Gastrectomy with or without omentectomy for cT3-4 gastric cancer: a multicentre cohort study.

BACKGROUND: Omentectomy is performed widely for locally advanced gastric cancer to prevent disease recurrence. However, its clinical benefit is unknown. METHODS: This retrospective cohort study compared the outcome of gastrectomy with preservation of the omentum (GPO) and gastrectomy with resection of the omentum (GRO) among patients with cT3-T4 gastric cancer who underwent gastrectomy between 2006 and 2012 in one of five participating institutions. A consensus conference identified 28 variables potentially associated with outcome after gastrectomy for the estimation of propensity scores, and propensity score matching (PSM) was undertaken to control for possible confounders. Postoperative surgical outcomes, overall survival and disease recurrence were compared between GPO and GRO. RESULTS: A total of 1758 patients were identified, of whom 526 remained after PSM, 263 in each group. Median follow-up was 4·9 (i.q.r. 3·1-5·9) years in the GRO group and 5·0 (2·5-6·8) years in the GPO group. The incidence of postoperative complications of Clavien-Dindo grade III or more was significantly higher in the GRO group (17·5 versus 10·3 per cent; P = 0·016). Five-year overall survival rates were 77·1 per cent in the GRO group and 79·4 per cent in the GPO group (P = 0·749). There were no significant differences in recurrence rate or pattern of recurrence between the groups. CONCLUSION: Overall survival and disease recurrence were comparable in patients with cT3-4 gastric cancer who underwent GPO or GRO.

ANTECEDENTES: La omentectomía se realiza ampliamente en el cáncer gástrico localmente avanzado para prevenir la recidiva de la enfermedad. Sin embargo, se desconoce su beneficio clínico. MÉTODOS: Este estudio retrospectivo comparó el resultado de la gastrectomía con preservación del omento (gastrectomy with preservation of the omentum, GPO) con la gastrectomía con resección del omento (gastrectomy with resection of the omentum, GRO) para el cáncer gástrico con estadio clínico T3/T4. Se incluyeron pacientes sometidos a gastrectomía por cáncer gástrico clínico T3/T4 (2006-2012) y se recogieron datos relevantes de 5 hospitales participantes. A través de una conferencia de consenso se identificaron 28 variables potencialmente asociadas con el resultado tras la gastrectomía, mediante las cuales se estimaron las puntuaciones de propensión, utilizándose el emparejamiento por puntuación de propensión (propensity score matching, PSM) para el control de posibles factores de confusión. Los resultados quirúrgicos postoperatorios, la supervivencia global y la recidiva de la enfermedad se compararon entre las gastrectomías con GPO y GRO. RESULTADOS: En total, se identificaron 1.758 pacientes, seleccionándose 526 (263 GRO y 263 GPO) tras el PSM. La mediana (rango intercuartílico) de seguimiento fue de 4,9 años (3,1-5,9) en el grupo GRO y de 5,0 años (2,5-6,8) en el grupo GPO. La incidencia de complicaciones postoperatorias de Clavien-Dindo grado III o más alto fue significativamente más elevada en el grupo GRO que en el grupo GPO (17,1% versus 9,1%; P = 0,010). La supervivencia global a los 5 años fue del 77,1% para el grupo GRO y del 79,4% para el grupo GPO (P = 0,749). No hubo diferencias estadísticamente significativas en la tasa de recidiva o patrón de recidiva entre ambos grupos. CONCLUSIÓN: La supervivencia global y la recidiva de la enfermedad son comparables en pacientes con cáncer gástrico estadio clínico T3-4 sometidos a GPO o GRO.

Thermo-, photo-, and mechano-responsive liquid crystal networks enable tunable photonic crystals.

Tunable photonic crystals exhibiting optical properties that respond reversibly to external stimuli have been developed using liquid crystal networks (LCNs) and liquid crystal elastomers (LCEs). These tunable photonic crystals possess an inverse opal structure and are photo-responsive, but circumvent the usual requirement to contain dye molecules in the structure that often limit their applicability and cause optical degradation. Herein, we report tunable photonic crystal films that reversibly tune the reflection peak wavelength under thermo-, photo- and mechano-stimuli, through bilayering a stimuli-responsive LCN including azobenzene units with a colourless inverse opal film composed of non-responsive, flexible durable polymers. By mechanically deforming the azobenzene containing LCN via various stimuli, the reflection peak wavelength from the bilayered film assembly could be shifted on demand. We confirm that the reflection peak shift occurs due to the deformation of the stimuli-responsive layer propagating towards and into the inverse opal layer to change its shape in response, and this shift behaviour is repeatable without optical degradation.

Zinc-substituted hydroxyapatite: a biomaterial with enhanced bioactivity and antibacterial properties.

Hydroxyapatite (HA) is a synthetic biomaterial and has been found to promote new bone formation when implanted in a bone defect site. However, its use is often limited due to its slow osteointegration rate and low antibacterial activity, particularly where HA has to be used for long term biomedical applications. This work will describe the synthesis and detailed characterization of zinc-substituted HA (ZnHA) as an alternative biomaterial to HA. ZnHA containing 1.6 wt% Zn was synthesized via a co-precipitation reaction between calcium hydroxide, orthophosphoric acid and zinc nitrate hexahydrate. Single-phase ZnHA particles with a rod-like morphology measuring ~50 nm in length and ~15 nm in width, were obtained and characterized using transmission electron microscopy and X-ray diffraction. The substitution of Zn into HA resulted in a decrease in both the a- and c-axes of the unit cell parameters, thereby causing the HA crystal structure to alter. In vitro cell culture work showed that ZnHA possessed enhanced bioactivity since an increase in the growth of human adipose-derived mesenchymal stem cells along with the bone cell differentiation markers, were observed. In addition, antibacterial work demonstrated that ZnHA exhibited antimicrobial capability since there was a significant decrease in the number of viable Staphylococcus aureus bacteria after in contact with ZnHA.

CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1.

We have identified a novel gene containing CAG repeats and mapped it to chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD). In normal individuals the gene contains between 13 and 36 CAG repeats, whereas most of the clinically diagnosed patients and all of the affected members of a family with the clinical and pathological diagnosis of MJD show expansion of the repeat-number (from 68-79). Southern blot analyses and genomic cloning demonstrates the existence of related genes. These results raise the possibility that similar abnormalities in related genes may give rise to diseases similar to MJD.

Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.

BACKGROUND: In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in patients with advanced renal cell carcinoma across all International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor); analyses of overall survival (OS) remain immature. Here, we report post hoc analyses of efficacy from the third interim analysis (data cut-off, April 2020) by the numbers of IMDC risk factors and target tumor sites at baseline. METHODS: Efficacy endpoints assessed were PFS, objective response, and best overall response per investigator assessment (RECIST v1.1) and OS. Best percentage change and percentage change from baseline in target tumor size over time during the study were also assessed. RESULTS: In patients with 0, 1, 2, 3, or 4-6 IMDC risk factors, hazard ratios [HRs; 95% confidence interval (CIs)] for OS with avelumab + axitinib versus sunitinib were 0.660 (0.356-1.223), 0.745 (0.524-1.059), 0.973 (0.668-1.417), 0.718 (0.414-1.248), and 0.443 (0.237-0.829), and HRs (95% CIs) for PFS were 0.706 (0.490-1.016), 0.709 (0.540-0.933), 0.711 (0.527-0.960), 0.501 (0.293-0.854), and 0.395 (0.214-0.727), respectively. In patients with 1, 2, 3, or ≥4 target tumor sites, HRs (95% CIs) for OS with avelumab + axitinib versus sunitinib were 0.912 (0.640-1.299), 0.715 (0.507-1.006), 0.679 (0.442-1.044), and 0.747 (0.346-1.615), and HRs (95% CIs) for PFS were 0.706 (0.548-0.911), 0.552 (0.422-0.723), 0.856 (0.589-1.244), and 0.662 (0.329-1.332), respectively. Across all subgroups, analyses of objective response rate and complete response rate favored avelumab + axitinib versus sunitinib, and a greater proportion of patients treated with avelumab + axitinib had tumor shrinkage. CONCLUSIONS: In post hoc analyses, first-line treatment with avelumab + axitinib was generally associated with efficacy benefits versus treatment with sunitinib in patients with advanced renal cell carcinoma across subgroups defined by different numbers of IMDC risk factors or target tumor sites.

Relationship between the combination of polyunsaturated fatty acids intake and psychological distress during pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

No studies have examined the association of the combination of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs intake with psychological distress during pregnancy. To examine these associations, we divided Japanese pregnant women into 25 groups based on combining quintiles of n-3 PUFAs intake and quintiles of n-6 PUFAs intake. We conducted multivariable logistic regression analyses to assess the risk of psychological distress during pregnancy (Kessler Psychological Distress Scale ≥ 5 or 13). Compared to the third quintile of both n-3 PUFAs and n-6 PUFAs intake, the groups with unbalanced intake, high intake of both, and low intake of both were associated with a higher risk of both Kessler Psychological Distress Scale ≥ 5 and 13 in early and mid-pregnancy. Further research is needed to identify the precise combination of n-3 PUFAs and n-6 PUFAs intake associated with the lowest psychological distress during pregnancy.

Electrically induced NGF production by astroglial cells.

A controlled culture system has been developed to induce nerve growth factor (NGF) production in astroglial cells that are cultured on an electrode surface. The electrode potential is alternatively modulated at an amplitude of 300 mV and a frequency of 10 Hz. The electric stimulation triggers NGF production and secretion. The mechanism of the electrically induced NGF production is discussed in association with protein kinase C (PKC) activation.

Analysis of feeding behavior with direct linear transformation.

AIM: The sucking pattern of term infants is composed of a rhythmic alteration of expression and suction movements. The aim is to evaluate if direct linear transformation (DLT) method could be used for the assessment of infant feeding. SUBJECT AND METHODS: A total of 10 gnormalh infants and two infants with neurological disorders were studied using DLT procedures and expression/suction pressure recordings. Feeding pattern of seven gnormalh infants were evaluated simultaneously recording DLT and pressures. The other infants were tested non-simultaneously. We placed markers on the lateral angle of the eye, tip of the jaw, and throat. The faces of infants while sucking were recorded in profile. The jaw and throat movements were calculated using the DLT procedure. Regression analysis was implemented to investigate the relationship between suction and expression pressures and eye-jaw and eye-throat movement. All regression analyses investigated univariate relationships and adjusted for other covariates. RESULTS: Ten gnormalh infants demonstrated higher suction pressure than expression pressure, and their throat movements were larger than jaw movements. Two infants with neurological problems did not generate suction pressure and demonstrated larger movements in their jaw than throat. The simultaneous measurement (n=7) showed a significant correlation, not only between eye-jaw distance and the expression pressure, but also between eye-throat distance and suction pressure. The change in the eye-jaw distance was smaller than the changes in the eye-throat distance in gnormalh infants (p<0.001). CONCLUSIONS: The DLT method can be used to evaluate feeding performance without any special device.

Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity.

Tumor-infiltrating lymphocytes, particularly CD8(+) T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8(+) but also CD4(+) T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8(+) T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8(+) T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.

Electrochemical regeneration of nicotinamide adenine dinucleotide.

Reduced nicotinamide adenine dinucleotide (NADH) has been characterized electrochemically by solid electrode voltammetry and controlled potential electrolysis. Photometric and enzymatic assay showed that enzymatically active nicotinamide adenine dinucleotide (NAD-+) could be regenerated electrolytically from its reduced form without the use of so-called electron mediators. Complete regeneration of enzymatically active NAD can be expected in pyrophosphate buffers and phosphate buffers during the electrolysis. Advantages of electrochemical regeneration of coenzymes are discussed, especially with regard to immobilization of enzymes.

Electrochemical characterization of immobilized NAD+.

Nicotinamide adenine dinucleotide (NAD+) has been covalently attached to alginic acid using carbodiimide coupling, thereby producing a macromolecular adduct of NAD, which can be rendered either soluble or insoluble by adjustment of pH. It was found that this NAD+-alginic acid complex was enzymatically active, and also that the oxidized form could be electrochemically reduced without loss in enzymatic activity. This NAD+ adduct has now also been polarographically characterized as to its two-step reduction waves, which are slightly shifted toward more cathodic potential as compared to free NAD+. When controlled electrolysis was conducted to reduce the bound NAD+ at the cathode, the NADH so formed by electrochemical action was found to be again oxidizable either enzymatically or electrochemically without loss in co-enzymatic function. The NADH adduct produced by electrochemical reduction of the NAD+ adduct has also been characterized by voltammetry.

Antibacterial polyetheretherketone implants immobilized with silver ions based on chelate-bonding ability of inositol phosphate: processing, material characterization, cytotoxicity, and antibacterial properties.

We developed a novel antibacterial implant by forming a hydroxyapatite (HAp) film on polyetheretherketone (PEEK) substrate, and then immobilizing silver ions (Ag(+) ) on the HAp film based on the chelate-bonding ability of inositol phosphate (IP6). First, the PEEK surface was modified by immersion into concentrated sulfuric acid for 10 min. HAp film was formed on the acid-treated PEEK via the soft-solution process using simulated body fluid (SBF), urea, and urease. After HAp coating, specimens were immersed into IP6 solution, and followed by immersion into silver nitrite solution at concentrations of 0, 0.5, 1, 5 or 10 mM. Ag(+) ions were immobilized on the resulting HAp film due to the chelate-bonding ability of IP6. On cell-culture tests under indirect conditions by Transwell, MC3T3-E1 cells on the specimens derived from the 0.5 and 1 mM Ag(+) solutions showed high relative growth when compared with controls. Furthermore, on evaluation of antibacterial activity in halo test, elution of Ag(+) ions from Ag(+) -immobilized HAp film inhibited bacterial growth. Therefore, the above-mentioned results demonstrated that specimens had both biocompatibility and strong antibacterial activity. The present coating therefore provides bone bonding ability to the implant surface and prevents the formation of biofilms in the early postoperative period.

Characterization of quinolone antibacterial-induced convulsions and increases in nuclear AP-1 DNA- and CRE-binding activities in mouse brain.

The quinolone antibacterials enoxacin and norfloxacin (2.5 mg/kg, i.v.) provoked clonic convulsions in mice treated concomitantly with biphenylacetic acid (BPAA, 100 mg/kg, i.p.), a major metabolite of the nonsteroidal anti-inflammatory drug fenbufen. Gel-shift assays showed that enoxacin-induced convulsions resulted in increases in nuclear activator protein 1 (AP-1) DNA- and cyclic AMP responsive element (CRE)-binding activities in the cerebral cortex and hippocampus, but not in other regions, such as the cerebellum and thalamus. In contrast, ofloxacin and levofloxacin, at the same doses, in the presence of BPAA did not evoke convulsions or increase these DNA-binding activities. Administration of these quinolones and BPAA alone elicited neither convulsions nor increases in these DNA-binding activities. These results suggest that the increased nuclear AP-1 DNA- and CRE-binding activities in the cerebral cortex and hippocampus induced by quinolones with BPAA correlated with seizure activities and that these brain regions play pivotal roles in quinolone-induced convulsions.

gamma-Butyrolactone-induced absence-like seizures increase nuclear CRE- and AP-1 DNA-binding activities in mouse brain.

We examined the involvement of the GABAB receptor and the coordinated induction of nuclear transcriptional factors in experimental generalized absence seizures induced by gamma-butyrolactone (GBL) in mice. Although administration of GBL 50 mg/kg did not show any effects on behavior or ECoG pattern, higher doses of GBL (70 and 100 mg/kg, i.p.) induced behavioral changes associated with 3-6-Hz spike and wave discharges in the mice. CGP 35348, a GABAB receptor antagonist, suppressed both the GBL-induced absence seizures and the spike and wave discharges. The antiepileptic effects of CGP 35348 (200 mg/kg, i.p.) were stronger than those of ethosuximide (200 mg/kg, i.p.). Sodium valproate (100 mg/kg, i.p.) attenuated the early phase but not the late phase of the GBL-induced absence seizures. Gel-mobility assay demonstrated that administration of an effective dose of GBL for eliciting spike and wave discharges dose-dependently increased nuclear cyclic AMP-responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in mouse whole brain. The increases in nuclear CRE- and AP-1 DNA-binding were antagonized by CGP 35348 in a dose-dependent fashion. In addition, GABAB receptor binding assay revealed that GBL or antiepileptic drugs did not displace [3H]baclofen binding in cerebral cortical membranes. In contrast, gamma-hydroxybutyrate (GHB), an active metabolite of GBL, inhibited [3H]baclofen binding in a concentration-dependent manner. These results suggest that GABAB receptor-mediated synaptic responses are involved in GBL-induced generalized absence seizures and that the increases in nuclear CRE- and AP-1 DNA-binding activities are correlated with the GBL-induced generalized absence seizures.

Differential expression of HLA-class II antigens in the human thymus. Relative paucity of HLA-DQ antigens in the thymic medulla.

By using well-characterized monoclonal antibodies, HU-20, HOK7(1E4) and HU-18, which specifically recognize either common epitopes of HLA-DR molecules (HU-20, HOK7) or HLA-DQw3 molecules (HU-18), it was demonstrated that there were different distributions of these antigens in human thymus. In the cortex, both DR and DQ antigens were strongly expressed on thymic epithelial cells (TEC). The double stainings revealed simultaneous expression of both antigens on TEC. On the other hand, in the medulla, DQ antigens had more limited expression than DR antigens, the latter antigens being demonstrated in the confluent pattern. The double staining method could show small numbers of dual-positive cells in the medulla, which looked like TEC, indicating that at least some medullary TEC were also DR+,DQ+, although the presence of small numbers of DR-,DQ-, as well as DR+,DQ- TEC in the medulla cannot be excluded. The preponderance of DR over DQ antigen in the medulla was consistently found--from a ten week embryo to a two-year-old child--and could be attributed to very weak or no expression of DQ antigens on dendritic cells/macrophages. The distribution pattern of these antigens within the thymus may have correlations with the intrathymic development of T cells through the unique functions of each antigen.

Leukocyte subsets infiltrating into fully allogeneic, long-surviving rat liver allografts.

Leukocyte subsets that infiltrated into unmodified LEJ(RT1j)2 liver grafts from WKAH(RT1k) hosts were studied. This strain combination is fully allogeneic and yields acute rejections in skin and kidney transplantations. On days 3, 7, and 14, cellular infiltrates gradually increased, and many hepatocytes were degenerative and lost cellular glycogen. Blastoid lymphocytes were frequently seen, and mitotic features of hepatocytes were prominent (on day 14, 3 to 4/10 high-power fields). Later, on days 30, 50, and 300, the cellular infiltrates gradually subsided, and blastoid lymphocytes were rarely seen. Throughout the course, Ia+ cells (RT1.Dk+ and/or RT1.B+ cells) were the major cell populations infiltrating into the grafts. Most of the host RT1.D+ cells were histiocytoid in appearance on immunoelectron microscopy. Histiocytoid cells were the most numerous infiltrating cells, constituting 30-50% of the total infiltrating cells. There were different distributions of T cell subsets between the portal and sinusoidal areas, as we previously observed in acutely rejected rat renal allografts. Both RLyt-1+,2-(Th) and RLyt-1+,2+(Tc/s) cells were found almost equally in the portal area, while RLyt-1+,2+(Tc/s) cells predominated over RLyt-1+,2-(Th) cells in the sinusoidal area. However, a gradual replacement of RLyt-1+,2-(Th) cells by RLyt-1+,2+(Tc/s) cells, as seen in the perivascular area of renal grafts, was not found in the portal areas of the liver grafts. Except for the latter finding, the pattern of cellular infiltrates was similar to that of acute renal rejection, and the significance of these cellular infiltrates is discussed.

HLA-linked susceptibility gene of Takayasu Disease.

The HLA-A, B, DR and MB antigens were investigated in patients suffering from Takayasu disease (Aortitis syndrome). Out of twenty-one HLA-A and B antigens tested, only HLA-Bw52 was significantly deviated (30147, PF = 63.8%, RR = 7.8) from the controls (14/76, PF = 18.4%). Since in the Japanese, HLA-Bw52 is in positive linkage disequilibria with HLA-DR2 and MB1, the association of the DR2 and MB1 antigens with Takayasu disease was studied. The HLA-DR2 antigen was significantly increased (23/30, PF = 76.7%,, RR = 6.0) in patients compared with the control (18/51, PF = 35.3%). Moreover, an almost perfect association of MBI (29/30, PF = 96.7%, RR = 12.6) with Takayasu disease was demonstrated. This finding supports the hypothesis that the genes in the HLA-D region play a major role in determining the susceptibility to Takayasu disease.

Association of B cell alloantigen with juvenile onset diabetes mellitus in the Japanese.

Sixty-four Japanese insulin dependent juvenile onset diabetes mellitus (JOD) were studied in relation to HLA-A, B, and DR. Significant deviations were observed. HLA-Bw54 was increased (PF = 49.2%, RR = 6.4) and HLA-B5 was decreased (PF = 7.9%, RR = 0.19). Using radioimmunoassay, two HLA-DR antigens were investigated. Hon 7 antigen, so-called MT3 (WIA4x7), which has linkage disequilibrium between HLA-BW54, is highly associated (PF = 96.9%, RR = 27.8) with JOD found in the Japanese.

Association between the MB system and asthma in the Japanese.

Twenty-three unrelated Japanese patients with asthma who showed a high total serum IgE level, a strong skin test response to Dermatophagoides farinae, and a high score on a radioallergosorbent test (RAST) using Dermatophagoides farinae were typed for HLA-A locus, -B locus, and -D region antigens. No significant difference in the frequencies of HLA-A, -B, and -DR antigens were observed between the asthma patients and the healthy controls. A significant difference in the frequency of MB3', however, was found between the asthma patients and the healthy controls (corrected p = 0.04, relative risk = 18.5).

A study on class II antigens involved in the T cell proliferative responses to PPD using cross-reacting monoclonal antibodies in human and murine system.

Two monoclonal antibodies (MoAb) 1E4 and ISCR3, which detect class II antigens across species barriers, were studied for their inhibitory effects on human and murine T cell proliferative responses to purified protein derivative of tuberculin (PPD). The 1E4 detected at least a polymorphic determinant on I-A molecules from mice carrying the H-2b haplotype, and the ISCR3 detected the Ia.7 determinant on I-E molecules. Nevertheless, both 1E4 and ISCR3 recognized monomorphic determinants on HLA-DR antigens (human I-E equivalent molecules), but not on HLA-DQ antigens (human I-A equivalent molecules). It was demonstrated that 1E4 significantly inhibited PPD-specific responses of T cells from Ib-bearing mice. In contrast, ISCR3 showed marginal effects on the responses of mice bearing Ia.7. However, in the human system both 1E4 and ISCR3 reduced proliferative responses to PPD. These results suggest that a functional difference exists between humans and mice in the I subregion products involved in the T cell proliferative responses to PPD.