Search

By nature, humans are " tojisha (participating subjects/player-witnesses)" who encounter an unpredictable real world. An important characteristic of the relationship between the individual brain and the world is that it creates a loop of interaction and mutual formation. However, cognitive sciences have traditionally been based on a model that treats the world as a given constant. We propose incorporating the interaction loop into this model to create "world-informed neuroscience (WIN)". Based on co-productive research with people with minority characteristics that do not match the world, we hypothesize that the tojisha and the world interact in a two-dimensional way of rule-based and story-based. By defining the cognitive process of becoming tojisha in this way, it is possible to contribute to the various issues of the real world and diversity and inclusion through the integration of the humanities and sciences. The critical role of the brain dopamine system as a basis for brain-world interaction and the importance of research on urbanicity and adolescent development as examples of the application of WIN were discussed. The promotion of these studies will require bidirectional translation between human population science and animal cognitive neuroscience. We propose that the social model of disability should be incorporated into cognitive sciences, and that disability-informed innovation is needed to identify how social factors are involved in mismatches that are difficult to visualize. To promote WIN to ultimately contribute to a diverse and inclusive society, co-production of research from the initial stage of research design should be a baseline requirement., 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.

Rationale: Gorham-Stout disease (GSD) is a rare disease that causes massive osteolysis and proliferation of abnormal lymphangiomatous tissues. Patients with GSD often experience pain associated with bone fractures and chylothorax. However, bleeding caused by abnormal lymphangiomatous tissue or hematological dysfunction rarely occurs., Patient Concerns: A 22-year-old female patient with GSD presented with severe left hip and lower limb pain. The GSD had disappeared her right pelvic bone and femur, but no abnormalities were found in the bones at the site of the pain., Diagnoses: The patient presented with a chylothorax and cerebrospinal fluid leakage. She was treated with sirolimus and an epidural blood patch, and her symptoms resolved. Computed tomography and magnetic resonance imaging revealed an epidural hematoma extending from L3 to the caudal region, and blood results revealed a consumption coagulopathy., Interventions: We presumed that the hematoma caused pain and prescribed pregabalin and morphine. The pain gradually subsided., Outcomes: An unexpected liver subcapsular hemorrhage occurred 4 months later, and the patient went into hemorrhagic shock. Transcatheter arterial embolization was promptly performed, and the patient recovered., Lessons: GSD infrequently causes bleeding related to abnormal lymphangiomatous tissues and coagulopathy, yet it can lead to serious events if it occurs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The 22q11.2 deletion syndrome (22q11DS) is characterised by a changing pattern of overlapping intellectual, physical, and mental disabilities along the course of one's life. However, the impact of overlapping disorders (multimorbidity) on educational challenges remains unclear., Method: A survey was conducted with 88 caregivers of individuals with 22q11DS. A quantitative analysis of educational challenges and support needs divided into age groups (7-12, 13-15, 16-18, and 19 years and over) and a qualitative analysis of the free-text items in the questionnaire was conducted., Results: Caregivers were more interested in comprehensive developmental support when their children were younger, and the emphasis shifted to concerns regarding environments that matched individual characteristics at older ages. Furthermore, when there are multiple disabilities or disorders, support is concentrated on the more obvious disabilities, and the lack of support for the less superficially obvious disabilities associated with multiple difficulties, including mental health problems, can be a challenge for people with 22q11DS and their families., Conclusions: This study suggests a need for increased focus on multimorbidity and associated disabilities in school education that are difficult to observe because of their mildness or borderline levels if present alone., (© 2023 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Aim: The 22q11.2 deletion syndrome (22q11DS) is associated with a high prevalence of mental health comorbidities. However, not enough attention has been paid to the elevated prevalence of high trait anxiety that begins early in life and may be enduring. We sought to identify specific medical, welfare, or educational difficulties associated with high trait anxiety in 22q11DS., Methods: A questionnaire-based survey was conducted for the parents of 22q11DS individuals ( N  = 125). First, a multiple regression analysis was conducted to confirm the hypothesis that high trait anxiety in individuals with 22q11DS would be associated with parents' psychological distress. This was based on 19 questionnaire options regarding what difficulties the parents currently face about their child's disease, characteristics, and traits. Next, we explored what challenges faced in medical, welfare, and educational services would be associated with the trait anxiety in their child., Results: The multiple regression analysis confirmed that the high trait anxiety was significantly associated with parental psychological distress ( β  = 0.265, p  = 0.018) among the 19 clinical/personal characteristics of 22q11DS. Furthermore, this characteristic was associated with various difficulties faced in the medical care, welfare, and education services, and the parent-child relationship., Conclusion: To our knowledge, this is the first study to clarify quantitatively how the characteristic of high anxiety level in 22q11DS individuals is related to the caregivers' perceived difficulties in medical, welfare, and educational services. These results suggest the necessity of designing service structures informed of the fact that high trait anxiety is an important clinical feature of the syndrome., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method., Patients and Methods: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities., Results: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%., Conclusion: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Aim: Young carers (YCs) refer to children under the age of 18 who assume responsibilities that would normally be assumed by adults, such as caring for family members in need of care. In recent years, the concept of YCs has been expanding in Japan, and the government has been rapidly implementing strategies to support them. There is a need for a survey scale for YCs that uses standardized methods that can be compared internationally., Method: The BBC/University of Nottingham Survey for estimating the prevalence of YCs and caring activities of United Kingdom adolescents was translated into Japanese, and its reliability and validity were tested with 313 adolescents. Moreover, the prevalence of YCs was estimated in a school-based survey among 5000 adolescents., Results: The Young Carers Scale Japanese version (YCS-J) was acceptably reliable and valid. The original six-factor model for caring activity in the Multidimensional Assessment of Caring Activities Checklist for Young Carers (MACA-YC18) was supported by confirmatory factor analysis. The prevalence of YCs among 5000 adolescents in the Tokyo metropolitan area was estimated to be 7.4%, comparable to that reported in Western countries and in recent surveys in Japan using nonstandardized methods. YCs exhibited significantly higher scores for prosocial behavior and emotional symptoms than non-YCs., Conclusions: The YCS-J, as an internationally comparable instrument, will be useful for understanding the actual situation of YCs in Japan, and to disseminate and implement support through cooperation among education, welfare, and healthcare sectors., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Contrast-enhanced computed tomography (CT) scan (portal phase) at the onset. Emphysema is detected in the ileal wall (b, c: Arrows) and free air is detected in the abdominal cavity (a: Arrowhead). CT scan imaging settings: (a-c) window level (WL) 60 and window width (WW) 300. (d-f) WL 0 and WW 433. By changing the imaging settings, intestinal emphysema and free air can be more easily identified., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Production of 99 Mo/ 99m Tc using an electron linear accelerator (linac) and activated carbon (AC)-based 99m Tc generator (linac-AC) is an alternative approach to the conventional fission production of 99 Mo/ 99m Tc. As a preliminary investigation of the clinical applicability of a linac-AC-derived 99m Tc radiopharmaceutical, the biodistribution of linac-AC-derived [ 99m Tc]sodium pertechnetate ([ 99m Tc]NaTcO 4 ) was measured and compared against fission-derived [ 99m Tc]NaTcO 4 at one time point., Methods: 99 Mo was produced by irradiating nonenriched MoO 3 targets with bremsstrahlung photons generated from 55.5-MeV linac electron beams. 99m Tc was then separated and purified from the 99 Mo using an AC-based 99m Tc generator. Subsequently, biodistribution of the linac-AC-derived [ 99m Tc]NaTcO 4 in healthy female Slc:ICR mice (n = 6) was measured by dissection and compared with that of fission-derived [ 99m Tc]NaTcO 4 (n = 4) at 30 min after injection., Results: The two types of [ 99m Tc]NaTcO 4 exhibited similar biodistribution in all the organs and tissues examined: the uptakes of [ 99m Tc]NaTcO 4 prepared from the linac-AC method and those prepared from the fission method were 138.9 ± 69.9%ID/g and 160.6 ± 49.2%ID/g in the thyroids, respectively, 33.4 ± 5.5%ID/g and 29.4 ± 9.1%ID/g in the salivary glands, respectively, and less than 10%ID/g in blood and all the other organs. No adverse effects were observed in the mice administered with either [ 99m Tc]NaTcO 4 ., Conclusion: The clinical applicability of linac-AC-derived [ 99m Tc]NaTcO 4 was suggested by its similar biodistribution with fission-derived [ 99m Tc]NaTcO 4 at one time point. Further biodistribution studies at multiple time points are encouraged to demonstrate the bioequivalence between linac-AC- and fission-derived [ 99m Tc]NaTcO 4 ., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Behavioral neuroscience has dealt with short-term decision making but has not defined either daily or longer-term life actions. The individual brain interacts with the society/world, but where that point of action is and how it interacts has never been an explicit scientific question. Here, we redefine value as an intrapersonal driver of medium- and long-term life actions. Value has the following three aspects. The first is value as a driving force of action, a factor that commits people to take default-mode or intrinsic actions daily and longer term. It consists of value memories based on past experiences, and a sense of values, the source of choosing actions under uncertain circumstances. It is also a multilayered structure of unconscious/automatic and conscious/self-controlled. The second is personalized value, which focuses not only on the value of human beings in general, but on the aspect that is individualized and personalized, which is the foundation of diversity in society. Third, the value is developed through the life course. It is necessary to clarify how values are personalized through the internalization of parent-child, peer, and social experiences through adolescence, a life stage almost neglected in neuroscience. This viewpoint describes the brain and the behavioral basis of adolescence in which the value and its personalization occur, and the importance of this personalized value as a point of interaction between the individual brain and the world. Then the significance of personalized values in psychiatry is discussed, and the concept of values-informed psychiatry is proposed., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objective: To examine the role of primary motor cortex in gait through exploring the dissociation of impaired voluntary leg muscle contraction and preserved rhythmic activities during gait in a patient who had a stroke., Subject and Methods: A 49-year-old man with an infarct in the primary motor cortex exhibited automatic-voluntary dissociation in the paretic leg. Functional studies were conducted using surface electromyography (EMG) and near-infrared spectroscopy (NIRS)., Results: The patient was incapable of voluntary contraction of individual leg muscles on the paretic right side but was able to walk automatically while contracting those muscles rhythmically. Surface EMG confirmed the earlier findings objectively. The preserved automatic activities helped recovery of gait capability, but NIRS showed no functional recovery in the corresponding motor cortex during treadmill gait. We considered that the loss of voluntary leg muscle contraction and the preserved gait capacity in this patient represented a form of automatic-voluntary dissociation., Conclusions: The preserved gait capability suggests that the leg representation of the primary motor cortex may not play a major functional role in gait, but other components of the nervous system, including the spinal central pattern generator, would serve important functions to maintain gait capability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Disturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects., Methods: We included 23 patients (mean age 22.3 years, 9 male) and 20 control subjects (mean age 22.4 years, 8 male). We determined dopamine metabolism in the nucleus accumbens and striatum from 18 F-fluorodopa ( 18 F-FDOPA) positron emission tomography. We measured GABA levels in the anterior cingulate cortex (ACC) and glutamate plus glutamine levels in the ACC and left thalamus with 3T proton magnetic resonance spectroscopy. We used binominal logistic regression for unimodal prediction when we modeled neurotransmitters individually and for multimodal prediction when we combined the 3 neurotransmitters. We selected the best combination based on Akaike information criterion., Results: Individual neurotransmitters failed to predict group. Three triple neurotransmitter combinations significantly predicted group after Benjamini-Hochberg correction. The best model (Akaike information criterion 48.5) carried 93.5% of the cumulative model weight. It reached a classification accuracy of 83.7% ( p  = .003) and included dopamine synthesis capacity (K i 4p ) in the nucleus accumbens ( p  = .664), GABA levels in the ACC ( p  = .019), glutamate plus glutamine levels in the thalamus ( p  = .678), and the interaction term K i 4p  × GABA ( p  = .016)., Conclusions: Our multimodal approach proved superior classification accuracy, implying that the pathophysiology of patients represents a combination of neurotransmitter disturbances rather than aberrations in a single neurotransmitter. Particularly aberrant interrelations between K i 4p in the nucleus accumbens and GABA values in the ACC appeared to contribute diagnostic information., (© 2022 The Authors.)

Background: Postsecondary student suicide is one of Japan's most severe public health problems. Gatekeeper training (GKT) programs are a generally recommended suicide prevention intervention in Japan. For suicide countermeasures, an online program tailored to students may enhance self-efficacy as a gatekeeper., Objective: This study aims to describe a research protocol to investigate the effect of a newly developed internet-delivered online peer GKT program to improve postsecondary student self-efficacy as gatekeepers for suicide countermeasures in Japan., Methods: This study is a 2-arm, parallel, randomized controlled trial with a 1:1 (intervention: waiting list) allocation. Participants (n=320) will be recruited, and those who meet the inclusion criteria will be randomly allocated to the intervention or waiting list control group. An approximately 85-minute, 6-section, internet-based gatekeeper program for postsecondary students has been developed that includes videos to help participants acquire skills as gatekeepers. The intervention group will complete the program within 10 days. The primary outcome, self-efficacy as a gatekeeper, is measured using the Gatekeeper Self-Efficacy Scale at baseline, immediately after taking the program, and 2 months after the survey after completing the program follow-up. To compare the primary outcomes, a t test, where the significance level is 5% (2-sided), will be used to test the intervention effect on an intention-to-treat basis., Results: The study was at the stage of data collection at the time of submission. We recruited participants for this study during August and September 2021, and data collection will continue until December 2021. The data analysis related to the primary outcome will start in December 2021, and we hope to publish the results in 2022 or 2023., Conclusions: This is the first study to investigate the effectiveness of an online GKT program for postsecondary students to improve self-efficacy as a gatekeeper using a randomized controlled trial design. The study will explore the potential of an online peer gatekeeper program for postsecondary students that can be disseminated online to a large number of students with minimal cost., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000045325; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051685., International Registered Report Identifier (irrid): DERR1-10.2196/34832., (©Kyosuke Nozawa, Ayaka Ishii, Hiroki Asaoka, Mai Iwanaga, Yousuke Kumakura, Yuri Oyabu, Tomohiro Shinozaki, Kotaro Imamura, Norito Kawakami, Yuki Miyamoto. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.04.2022.)

Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs sensory anesthetic effects without prolonging motor blockade. Additionally, we examined whether amiodarone provides long-lasting analgesic effects against inflammatory pain without TRPV1 channel activator co-administration. In the sciatic nerve block model, 32 adult C57BL/6J mice received either bupivacaine, amiodarone with or without capsaicin (a TRPV1 agonist), or vehicle via peri-sciatic nerve injection. Sensory and motor blockade were assessed either by pinprick and toe spread tests, respectively. In another set of 16 mice, inflammatory pain was induced in the hind paw by zymosan injection, followed by administration of either amiodarone or vehicle. Mechanical and thermal sensitivity and paw thickness were assessed using the von Frey and Hargreaves tests, respectively. The possible cardiovascular and neurological side effects of local amiodarone injection were assessed in another set of 12 mice. In the sciatic nerve block model, amiodarone produced robust anesthesia, and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade, but not that of motor blockade [complete sensory block duration: 195.0 ± 9.8 min vs. 28.8 ± 1.3 min, F (2, 21) = 317.6, p < 0.01, complete motor block duration: 27.5 ± 1.6 min vs. 21.3 ± 2.3 min, F (2, 22) = 11.1, p = 0.0695]. In the zymosan-induced inflammatory pain model, low-dose amiodarone was effective in reversing the mechanical and thermal hypersensitivity not requiring capsaicin co-administration [50% withdrawal threshold at 8 h (g): 0.85 ± 0.09 vs. 0.25 ± 0.08, p < 0.01, withdrawal latency at 4 h (s) 8.5 ± 0.5 vs. 5.7 ± 1.4, p < 0.05]. Low-dose amiodarone did not affect zymosan-induced paw inflammation. Local amiodarone did not cause cardiovascular or central nervous system side effects. Amiodarone may have the potential to be a long-acting and nociceptor-selective local anesthetic and analgesic method acting over open-state large-pore channels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotoda, Matsuoka, Wada, Jayakar, Ino, Kawago and Kumakura.)

Introduction: Novel diagnostic and therapeutic options are urgently needed for patients with metastatic castration-resistant prostate cancer (CRPC). PSMA-617 is one of the most promising ligands that bind to prostate specific membrane antigen (PSMA), the cell surface biomarker of CRPC. Of the radiolabeled PSMA ligands developed to date, [ 68 Ga]Ga-PSMA-617 is most commonly used for PSMA positron emission tomography (PET) prior to radioligand therapy (RLT) with [ 177 Lu]Lu-PSMA-617. However, the presence of 68 Ga radioactivity (half-life 68 m) in urine at the early PET imaging time point complicates optimization of the therapeutic dose of PSMA-617 labeled with 177 Lu (half-life 6.7 d). Thus, PET imaging with the long-lived positron emitter 89 Zr (half-life 3.3 d) would be better suited in order to optimize the dose of [ 177 Lu]Lu-PSMA-617 as 89 Zr PET allows scans after excretion of the radioactive urine. Until now, PSMA-617 could not be radiolabeled with 89 Zr with high radiochemical yield due to poor incorporation of 89 Zr into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Here we report a novel method for radiolabeling PSMA-617 with 89 Zr and the preliminary results of small-animal PET with [ 89 Zr]Zr-PSMA-617., Methods: We labeled PSMA-617 with 89 Zr in a 1:1 mixture of DMSO and HEPES buffer at 90 °C for 30 min, followed by quality control analysis by HPLC. We then determined the dissociation constant (K d ) and logD values of [ 89 Zr]Zr-PSMA-617. We obtained PET images of [ 89 Zr]Zr-PSMA-617 at 24 h in mice bearing both LNCaP (PSMA-positive) and PC-3 (PSMA-negative) tumors (N = 5). The ex vivo [ 89 Zr]Zr-PSMA-617 biodistribution was then examined separately using tissue samples of LNCaP-bearing mice at 2 h (N = 4) and 24 h (N = 4)., Results: [ 89 Zr]Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The K d value was 6.8 ± 3.5 nM. The logD value was -4.05 ± 0.20. PET images showed the highest uptake in LNCaP tumors (maximum standardized uptake value, SUV max  = 0.98 ± 0.32) and low uptake in kidneys (SUV max  = 0.18 ± 0.7) due to the absence of urine radioactivity., Conclusion: [ 89 Zr]Zr-PSMA-617 was successfully prepared using DMSO and HEPES buffer. [ 89 Zr]Zr-PSMA-617 visualized PSMA-positive LNCaP tumors in the absence of radioactive urine 24 h p.i., Advances in Knowledge and Implications for Patient Care: This method of radiolabeling PSMA-617 with 89 Zr using DMSO would be suitable for future clinical trials. Prediction of radiation dose by using [ 89 Zr]Zr-PSMA-617 leads to the safe and effective RLT with [ 177 Lu]Lu-PSMA-617., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryota Imura and Hiroyuki Ida are employees of JFE Engineering Corporation. This research was partially conducted with research funds of the JFE Engineering Corporation. No other potential conflicts of interest relevant to this article exist., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The conceptualization of personal recovery began in Europe and North America and has spread worldwide. However, the concept of personal recovery in addition to recovery-promoting factors may be influenced by culture. We explored how users of mental health services in Japan perceive their own personal recovery and the factors that promote it., Methods: We conducted semi-structured interviews and focus group interviews with individuals using mental health services. The interview data were analysed using thematic analysis with a grouped framework analysis approach. We used a coding framework based on the existing CHIME framework (connectedness, hope and optimism about the future, identity, meaning in life, and empowerment)., Results: Data were obtained from 30 users of mental health services (mean age: 40.4 years; 46.7% women; 50.0% with schizophrenia). "Compassion for others" was newly extracted in "Connectedness", and "Rebuilding/redefining identity not being as shaped by social norms" was newly extracted in "Identity" as personal recovery. "Positive experiences in childhood" (including positive parenting support from neighbours) was newly extracted as a recovery-promoting factor., Conclusions: Our unique findings on the rebuilding identity/defining identity free from conformity to social norms due to interactions with familiar people, including peers, may be culture dependent. This study raises overarching questions regarding how socio-cultural values influence the development of identity and personal values and how they are in turn reflected in personal recovery., (© 2022. The Author(s).)

We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission., (© 2021. The Author(s).)

Background: Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of 18 F-DOPA to 18 F-dopamine (k 3 ) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D 2 receptor agonist (aripiprazole) on k 3 and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method., Methods: Sixty-two individuals (31 patients and 31 control subjects) underwent 18 F-DOPA positron emission tomography at baseline, and 15 patients were re-examined after 6 weeks. Clinical re-examinations were completed after 6 weeks (n = 28) and 6 months (n = 15). Symptoms were evaluated with the Positive and Negative Syndrome Scale., Results: High baseline decarboxylation rates (k 3 ) were associated with more positive symptoms at baseline (p < .001) and with symptom improvement after 6 weeks (p = .006). Subregion analyses showed that baseline k 3 for the putamen (p = .003) and nucleus accumbens (p = .013) and DSC values for the nucleus accumbens (p = .003) were associated with psychotic symptoms. The tissue reference method yielded no associations between DSC and symptoms or symptom improvement. Neither method revealed any effects of group or treatment on average magnitudes of k 3 or DSC, whereas changes in dopamine synthesis were correlated with higher baseline values, implying a potential effect of treatment., Conclusions: Striatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k 3 and treatment effect potentially implicate on new treatment strategies., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (β = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (β = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (β = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Long-term alteration of dopaminergic neurotransmission is known to modulate the D 2 /D 3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [ 11 C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Using two static scans for 123 I-meta-iodobenzyl-guanidine ( 123 I-MIBG) myocardial scintigraphy ignores the dynamic response from vesicular trapping in nerve terminals. Moreover, the long pause between scans is impractical for patients with Lewy body diseases (LBDs). Here, we optimized indices that capture norepinephrine kinetics, tested their diagnostic performance, and determined the differences in 123 I-MIBG performance among disease groups., Methods: We developed a new 30-min protocol for 123 I-MIBG dynamic planar imaging for suspected LBD patients. Pharmacokinetic modelling of time-activity curves (TACs) was used to calculate three new indices: unidirectional uptake of 123 I-MIBG to vesicular trapping (iUp), rate of myocardial 123 I-MIBG loss (iLoss), and non-specific fractional distribution of 123 I-MIBG in the interstitial space. We compared the performance of the new and existing indices with regard to discrimination of patients with or without LBDs. Subgroup analysis was performed to examine differences in 123 I-MIBG turnover between patients in a dementia with Lewy bodies (DLB) group and two Parkinson's disease (PD) groups, one with and the other without REM sleep behaviour disorder (RBD)., Results: iLoss was highly discriminative, particularly for patients with low myocardial 123 I-MIBG trapping, and the new indices outperformed existing ones. ROC analysis revealed that the AUC of iLoss (0.903) was significantly higher than that of early HMR (0.863), while comparable to that of delayed HMR (0.892). The RBD-positive PD group and the DLB group had higher turnover rates than the RBD-negative PD group, indicating a potential association between prognosis and iLoss., Conclusion: 123 I-MIBG turnover can be quantified in 30 min using a three-parameter model based on 123 I-MIBG TACs. The discriminatory performance of the new model-based indices might help explain the neurotoxicity or neurodegeneration that occurs in LBD patients., (© 2021. The Author(s).)

Introduction: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events., Methods: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events., Results: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events., Conclusions: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings., Trial Registration Number: UMIN 000044282 (University Hospital Medical Information Network)., (© 2021. The Author(s).)

Aim: Psychiatric disturbances are the major adverse effects of corticosteroids. There are no consistent conclusions regarding changes in steroid dosage and the incidence of psychiatric conditions, due in part to the lack of consistent evaluation criteria. The purpose of this research was to determine the incidence and dose-dependency of psychiatric conditions as assessed by trained psychiatrists., Methods: A retrospective chart review was conducted at a university hospital in Japan. We identified inpatients receiving oral prednisolone treatment, who were referred to the consultation-liaison psychiatry team from April 2015 to March 2018. Patients were divided into high-dose (≥0.5 mg/kg/day) and low-dose (<0.5 mg/kg/day) groups. We investigated the associations between steroid dosage and incidence of psychiatric conditions., Results: A total of 93 patients (35 in the high-dose group, 58 in the low-dose group) were included. Various psychiatric conditions, such as insomnia, delirium, depression, and psychosis, occurred during steroid therapy. The most common condition was insomnia (72%). We observed no significant differences in the patient background characteristics and the incidence of most psychiatric conditions between the high-dose and low-dose groups. However, there were more patients with delirium in the low-dose group than in the high-dose group., Conclusions: Based on the accurate assessment of psychiatric conditions by psychiatrists, our analysis suggests that, among inpatients referred to a consultation-liaison psychiatry team, the incidence of psychiatric conditions, with the exception of delirium, is independent of the dose of oral prednisolone., (© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background and Aim: Long-term cumulative incidence of and risk factors for metachronous advanced colorectal neoplasia, including both advanced colorectal adenoma (≥10 mm, or with villous or high-grade dysplasia) and colorectal cancer, are critical for surveillance strategies. The aim of this study was to determine the cumulative incidence of metachronous advanced colorectal neoplasia and its risk factors., Methods: A retrospective cohort study was conducted on 6720 consecutive individuals who underwent general health check-ups and colonoscopy. Colorectal adenomas at initial colonoscopy were categorized as low-risk (1-2 small [<10 mm] tubular adenomas) or high-risk adenoma (≥3 tubular adenomas of any size; at least one adenoma ≥10 mm; or villous adenoma or adenoma with high-grade dysplasia). Kaplan-Meier estimates and hazard ratio by Cox-proportional hazard regression were calculated., Results: The cumulative incidence (95% confidence interval [CI]) of metachronous advanced colorectal neoplasia at 5 and 10 years was 5.7% [4.6-7.1], and 11% [8.9-14] in the low-risk adenoma group, and 10% [8.6-13], and 17% [14-21] in high-risk adenoma group, respectively. Adjusted hazard ratio [95% CI] of low-risk adenoma (vs. no colorectal adenoma), high-risk adenoma (vs. no colorectal adenoma), current smoking and positive fecal immunochemical test were 1.34 [1.04-1.74], 1.94 [1.48-2.55], 1.55 [1.2-2.02] and 1.69 [1.35-2.1], respectively. Adjusted hazard ratio [95% CI] of positive fecal immunochemical test was 1.88 [1.29-2.74] in those with normal colonoscopy., Conclusions: Both low-risk and high-risk adenomas confer substantial risk for metachronous advanced colorectal neoplasia at 10 years. Positive fecal immunochemical test was a significant risk factor for metachronous advanced colorectal neoplasia despite normal colonoscopy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vertebral compression fractures can cause severe back pain. Although many types of analgesics and interventional treatments are available, they are sometimes ineffective in mitigating the pain. We encountered a case where clonazepam was effective for the management of severe low back pain caused by lumbar vertebral compression fractures., Case Presentation: A 44-year-old male was diagnosed with multiple myeloma and had vertebral compression fractures of the first and second lumbar vertebrae. He had been suffering from severe low back pain on movement with muscle spasm and pain-associated anxiety. We considered this breakthrough low back pain to be caused by facet joint pain; thus, we prescribed clonazepam as a muscle relaxant and anxiolytic. Following this treatment, the intractable breakthrough pain was dramatically relieved., Conclusion: Clonazepam, which has both muscle relaxant and anxiolytic effects, might be helpful in mitigating pain, associated anxiety, and muscle spasms due to vertebral compression fractures., (© 2021. The Author(s).)

Background: Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. CD36, a long-chain fatty acid (FA) receptor, can initiate metastasis in human oral squamous cell carcinoma (SCC), and its expression is associated with poor prognosis in several cancers. The clinical significance of CD36 expression and its function in ESCC remain unknown., Methods: We examined the clinical significance of CD36 expression in 160 ESCC samples using immunohistochemical staining. Functional analysis was performed to determine the association between CD36 and ESCC characteristics (proliferative ability, invasive ability, and energy source dependency)., Results: Thirty (18.8%) ESCC cases showed high CD36 expression, indicating a significant association with progression. CD36 suppression inhibited proliferation and invasiveness in ESCC cells. ESCC cells with CD36 suppression used specific essential amino acids (EAAs) as energy sources. Cell viability depended on FAs under CD36 expression. The viability of ESCC cells with CD36 suppression depended on EAAs but not FAs., Conclusions: CD36 may be a good biomarker and therapeutic target in ESCC. Our data provide new insights into the basic mechanism of CD36-dependent energy utilization for ESCC survival. CD36 might be a key regulator of the dependency of FAs as energy source in ESCC cells.

Purpose: To evaluate changes in cerebral regional oxygen saturation (rSO 2 ) after spinal anesthesia and compare the changes in rSO 2 and systemic oxygenation between dexmedetomidine sedation and propofol sedation., Methods: Thirty-six patients scheduled to undergo transurethral surgery under spinal anesthesia were randomly assigned to the dexmedetomidine (n = 18) and propofol groups (n = 18). We used near-infrared spectroscopy sensors to measure rSO 2 , and obtained data from each side were averaged. After oxygen insufflation, baseline measurements of mean arterial blood pressure (MAP), heart rate, rSO 2 , pulse oximetry saturation (SpO 2 ), bispectral index, and body temperature were made. After spinal anesthesia, we measured these parameters every 5 min. Twenty minutes after spinal injection, dexmedetomidine or propofol administration was started. We measured each parameter at 10, 25, and 40 min after the administration of dexmedetomidine or propofol., Results: The baseline rSO 2 in the dexmedetomidine group was 71.3 ± 7.3%, and that in the propofol group was 71.8 ± 5.6%. After spinal anesthesia, rSO 2 in both groups decreased significantly (dexmedetomidine group: 65.4 ± 6.9%; propofol group: 64.3 ± 7.4%). After administering sedatives, rSO 2 was equivalent after spinal anesthesia. rSO 2 was comparable between the two groups. MAP and SpO 2 were significantly higher in the dexmedetomidine group than in the propofol group., Conclusion: Spinal anesthesia decreased rSO 2 ; however, the decline was not severe. Dexmedetomidine and propofol did not compromise cerebral oxygenation under spinal anesthesia. Nevertheless, MAP and SpO 2 were more stable in dexmedetomidine sedation than in propofol sedation. Dexmedetomidine may be suitable for spinal anesthesia.

Although the "stay-at-home" order is advocated against the coronavirus disease 2019 (COVID-19), the lives of individuals lacking adequate housing are threatened. We developed a framework to assess various populations with unstable housing in terms of socio-economic consequences of COVID-19, risk of COVID-19 infection and progression, existing/urgent measures, and remaining challenges. Within the framework, nine groups vulnerable to homelessness in Japan were classified into (i) "people without accommodation," (ii) "people living in temporary or crisis accommodation," and (iii) populations that include "people living in severely inadequate and insecure accommodation." The assessment revealed that "staying at home" was physically and practically unattainable across groups. The study identified specific institutional, social, and cultural challenges apart from the common economic crisis, whereas the utilization of social welfare was low. Findings suggest that the rapid increase of groups classified as "(i)" and "(ii)" should be addressed by engaging stakeholders to enhance the availability and accessibility of social welfare and rescue measures, and to ensure safe and private accommodations for all groups. It is critical to enhance multi-sectoral collaboration in responding to the common and specific vulnerabilities of these population groups from health, socio-economic, and humanitarian perspectives. Under the pandemic, homelessness should be regarded less as a peculiar problem for specific populations but an extension of daily life. The framework can be a reference when planning the comprehensive yet concise assessment of populations with unstable housing in other countries to inform responses to the pandemic.

Background and Aims: Boerhaave's syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated., Methods: We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism., Results: We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1-4 cm) and located in the left of the esophagus, just above the gastric cardia., Conclusions: We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave's syndrome is defined as "post-emetic esophageal perforation" to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled "idiopathic" or "spontaneous" rupture of the esophagus.

Background: Antispasmodics, such as scopolamine, are widely used in several countries prior to diagnostic and screening esophagogastroduodenoscopy (EGD), with the goal of optimizing the detection of minute lesions, typically early gastric cancer (T1 lesions). The aim of this study was to determine whether scopolamine facilitates detection of gastric cancer in the screening setting., Methods: A propensity score-matched retrospective study was conducted in a tertiary referral medical center in Tokyo, Japan. Consecutive individuals (n = 40 776) underwent screening EGD between January 2011 and May 2016. All outcome lesions were diagnosed with histopathological confirmation. Detection of esophageal cancer, gastric adenoma, duodenal adenoma, and upper gastrointestinal neoplasia (UGIN) were investigated as secondary outcomes., Results: Scopolamine was used in 31 130 patients (76.3 %) and propensity score matching yielded 6625 pairs. Bivariate analysis revealed no significant association between possible confounders (age, sex, overweight, atrophic gastritis, alcohol history, smoking history, midazolam use, endoscopist biopsy rate grade, and gastric cancer in first-degree relatives) and scopolamine use. Lesions detected were 18 gastric cancers, 11 esophageal cancers, 19 gastric adenomas, 6 duodenal adenomas, and 54 UGINs, with no significant association between scopolamine use and lesion detection., Conclusions: Scopolamine use did not appear to effectively facilitate detection of gastric or esophageal cancer, gastric or duodenal adenoma, and UGIN during screening EGD. Scopolamine should be avoided until its efficacy is confirmed by a randomized controlled trial., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Supporting personal recovery in people with mental health difficulties is central to mental health services. This study aimed to develop the Japanese version of INSPIRE and Brief INSPIRE measure of staff support for personal recovery and to evaluate its reliability and validity., Methods: A questionnaire survey was conducted from October to December 2015. The authors asked users to participate in the survey of 14 community mental health services in the Kanto region of Japan. The service users completed self-administered questionnaires that include the Japanese version of INSPIRE, the Recovery Assessment Scale, the Client Satisfaction Questionnaire, the patient version of the Scale to Assess Therapeutic Relationship in Community Mental Health care and the Short Form Health Survey. Internal consistency was assessed using Cronbach's alpha coefficient, and test-retest reliability was assessed using the intraclass correlation coefficient (ICC) and weighted kappa. Convergent validity was examined by assessing correlation with other scales. Factor validity was evaluated by exploratory factor analysis (EFA) with generalized least-squares mean and oblimin rotation. In addition, confirmatory factor analysis was used to check the fitness of the factor structure models derived from the EFA., Results: A total of 195 out of 212 users gave written informed consent and participated in the study. Data from 190 respondents were analyzed (response rate 89.6%). INSPIRE, Brief INSPIRE, and the subscales all showed Cronbach's alpha coefficient over 0.78. ICC and weighted kappa derived more than 0.92 for subscales and Brief INSPIRE. These numerical values indicated good reliability. The convergent validity of Brief INSPIRE and the subscales was significantly positively correlated with the other scales. Different from the previous study, the factor structure was extracted using EFA. Both factor structures were checked by CFA, but the degree of fitness index was not good in either. Therefore, the factor analysis did not show goodness of fit., Conclusions: This study found the Japanese version of INSPIRE and Brief INSPIRE to be reliable and valid for use among community mental health service users in Japan.

Background: Endoscopic submucosal dissection (ESD) of superficial esophageal cancer has been used increasingly as an alternative to surgery because it is minimally invasive and has a high rate of en bloc resection. We previously reported that the double endoscopic intraluminal operation (DEILO) is a useful technique for ESD of early esophageal cancers. In the current study, we showed comparable short-term data between DEILO and conventional ESD groups to demonstrate the further advanced use of DEILO., Methods: We studied 111 esophageal cancer patients with 111 lesions treated using endoscopic surgery between January 2010 and June 2016 at Gunma University Hospital. Of the patients, 51 underwent DEILO (DEILO group) and 60 underwent conventional ESD (ESD group). We compared the operable performance, complications, and pathological outcome between the ESD and DEILO groups., Results: There was no significant difference in operable performance. However, the DEILO group showed a significantly lower rate of mediastinal emphysema compared to the ESD group (p = 0.025). Overall, the DEILO group showed a lower complication rate compared to the ESD group, although there was no apparent significance., Conclusion: To our knowledge, this is the first report comparing DEILO and conventional ESD for esophageal cancer. The results showed that DEILO is not inferior to conventional ESD. DEILO is an excellent endoscopic surgical method, although it has some limitations compared to conventional ESD.

Background : Anastomotic leakage after esophagectomy is significantly associated with more severe complications, such as sepsis and mortality. Early prediction for anastomotic leakage is usually difficult and needs to be treated rapidly. In the current study, we investigated the correlation between hemodynamic and several complications after esophagectomy in patients with esophageal cancer, using the FloTrac system. Materials and Methods : Between April 2013 and December 2014, 39 patients with a mean age of 66.6 ± 8.9 years underwent postoperative supervision using the FloTrac sensor / Vigileo monitoring system after curative surgery for esophageal cancer. We retrospectively evaluated the association between the number of aberrant cardiac index (CI) along with stroke volume variability (SVV) values and clinicopathological parameters of postoperative complications in this report. Results : There were significant positive correlations between the number of aberrant values of CI along with SVV and depth of invasion during pathological stage. Concerning major postoperative complications, there was a significant positive correlation between the number of aberrant values of CI and anastomotic leakage. Discussion: The hemodynamic change by employing the FloTrac system could predicts the complication of anastomotic leakage after esophagectomy. Adequate management of hemodynamic stability by utilizing it will reduce the complications of anastomotic leakage. J. Med. Invest. 67 : 240-245, August, 2020.

Background/aim: Esophagectomy is more invasive compared to other gastrointestinal surgery types. Perioperative circulatory management is important to avoid postoperative heart complications. The FloTrac sensor along with the Vigileo monitor is a minimally invasive haemodynamic monitoring device. Here, we examined different surgical procedures affecting hemodynamics using the FloTrac system in esophageal cancer patients following esophagectomy., Patients and Methods: Thirty-one patients undergoing postoperative monitoring with the FloTrac sensor/Vigileo monitor system following esophagectomy were included. Evaluation of cardiac index (CI) and stroke volume variation (SVV) measurements were performed by analyzing the number of aberrant values. We evaluated the correlation between the number of aberrant values of CI, SVV and surgical methods of esophagectomy and perioperative factors., Results: There was no significant correlation between the number of aberrant values of CI, SVV and operative approach or fields of lymphadenectomy. Regarding the reconstruction route following esophagectomy, there was a significant correlation between the number of aberrant values of CI, SVV and retrosternal route compared with other routes. There was a significant correlation between the number of aberrant values of SVV and preoperative heart complication., Conclusion: Hemodynamic stability management using FloTrac/Vigileo system following esophagectomy is useful for safe performance of postoperative management of esophageal cancer patients., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for cervical esophageal cancer (CEC), we performed a retrospective analysis of CEC patients treated by DCF-RT at a single institution., Methods: We conducted a single-center retrospective study. Twenty-one patients with CEC who underwent DCF-RT between 1999 and 2017 at our institute were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m 2 on day 1, intravenous CDDP at 60 mg/m 2 on day 1, and intravenous 5-FU at 600 mg/m 2 on days 1-4, repeated every 4 weeks for two cycles. Among the 21 patients, six were irradiated using three-dimensional conformal RT (3D- conformal RT) and 15 were treated using intensity-modulated RT (IMRT) consisting of 60 Gy in 30 fractions., Results: The median follow-up period was 49.6 months (range 4.6-97.6). The overall complete response (CR) and local CR rates were 61.9% and 81.0% for all patients, and 76.9% and 84.6% for patients without hypopharyngeal and/or thoracic esophageal invasion, respectively. The 3-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 79.6, 52.4, and 74.7%, respectively. Grade 3-4 leucopenia developed in 12 patients (70.6%), neutropenia developed in 13 patients (81.2%), and mucositis developed in 2 patients (9.5%). There were no treatment-related deaths., Conclusions: The 3-year OS and LFFS of patients who underwent DCF-RT were higher than those in the previous studies. Although the high rate of myelosuppression requires careful management, DCF-RT is a safe and effective modality for CEC.

Background/aim: Unresectable oesophageal cancer with surrounding invasion carries a particularly poor prognosis. The chemoradiotherapy treatment for locally-unresectable oesophageal cancer aims to initially control local invasion before proceeding to the next treatment, and is ideally used with curative intent. The aim of this study was to investigate patient treatment course and survival to determine the best treatment and evaluate surgical intervention for these advanced cancers., Patients and Methods: A total of 147 patients who were diagnosed with clinical T4b oesophageal cancer were included in this study., Results: Forty-three patients had undergone curative resection of the tumour and surrounding invasion at midterm evaluation, 104 patients continued with definitive chemoradiotherapy, and salvage surgery was performed in 21 patients. Multivariate analysis of disease-specific survival showed that response at the midterm evaluation and surgical intervention (conversion surgery + salvage surgery) were significant prognostic factors., Conclusion: Surgical intervention was an independent prognostic factor, and operation should be performed in eligible patients after considering the risks and proper timing., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Postoperative chemotherapy is an absolutely imperative treatment for advanced esophageal cancer patients, while preoperative chemotherapy is the standard therapy for clinical stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to report the effect of postoperative chemotherapy on survival after esophagectomy due to thoracic esophageal squamous cell carcinoma., Patients and Methods: One hundred thirteen consecutive patients with esophageal carcinoma who underwent esophagectomy were included. Several regiments were performed at various times., Results: Adjuvant chemotherapy brought a significantly superior overall survival (p=0.002), although there was no significant difference in cancer-specific survival (p=0.054) for clinical stage II or stage III esophageal cancer patients. Depth of invasion (p=0.003), number of lymph node metastases (p=0.048), and venous invasion (p<0.001) were risk factors for recurrence in the adjuvant-chemotherapy group with positive lymph nodes. Additionally, a not well-differentiated type, lymphatic and venous invasions were risk factors for recurrence in the surgery-alone group without positive lymph nodes., Conclusion: Postoperative adjuvant chemotherapy contributes to the prognosis of clinical stage II or III esophageal cancer patients., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

High-resolution manometry (HRM) has significant contribution in the field of esophageal motility disorders recently. The development of HRM has categorized various esophageal motility disorders focusing on patterns of esophageal motor function. Additionally, the Chicago classification criteria are widely used for manometric diagnosis. HRM provides functional imaging of the esophagus. HRM has closely spaced pressure sensors and displays pressure variations as pressure topography plots. In the analysis of HRM according to the Chicago classification, a hierarchical categorization of motility disorders is made after evaluation of the individual swallow patterns. First the lower esophageal sphincter (LES) function, and subsequently the esophageal pressure patterns are used to make a diagnosis. The hierarchical flow-chart has 4 groups; (1) incomplete LES relaxation( achalasia or esophagogastric junction outflow obstruction), (2) major motility disorders, (3) minor motility disorders, (4) normal esophageal motility. HRM is the gold standard for diagnosis of esophageal motility disorders.

A 50-year-old man who presented with a fever and epigastralgia was diagnosed to have esophageal carcinoma which was identified as poorly differentiated adenocarcinoma producing alpha-fetoprotein (AFP) with Barrett's esophagus. Computed tomography revealed multiple liver metastases and lymph node metastases surrounding the stomach. We first performed chemotherapy for the systemic lesions and proton beam therapy for the local control of lesions without complete remission and we were able to successfully control the frequently recurring lesions by proton beam therapy, cryotherapy and chemotherapy. A complete response has been maintained for 16 months and the overall survival time is 4 years and 2 months. Proton beam therapy for primary esophageal cancer and metastatic lesions was thus found to be an effective therapeutic option for such cases.

Background and Objectives: Esophageal squamous cell carcinoma (ESCC) exhibits good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance in cancer cells. However, the correlation between FBXW7 expression and CRT sensitivity in patients with clinical ESCC has been investigated only in few studies. Therefore, this study aimed to elucidate the significance of FBXW7 expression in pretreatment biopsy specimens from patients with ESCC receiving CRT., Methods: We investigated the relationship between FBXW7 expression and CRT sensitivity in 30 pretreatment biopsy specimens with histological grades of post-CRT surgically resected tumors. Furthermore, we evaluated the effects of high FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and nedaplatin, and radiation in ESCC cells in vitro., Results: High FBXW7 expression before CRT correlated with a good pathological CRT response in patients with advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1., Conclusions: The evaluation of FBXW7 expression before CRT treatment is a potential predictor of good responders among patients with ESCC receiving CRT., (© 2018 Wiley Periodicals, Inc.)

Background: Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus., Methods: We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae)., Results: The frequency of LNM to the middle mediastinal and supraclavicular zones, including the Mt and Ce, respectively, was lower than to the upper and lower mediastinal and abdominal zone in patients with superficial and advanced thoracic ESCC. In cadavers, the lymphatic vessel counts of the intra-outer longitudinal muscle layer in the Mt and Ce were significantly lower than those of the Lt and Ae, suggesting that lymphatic flow toward the outside of the Mt and Ce was not more abundant than to other sites., Conclusion: Our anatomical data suggested that the absence of intra-muscle lymphatic vessels in the middle mediastinal and supraclavicular zones causes skip LNM in patients with thoracic ESCC. Thus, standard esophagectomy with lymph node dissection, including distant zones, may be appropriate for treating patients with superficial thoracic ESCC.

We investigated the association between CYP2C19 genotype and additional effect of cilostazol on clopidogrel resistance (CR) in neuroendovascular therapy. Between January 2012 and January 2016, 447 consecutive patients were administered with 75-mg cilostazol/day. The VerifyNow System was used for evaluating P2Y12 reaction units (PRU) > 230 and/or percentage inhibition of platelet function (% Inhibition) ≤ 20 as CR. Among 158 patients with CR, 31 were administered with additional 100- or 200-mg cilostazol/day and their platelet function was evaluated. According to CYP2C19 genotypes revealed using the Spartan RX and DNeasy Blood & Tissue Kit, patients were classified into three phenotypic groups: extensive metabolizer (EM, three patients), intermediate metabolizer (IM, 12 patients), and poor metabolizer (PM, 16 patients). Administration of additional cilostazol decreased PRU (EM group: 160.7 ± 85.2 after vs 278.3 ± 40.1 before, P = 0.15; IM group: 205.6 ± 74.0 vs 254.3 ± 35.0, P = 0.02; and PM group: 227.8 ± 52.2 vs 282.1 ± 30.4, P = 0.003), and increased % Inhibition (EM group: 40.0 ± 27.9 vs 9.3 ± 3.8, P = 0.25; IM group: 31.4 ± 18.0 vs 11.8 ± 8.2, P = 0.001; and PM group: 24.6 ± 15.0 vs 10.4 ± 9.3, P = 0.001). However, the rate of normalized-clopidogrel response, thromboembolic lesions, and bleeding complications were not significantly different among the three groups. Thus, the addition of cilostazol was effective on CR in terms of PRU, % Inhibition, rate of change of normalized-clopidogrel response, thromboembolic events, and bleeding complications irrespective of phenotype.

Archaea and eukaryotes have ribosomal P stalks composed of anchor protein P0 and aP1 homodimers (archaea) or P1•P2 heterodimers (eukaryotes). These P stalks recruit translational GTPases to the GTPase-associated center in ribosomes to provide energy during translation. The C-terminus of the P stalk is known to selectively recognize GTPases. Here we investigated the interaction between the P stalk and elongation factor 2 by determining the structures of Pyrococcus horikoshii EF-2 (PhoEF-2) in the Apo-form, GDP-form, GMPPCP-form (GTP-form), and GMPPCP-form bound with 11 C-terminal residues of P1 (P1C11). Helical structured P1C11 binds to a hydrophobic groove between domain G and subdomain G' of PhoEF-2, where is completely different from that of aEF-1α in terms of both position and sequence, implying that such interaction characteristic may be requested by how GTPases perform their functions on the ribosome. Combining PhoEF-2 P1-binding assays with a structural comparison of current PhoEF-2 structures and molecular dynamics model of a P1C11-bound GDP form, the conformational changes of the P1C11-binding groove in each form suggest that in response to the translation process, the groove has three states: closed, open, and release for recruiting and releasing GTPases.

The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen ( CEA ), human Telomerase Reverse Transcriptase ( hTERT ), cytokeratin19 ( CK19 ), and programmed death ligand-1 ( PD-L1 ) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab. The CTC chip effectively enriched cells from lung cancer cell line PC-9. The large cell fraction had a high expression of CEA and hTERT , with the former being significantly associated with the clinical response to nivolumab. The expression of CEA and hTERT in CTCs derived from the blood of a patient with lung cancer were also validated. The evaluation of CEA and possibly hTERT in CTCs collected by the CTC chip may represent a promising predictive blood marker for sensitivity to nivolumab. To the best of our knowledge this is the first report to describe the predictive CTC marker for nivolumab in pre-treatment patients.

Background: To investigate whether malnutrition is associated with poor prognosis of patients who undergo salvage esophagectomy. We examined the association between the preoperative prognostic nutritional index (PNI) and prognosis of patients who undergo salvage esophagectomy., Patients and Methods: We conducted a single-center retrospective study and reviewed hospital patient records for tumor characteristics and patient outcomes. Univariate and multivariate survival analyses were carried out using the Cox proportional hazards regression model., Results: Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who underwent salvage esophagectomy between 1998 and 2015 at our Institute were included in this study. Univariate analysis revealed that clinical response (p=0.045), preoperative PNI (p<0.001), pT (p=0.024), pN (p=0.004), and residual tumors (p<0.001) were significant prognostic factor for overall survival. Multivariate analysis using age and these five variables found no independent prognostic factors. Multivariate analysis using three preoperative variables (age, clinical response, and preoperative PNI) revealed that PNI was an independent prognostic preoperative factor for overall survival (p=0.005)., Conclusion: Preoperative nutritional status is associated with the prognosis of patients undergoing salvage esophagectomy., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Hiatal hernias are common. In some reports, hiatal hernias have been implicated in causing dyspnea, syncope, and heart failure., Case Presentation: An 82-year-old woman with a hiatal hernia was admitted to our hospital because she had experienced postprandial syncope during the last few years. Esophagogastroduodenoscopy revealed a large hiatal hernia and a pedunculated polyp of the stomach antrum that fit into the pylorus. An upper gastrointestinal contrast study showed that the entire stomach had relocated to the thoracic cavity and that the body of the stomach was located above the fundus, resulting in a so-called upside-down stomach. Contrast-enhanced computed tomography revealed that a large portion of the stomach, transverse colon, and part of the pancreas were present in the mediastinum. We then performed transthoracic echocardiography followed by a water pouring test using a nasogastric tube. After instillation of 2000 ml of saline, the left atrium was markedly compressed and the area of the mitral annulus was reduced. We determined that stomach dilation by the hiatal hernia and gastric polyp had caused the syncope. The patient underwent laparoscopic hiatal hernia repair and endoscopic gastric polypectomy, and she experienced no syncopal episodes for 5 months postoperatively., Conclusions: Clinicians should recognize that a large hiatal hernia may be a risk factor for syncope.

Background: The right gastroepiploic artery is commonly used in coronary artery bypass grafting. Appropriate strategies are required when performing upper abdominal surgeries after the right gastroepiploic artery has been used in coronary artery bypass grafting because compressing or injuring the graft may cause myocardial ischemia and fatal arrhythmias. To our knowledge, this is the first reported case of surgery for achalasia performed after coronary artery bypass grafting using the right gastroepiploic artery. We have discussed the surgical procedure and particular intraoperative considerations., Case Presentation: A 62-year-old man who had undergone coronary artery bypass grafting using the right gastroepiploic artery presented with achalasia. Because medication and balloon dilation had been ineffective and he was having difficulty ingesting food, we performed a Heller-Dor procedure via laparotomy. The right gastroepiploic artery was not damaged during this surgery, and there were no perioperative cardiovascular complications. Adequate control of symptoms was achieved., Conclusions: When performing upper abdominal surgeries after coronary artery bypass grafting with the right gastroepiploic artery, it is necessary to investigate the patient carefully preoperatively and adapt the intraoperative procedure to minimize risk of injury to the graft and consequent cardiovascular complications.