal dysfunction occurred more frequently in patients receiving vancomycin (24%) than in those receiving linezolid (13%; p = 0.032), whereas thrombocytopenia occurred more frequently in linezolid-treated patients (41%) than in vancomycin-treated patients (17%; p < 0.001). Controlling trough vancomycin concentrations (<20 μg/ml) protects against renal dysfunction, but thrombocytopenia may occur after >7.5 days of linezolid treatment., Conclusion: Controlling trough vancomycin concentrations to <20 μg/ml protects Japanese patients against renal dysfunction. Linezolid is an appropriate initial therapy for severe infections in patients with acute renal dysfunction, but monitoring of platelet counts is essential after initiation of therapy.

Background/aims: Similar oncological outcomes of laparoscopic and open surgery for advanced colon cancer have been reported by several large-scale studies. Whether those results are applicable to community hospitals is questionable., Methodology: From January 2007 to December 2010, 95 patients with colon cancer underwent laparoscopic surgery at Seirei Mikatahara General Hospital. Of these, 40 patients with pathological stage II/III colon cancer were subjected to this retrospective analysis (laparoscopic resection (LAP) group). Their outcomes were compared with those of 58 patients with pathological stage II/III colon cancer who underwent open surgery between January 2005 and December 2006 (open resection (OP) group)., Results: Surgical complications were significantly less frequent in the LAP group than in the OP group. Three-year disease-free survival (DFS) and overall survival (OS) for stage II colon cancer were 88.9% and 100% in the LAP group, and 90% and 86.7% in the OP group (p=0.976 and p=0.285), respectively. Three-year DFS and OS for stage III colon cancer were 85.4% and 86.9% in the LAP group, and 75.3% and 83.8% in the OP group (p=0.613 and p=0.837), respectively., Conclusions: Laparoscopic surgery for advanced colon cancer seems feasible and the oncological outcome is adequate in a community hospital setting.

Background: Previous studies have shown that the expression of Deleted in Esophageal Cancer 1 (DEC1) is significantly reduced in esophageal squamous cell carcinoma. Patients with head and neck squamous cell carcinoma (HNSCC) often develop esophageal carcinomas., Materials and Methods: We analyzed the expression of DEC1 and histone modifications in HNSCC cell lines. The motility and invasive ability of the HNSCC cell lines were also studied., Results: Of 18 cell lines, 12 (66.7%) showed down-regulation of DEC1. Chromatin immunoprecipitation assays indicated that H3 K27 trimethylation levels in the DEC1-down-regulated cell lines were greater than that in the DEC1-expressed cell lines. Migration assays showed that the DEC1-down-regulated cell lines tended to be more motile than the DEC1-expressed cell lines., Conclusion: DEC1 is down-regulated and tends to contribute to the migration ability of HNSCC cell lines. In addition, H3 K27 trimethylation potentially plays an important role in the regulation of DEC1 expression., (Copyright © 2010 S. Karger AG, Basel.)

Thioredoxin, a key molecule in redox regulation, and many redox enzymes are regulated through the antioxidant responsive element (ARE). To search for antioxidative constituents, we screened extracts from vegetables and found that the extracts of Perilla frutescens and Artemisia princeps have potent thioredoxin-inducing activities. By activity-guided purification of Perilla frutescens extracts, we identified perillaldehyde as a novel thioredoxin inducer. Fragrant unsaturated aldehydes, such as trans-cinnamaldehyde, safranal, 2,4-octadienal, citral, trans-2, cis-6-nonadienal, and trans-2-hexenal showed the ability to activate ARE. Perillaldehyde-induced activation through the ARE was suppressed by the overexpression of wild-type Keap1, whereas sulforaphane-induced activation seemed to be partially suppressed. Mutant Keap1 (R272A/K287A or C273A/C288A) did not suppress this activation. Pretreatment with perillaldehyde reduced the H(2)O(2)-induced cytotoxicity. Thus, we show that fragrant unsaturated aldehydes from edible plants are novel thioredoxin inducers and ARE activators and may be beneficial for protection against oxidative stress-induced cellular damage. These results also suggest that perillaldehyde activates the Nrf2-Keap1 system and that the lysine and arginine residues juxtaposed to the critical cysteine residues of Keap1 are required for signal sensing.

We report on a rare case of substernal thyroid carcinoma extending into the posterior mediastinum of a 48-year-old man. The tumor was resected by partial sternotomy and a small anterior thoracotomy, combined with video-assisted thoracoscopy. The pathological diagnosis was of a well differentiated papillary adenocarcinoma of the thyroid with mediastinal extension. The patient had an uneventful postoperative course and no recurrence of tumor 6 months after surgical treatment. We describe this surgical approach and discuss the advantage for cervicothoracic tumors extending into the posterior mediastinum.

To study the effects of superselective intraarterial chemotherapy with low-dose CBDCA, Pirarubicin, and concurrent radiotherapy on head and neck cancer, we compared primary cancer response and histopathological effective grades in 66 patients (more than T2) divided into radical and preoperative radiotherapy groups. The radical group (n=33) showed a 75.7% response in primary cancer, i.e. 54.5% complete remission and 21.2% partial remission. The preoperative group (n = 33) showed 39.4% complete remission when the histopathological effective grade was higher, and 57.6% partial remission when the grade was lower. Cancer response was better in the oral cavity, mesopharynx, and hypopharynx than in the parasinus. In the preoperative group, 5-year overall survival was 84.4% when the effective grade was higher, and 29.4% when the grade was lower. Survival differed significantly (P<0.01) between higher and lower grades. Additional postoperative therapy is thus essential in patients with lower grades of histopathological effectiveness.

We undertook this study to clarify the effect of immunohistochemical expression of thymidylate synthase (TS) on proliferative activity of carcinoma lesions in patients with gastrointestinal carcinoma. TS was immunohistochemically evaluated in 53 gastric carcinoma and 51 colorectal carcinoma patients using anti-TS polyclonal antibody. Proliferative activity represented by proliferating cell nuclear antigen (PCNA) labeling index (LI) was also immunohistochemically estimated using monoclonal antibody PC10. Then, the correlation between TS expression and PCNA LI was investigated. Both in gastric and colorectal carcinoma, the PCNA LIs of the high-TS group were significantly higher than those of the low-TS group. In gastric carcinoma, the PCNA LIs of the high-TS group were higher than those of the low-TS group in differentiated adenocarcinoma, in the depth of mucosal and/or submucosal layer, in cases without lymph node metastasis, and notwithstanding lymphatic or venous invasion. In colorectal carcinoma, PCNA LIs of the high-TS group were higher than those of the low-TS group in well differentiated adenocarcinoma, in the depth of serosa, in cases with lymph node metastasis, in cases with lymphatic invasion, and notwithstanding venous invasion. Immunohistochemical expression of TS was correlated with the proliferative activity represented by PCNA LI, but was not identical with PCNA LI.

Lymphagenesis in gastrointestinal tumors is not well described. To clarify its presence and regulation, we assessed the microlymphatic count (MLC) in colorectal cancer patients. Lymphatic vessels were evaluated by enzyme-histochemistry for 5'-nucleotidase (5'-NA). Since vascular endothelial growth factor (VEGF)-C is reportedly associated with lymphagenesis, the expression of VEGF-C protein was immunohistochemically assessed by the catalyzed signal amplification (CSA) method. MLC of peritumoral lesions was significantly higher than that of non-cancer and intratumoral lesions (p<0.01); it increased where VEGF-C was highly expressed (p<0.01) and increased with the depth of invasion in peritumoral lesions. These results indicate significant findings at peritumoral lesion: that lymphagenesis may be elicited by tumor spread; that VEGF-C expression is associated with lymphagenesis and is a potent factor stimulating lymphagenesis.