Laparoscopic proximal gastrectomy with double-flap technique versus laparoscopic subtotal gastrectomy for proximal early gastric cancer.

BACKGROUND: Laparoscopic proximal gastrectomy with double-flap technique (LPG-DFT) and laparoscopic subtotal gastrectomy (LSTG) may replace laparoscopic total gastrectomy (LTG) for proximal early gastric cancer. The aim of this study was to evaluate short- and long-term outcomes after LPG-DFT and LSTG. METHODS: Patients who underwent LPG-DFT or LSTG at the Cancer Institute Hospital in Tokyo between January 2006 and April 2015 were included in this retrospective study. Operative procedures were selected based on the distance from the cardia to the proximal boundary of the tumour, tumour location and predicted remnant stomach volume. Patient characteristics, surgical data, markers of postoperative nutritional status, such as blood chemistry and bodyweight loss, and endoscopic findings were compared between procedures. The main study outcome was nutritional status. RESULTS: A total of 161 patients (LPG-DFT 51, LSTG 110) were included. Types of postoperative complication occurring more than 30 days after surgery differed between the two procedures. Remnant stomach ulcers, including anastomotic ulcers, were observed only after LPG-DFT, whereas complications involving the small intestine, such as internal hernia or small bowel obstruction, occurred more frequently after LSTG. Values for total protein, albumin, prealbumin and bodyweight loss were comparable between the two procedures at 36 months after surgery. Haemoglobin concentrations were higher after LPG-DFT than after LSTG at 24 months (13·4 versus 12·8 g/dl respectively; P = 0·045) and 36 months (13·5 versus 12·8 g/dl; P = 0·007) after surgery. The rate of Los Angeles grade B or more severe reflux oesophagitis was comparable. CONCLUSION: LPG-DFT and LSTG for proximal early gastric cancer have similar outcomes, but different types of complication.

ANTECEDENTES: La gastrectomía proximal laparoscópica con técnica de doble derivación (double flap technique, LPG-DFT) y la gastrectomía subtotal laparoscópica (laparoscopic subtotal gastrectomy, LsTG) pueden sustituir a la gastrectomía total laparoscópica (laparoscopic total gastrectomy, LTG) para el cáncer gástrico precoz (early gastric cancer, EGC) proximal. El objetivo de este estudio fue evaluar los resultados a corto y a largo plazo tras LPG-DFT y LsTG. MÉTODOS: En este estudio retrospectivo se incluyeron pacientes que fueron sometidos a LPG-DFT o LsTG en el Hospital del Instituto del Cáncer de Tokio entre enero 2006 y abril 2015. Las técnicas quirúrgicas se seleccionaron en base a la distancia entre el cardias y el borde proximal del tumor, localización del tumor, y el volumen previsto del remanente gástrico. Las características de los pacientes, datos quirúrgicos, marcadores del estado nutricional postoperatorio, tales como la bioquímica sanguínea y la pérdida de peso corporal (body weight loss, BWL), y los hallazgos endoscópicos se compararon entre las técnicas. El resultado principal del estudio fue el estado nutricional. RESULTADOS: Se incluyeron un total de 161 pacientes (LPG-DFT 51, LsTG 110). Los tipos de complicaciones postoperatorias que aparecieron a más de 30 días después de la cirugía variaron entre ambas técnicas. Las úlceras en el remanente gástrico, incluyendo úlceras anastomóticas, solo se observaron tras una LPG-DFT, mientras las complicaciones relacionadas con el intestino delgado, como la hernia interna o la obstrucción de intestino delgado, sucedió con más frecuencia tras una LsTG. Los valores de proteínas totales, albúmina, prealbúmina, y BWL fueron comparables entre ambas técnicas a los 36 meses después de la cirugía. Las concentraciones de hemoglobina fueron más altas tras una LPG-DFT que tras una LsTG a los 24 (13,4 versus 12,8 mg/dL, P = 0,045) y 36 meses (13,5 versus 12,8 mg/mL, P = 0,007) después de la cirugía. Las incidencias de esofagitis por reflujo grado B Los Angeles o más grave fueron comparables. CONCLUSIÓN: La LPG-DFT y la LsTG para el EGC proximal presentan resultados bastante similares, pero difieren en el tipo de complicaciones.

Effect of Systematic Conversion to Generic Mycophenolate Mofetil (MMF) in Kidney Transplantation: A Single-Center Clinical Experience from Japan.

INTRODUCTION: Recently, more and more generic drugs have been used for immunosuppressive drugs in the field of organ transplantation. Some reports have indicated that blood concentration of most generic drugs is difficult to maintain stability, and it may cause the difference in graft survival of transplanted organs between original drugs and generic drugs. In this article, we report the cases could not maintain blood concentration of generic drugs of mycophenolate mofetil (MMF). RESULTS: In 4 cases out of 5 cases that we had to change original MMF to generic MMF, there were cases that blood concentration level was not stabilized. There were possibility that the lowered blood concentration level of MMF caused a rejection, in two cases. Mean MMF trough level was decreased from 3.6 ± 1.9 µg/mL to 0.6 ± 0.4 µg/mL. Due to the early detection, it did not become severe or failure of graft function, however, we cannot deny the possibilities that side effects were increased and rejection rose. In these cases, we discontinued to use the generic drugs thereafter due to unstable plasma concentration of MMF. DISCUSSION: Some reports have indicated that failure to maintain plasma concentration of MMF leads to rejection. Therefore, maintenance of effective plasma concentration and prevention of rejection are essential to long-term graft survival in kidney transplant. CONCLUSION: Generic drug formulations may exhibit differences in effects and absorption compared to the brand-name drug. If the generic drug should be used, patients should be closely monitored.

Azathioprine-induced Agranulocytosis and Severe Alopecia After Kidney Transplantation Associated With a NUDT15 Polymorphism: A Case Report.

BACKGROUND: Azathioprine (AZA) is the drug recommended for the continuation of immunosuppressive treatment after renal transplant in women during pregnancy. CASE REPORT: A 37-year-old Japanese female developed agranulocytosis and severe alopecia after initiation of AZA (50 mg), used as an alternative to mycophenolate mofetil (MMF, 1000 mg) therapy in anticipation of a planned pregnancy. Within 4 days of the initiation of AZA therapy, the patient developed a high fever, leucopenia, and cranial alopecia. Genetic testing revealed a homozygous polymorphism of NUDT15 (rs116855232, NM_018283.3:c.415C>T: p.Arg139Cys), which has previously been identified as a risk factor for AZA-related complications in patients with inflammatory bowel disease. CONCLUSION: Genetic screening for NUDT15 could contribute to the prevention of serious adverse reactions to AZA and provide the opportunity for personalized medicine. Identification of a safe alternative to MMF during pregnancy after a renal transplant is a problem to be resolved in the future.

The Relation between Asthma Control and Quality of Life in Children.

BACKGROUND: Asthma is a common chronic illness worldwide. Asthmatic children are forced to alter their way of living to avoid its complications or exacerbations, which negatively affects their psychological and social well-being. High prevalence of behavioral and emotional difficulties was noticed among children with asthma. METHODS: Cross-sectional study that was conducted over 8 months involving asthmatic children within the ages of 7-17 years presenting to two governmental hospitals in Jeddah, Saudi Arabia. Three questionnaires were used: asthma control test, the strengths and difficulties questionnaire, and the pediatrics asthma quality of life questionnaire. Using SPSS, Pearson's chi-square and independent sample t-tests were used to find associations. RESULTS: Among the 106 respondents, 84% of the sample had poor asthma control. Significantly poorer quality of life was observed in children with uncontrolled asthma (p = <0.001). Children with controlled and uncontrolled asthma were equally affected psychosocially with no relation between asthma control and their psychosocial well-being (p = 0.58). CONCLUSION: The majority of asthmatic children were uncontrolled with poor quality of life. This study recommends that the psychosocial well-being should be assessed during clinic visits for a better holistic approach and effective improvement of outcome. Further researches are needed to study the psychological effect of asthma.

Longitudinal analysis of antibody profiles against plakins in severe drug eruptions: emphasis on correlation with tissue damage in drug-induced hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms.

BACKGROUND: The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. OBJECTIVES: To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. METHODS: We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. RESULTS: AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. CONCLUSIONS: These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses.

Trends in psychological distress and alcoholism after The Great East Japan Earthquake of 2011.

AIMS: Many studies have shown that natural disasters affect mental health; however, longitudinal data on post-disaster mental health problems are scarce. The aims of our study were to investigate the trend in psychological distress and alcoholism after The Great East Japan Earthquake and tsunami in north eastern Japan, in March 2011. METHODS: A longitudinal study was conducted using annual health check data for the general population, in the city of Higashi-Matsushima, which was affected by the high impact of tsunami. In 2012 and 2013, the Kessler Psychological Distress Scale and the CAGE questionnaire (for screening for alcoholism) were used to assess psychological distress and prevalence of alcoholism. RESULTS: Of 11,855 total eligible residents, 2192 received the annual check in 2012 and 2013. The prevalence of mental illness and the mean score of alcoholism tendency increased during the follow-up period. The majority of respondents (43.8%) with baseline serious mental illness (SMI) continued to have SMI at follow-up; only 16.7% reported recovering. Older age, female sex, and severity of home damage predicted higher psychological distress, while male sex was a risk factor for alcoholism at follow-up. CONCLUSIONS: Psychological distress deteriorated 2 years after the huge natural disaster, compared with 1 year after the disaster. Long-term mental health care is needed for those affected by natural disasters, particularly those who have suffered loss.

Treatment with mild brain hypothermia for cardiopulmonary resuscitation after myoclonic seizures in infant with robertsonian type of trisomy 13.

Congenital chromosomal abnormality with trisomy 13 is known to be associated with poor life prognosis and lethal. Therefore, physician advice the patients be kept in intensive treatment with resuscitation and state of the art intensive care when sudden change in the general condition with this trisomy is observed. We report herein, the treatment with mild brain hypothermia therapy for cardiopulmonary resuscitation after myoclonic seizures in infant with Robertsonian type of trisomy 13 in intensive care unit. Our study indicated that brain hypothermia therapy and steroid pulse therapy on an infant who was believed to have post-resuscitation hypoxic encephalopathy was highly effective as the patient's general condition recovered to the original state after four months.

CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma.

BACKGROUND: Cancer stem cells (CSCs) are responsible for treatment failure. However, their identification and roles in resistance are not well established in head and neck squamous cell carcinoma (HNSCC). METHODS: Three HNSCC cell lines (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell surface antigens were analysed by LyoPlate, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. RESULTS: CD10, CD15s, CD146 and CD282 were upregulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. Isolation mediated by FACS revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. CONCLUSIONS: CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory HNSCC.

The dynamics of herpesvirus reactivations during and after severe drug eruptions: their relation to the clinical phenotype and therapeutic outcome.

BACKGROUND: Drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) represent contrasting poles of severe drug eruptions, and sequential reactivations of several herpesviruses have exclusively been demonstrated in the former. No previous studies, however, were extended beyond the acute stage. We sought to investigate whether herpesvirus reactivations could also be observed in SJS/TEN and beyond the acute stage of both diseases. METHODS: Patients with SJS (n = 16), SJS/TEN overlap (n = 2), TEN (n = 10), and DIHS/DRESS (n = 34) were enrolled. We performed a retrospective analysis of Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and cytomegalovirus (CMV) DNA loads sequentially determined by real-time polymerase chain reaction during a 2-year period after onset. RESULTS: Persistently increased EBV loads were detected in SJS during the acute stage and long after resolution, but not in others. In contrast, high HHV-6 loads were exclusively detected in DIHS/DRESS during the acute stage. The dynamics of herpesvirus reactivation varied in DIHS/DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them. CONCLUSIONS: Distinct patterns of herpesvirus reactivation according to the pathological phenotype and to the use of systemic corticosteroids were observed during the acute stage and follow-up period, which may contribute, at least in part, to the difference in the clinical manifestations and long-term outcomes. Systemic corticosteroids during the acute stage may improve the outcomes in DIHS/DRESS.

Operation status of the electron cyclotron resonance ion source at Gunma University.

An ECR ion source of Gunma University Heavy Ion Medical Center, so-called KeiGM [M. Muramatsu, A. Kitagawa, Y. Sakamoto, S. Sato, Y. Sato, H. Ogawa, S. Yamada, H. Ogawa, Y. Yoshida, and A. G. Drentje, Rev. Sci. Instrum. 76, 113304 (2005)], has been operated for cancer therapy and physical/biological experiment since 2010. KeiGM produces typically 230 µA of 10 keV/u C(4+) ions from CH4 gases. The vacuum pressure is kept between 1.2 × 10(-4) and 1.7 × 10(-4) Pa so as to suppress the pulse-to-pulse current fluctuation within ±10%. The extraction electrode is cleaned every 6-8 months in order to remove deposited carbon, which increases the leak current and discharge. In order to investigate the possibility of long-term operation without such maintenances, oxygen aging for the cleaning of the extraction electrode has been tested in the test bench. The same-designed ion sources at National Institute of Radiological Sciences and SAGA Heavy Ion Medical Accelerator in Tosu (SAGA-HIMAT) are also operated with stable C(4+) current, which are suitable for the continuous operation for cancer therapy.

The continuing debate on deep molluscan phylogeny: evidence for Serialia (Mollusca, Monoplacophora + Polyplacophora).

Molluscs are a diverse animal phylum with a formidable fossil record. Although there is little doubt about the monophyly of the eight extant classes, relationships between these groups are controversial. We analysed a comprehensive multilocus molecular data set for molluscs, the first to include multiple species from all classes, including five monoplacophorans in both extant families. Our analyses of five markers resolve two major clades: the first includes gastropods and bivalves sister to Serialia (monoplacophorans and chitons), and the second comprises scaphopods sister to aplacophorans and cephalopods. Traditional groupings such as Testaria, Aculifera, and Conchifera are rejected by our data with significant Approximately Unbiased (AU) test values. A new molecular clock indicates that molluscs had a terminal Precambrian origin with rapid divergence of all eight extant classes in the Cambrian. The recovery of Serialia as a derived, Late Cambrian clade is potentially in line with the stratigraphic chronology of morphologically heterogeneous early mollusc fossils. Serialia is in conflict with traditional molluscan classifications and recent phylogenomic data. Yet our hypothesis, as others from molecular data, implies frequent molluscan shell and body transformations by heterochronic shifts in development and multiple convergent adaptations, leading to the variable shells and body plans in extant lineages.

Low coseismic friction on the Tohoku-Oki fault determined from temperature measurements.

The frictional resistance on a fault during slip controls earthquake dynamics. Friction dissipates heat during an earthquake; therefore, the fault temperature after an earthquake provides insight into the level of friction. The Japan Trench Fast Drilling Project (Integrated Ocean Drilling Program Expedition 343 and 343T) installed a borehole temperature observatory 16 months after the March 2011 moment magnitude 9.0 Tohoku-Oki earthquake across the fault where slip was ~50 meters near the trench. After 9 months of operation, the complete sensor string was recovered. A 0.31°C temperature anomaly at the plate boundary fault corresponds to 27 megajoules per square meter of dissipated energy during the earthquake. The resulting apparent friction coefficient of 0.08 is considerably smaller than static values for most rocks.

Cenozoic climate change and diversification on the continental shelf and slope: evolution of gastropod diversity in the family Solariellidae (Trochoidea).

Recent expeditions have revealed high levels of biodiversity in the tropical deep-sea, yet little is known about the age or origin of this biodiversity, and large-scale molecular studies are still few in number. In this study, we had access to the largest number of solariellid gastropods ever collected for molecular studies, including many rare and unusual taxa. We used a Bayesian chronogram of these deep-sea gastropods (1) to test the hypothesis that deep-water communities arose onshore, (2) to determine whether Antarctica acted as a source of diversity for deep-water communities elsewhere and (3) to determine how factors like global climate change have affected evolution on the continental slope. We show that although fossil data suggest that solariellid gastropods likely arose in a shallow, tropical environment, interpretation of the molecular data is equivocal with respect to the origin of the group. On the other hand, the molecular data clearly show that Antarctic species sampled represent a recent invasion, rather than a relictual ancestral lineage. We also show that an abrupt period of global warming during the Palaeocene Eocene Thermal Maximum (PETM) leaves no molecular record of change in diversification rate in solariellids and that the group radiated before the PETM. Conversely, there is a substantial, although not significant increase in the rate of diversification of a major clade approximately 33.7 Mya, coinciding with a period of global cooling at the Eocene-Oligocene transition. Increased nutrients made available by contemporaneous changes to erosion, ocean circulation, tectonic events and upwelling may explain increased diversification, suggesting that food availability may have been a factor limiting exploitation of deep-sea habitats. Tectonic events that shaped diversification in reef-associated taxa and deep-water squat lobsters in central Indo-West Pacific were also probably important in the evolution of solariellids during the Oligo-Miocene.

The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism.

OBJECTIVE: Autism appears to have a strong genetic component. The product of the NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene is included in the mitochondrial electron transport chain. METHOD: We performed a case-control study of 235 patients with autism and 214 controls and examined three single-nucleotide polymorphisms (SNPs) within this gene in a Japanese population. We then conducted a transmission disequilibrium test (TDT) analysis in 148 autistic trios. RESULTS: In the case-control study, two SNPs (rs12666974 and rs3779262) showed a significant association with autism (P=0.00064 and 0.00046 respectively). Furthermore, a haplotype containing these two SNPs showed a significant association (P-global=0.0013, individual haplotype A-A: P=0.010). In TDT analysis, the global and A-A haplotype P-values also indicated significant associations. Minor allele and genotype frequencies were decreased in the autistic subjects. CONCLUSION: We found significant association between the NDFA5 gene and autism.