X-Ray Magnetic Circular Dichroism in Altermagnetic α-MnTe.

Altermagnetism is a recently identified magnetic symmetry class combining characteristics of conventional collinear ferromagnets and antiferromagnets, that were regarded as mutually exclusive, and enabling phenomena and functionalities unparalleled in either of the two traditional elementary magnetic classes. In this work we use symmetry, ab initio theory, and experiments to explore x-ray magnetic circular dichroism (XMCD) in the altermagnetic class. As a representative material for our XMCD study we choose α-MnTe with compensated antiparallel magnetic order in which an anomalous Hall effect has been already demonstrated. We predict and experimentally confirm a characteristic XMCD line shape for compensated moments lying in a plane perpendicular to the light propagation vector. Our results highlight the distinct phenomenology in altermagnets of this time-reversal symmetry breaking response, and its potential utility for element-specific spectroscopy and microscopy.

Standardization of preoperative stoma site marking and its utility for preventing stoma leakage: a retrospective study of 519 patients who underwent laparoscopic/robotic rectal cancer surgery.

PURPOSE: Stoma site marking is an important preoperative intervention for preventing various stoma-associated complications. In our institution, standardized stoma site marking is routinely performed before rectal cancer surgery with stoma creation, and various stoma-associated factors are recorded in the ostomy-record template. The present study investigated risk factors for stoma leakage. METHODS: Our stoma site marking is standardized so that it can be performed by non-stoma specialists. To identify risk factors of stoma leakage at 3 months after surgery, various preoperative factors associated with stoma site marking in our ostomy-record template were retrospectively analyzed in 519 patients who underwent rectal cancer surgery with stoma creation from 2015 to 2020. RESULTS: Stoma leakage was seen in 35 of the 519 patients (6.7%). The distance between the stoma site marking and the umbilicus was less than 60 mm in 27 of the 35 patients (77%) who experienced stoma leakage, so a distance of less than 60 mm was identified as an independent risk factor for stoma leakage. Aside from preoperative factors, stoma leakage was also caused by postoperative skin wrinkles or surgical scars near the stoma site in 8 of 35 patients (23%). CONCLUSION: Preoperative standardized stoma site marking is necessary to achieve reliable marking that is easy to perform. To reduce the risk of stoma leakage, a distance of 60 mm or more between the stoma site marking and the umbilicus is ideal, and surgeons need to contrive ways to keep surgical scars away from the stoma site.

First Application of Mass Measurements with the Rare-RI Ring Reveals the Solar r-Process Abundance Trend at A=122 and A=123.

The Rare-RI Ring (R3) is a recently commissioned cyclotronlike storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF-^{127}Sn, ^{126}In, ^{125}Cd, ^{124}Ag, ^{123}Pd-were injected in R3. Masses of ^{126}In, ^{125}Cd, and ^{123}Pd were measured whereby the mass uncertainty of ^{123}Pd was improved. This is the first reported measurement with a new storage ring mass spectrometry technique realized at a heavy-ion cyclotron and employing individual injection of the preidentified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new ^{123}Pd result on the solar r-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction Y_{e}. It is found that the neutron capture cross section on ^{123}Pd increases by a factor of 2.2 and ß-delayed neutron emission probability, P_{1 n}, of ^{123}Rh increases by 14%. The neutron capture cross section on ^{122}Pd decreases by a factor of 2.6 leading to pileup of material at A=122, thus reproducing the trend of the solar r-process abundances. The trend of the two-neutron separation energies (S_{2n}) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S_{2n} value at N=77. Such large increase of the S_{2n} values before N=82 was proposed as an alternative to the quenching of the N=82 shell gap to reproduce r-process abundances in the mass region of A=112-124.

WHO informal consultation on revision of guidelines on evaluation of similar biotherapeutic products, virtual meeting, 30 June - 2 July 2021.

The WHO informal consultation was held to promote the revision of WHO guidelines on evaluation of similar biotherapeutic products (SBPs) adopted by the Expert Committee on Biological Standardization (ECBS) in 2009. It was agreed in the past consultations that the evaluation principles in the guidelines are still valid, but a review was recommended to provide more clarity and case-by-case flexibility. The opportunity was therefore taken to review the experience and identify areas where the current guidance could be more permissive without compromising its basic principles, and where additional explanation could be provided regarding the possibility of reducing the amount of data needed for regulatory approval. The meeting participants applauded the leading role taken by the WHO in providing a much-needed streamlined approach for development and evaluation of SBPs which will provide efficient and cost-effective product development and increase patient access to treatments. It was recognized that the principles as currently described in the draft WHO guidelines are based on sound science and experience gained over the last fifteen years of biosimilar approvals. However, since these guidelines when finalised will constitute the global standard for biosimilar evaluation and assist national regulatory authorities in establishing revised guidance and regulatory practice in this complex area, it was felt that further revision and clarity on certain perspectives in specific areas was necessary to dispel uncertainties arising in the current revised version. This report describes the principles in the draft guidelines, including topics discussed and consensus reached.

Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study.

Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication. INTRODUCTION: This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent. METHODS: Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not. CONCLUSIONS: These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.

The structure of aqueous solutions of hexafluoro-iso-propanol studied by neutron diffraction with hydrogen/deuterium isotope substitution and empirical potential structure refinement modeling.

Neutron diffraction measurements of H/D isotopic substitution are made at room temperature for seven H/D substituted hexafluoro-iso-propanol (HFIP; 1,1,1,3,3,3-hexafluoro-2-propanol)-water mixtures at 0.1, 0.2, and 0.4 HFIP mole fraction (xHFIP). The eight partial structure factors except for the H(CH)-H(CH) pair obtained are subjected to an empirical potential structure refinement (EPSR) method to derive all site-site pair correlation functions. It is found that with increasing HFIP concentration the ice-like network of water disappears between xHFIP = 0.1 and 0.2, followed by the formation of a chain-like water structure embedded in an intrinsic structure of HFIP evolved at xHFIP = 0.4. The hydroxyl group of HFIP forms hydrogen bonds with the surrounding water molecules at all HFIP mole fractions investigated. There is no evidence that the water structure is well defined around the CF3 groups of HFIP, but water molecules surround tangentially the CF3 groups of HFIP.

Long-term follow-up of the randomized trial of mesorectal excision with or without lateral lymph node dissection in rectal cancer (JCOG0212).

BACKGROUND: Japan Clinical Oncology Group (JCOG) 0212 (ClinicalTrials.gov NCT00190541) was a non-inferiority phase III trial of patients with clinical stage II-III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence-free survival (RFS). The planned primary analysis at 5 years failed to confirm the non-inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long-term follow-up data from JCOG0212. METHODS: Patients with clinical stage II-III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. RESULTS: A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7-year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non-inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). CONCLUSION: Long-term follow-up data did not support the non-inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.

ANTECEDENTES: El JCOG0212 (ClinicalTrials.gov: NCT00190541) fue un ensayo fase III de no inferioridad en pacientes con cáncer de recto en estadio clínico II/III sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. El ensayo comparó la escisión del mesorrecto (mesorectal excision, ME) con la ME con disección de los ganglios linfáticos laterales (lateral lymph node dissection, LLND), siendo el criterio de valoración principal la supervivencia libre de recidiva (recurrence free survival, RFS). El análisis primario planificado a los 5 años de seguimiento no pudo confirmar la no inferioridad de la ME frente a la ME con LLND. Este estudio tuvo como objetivo comparar la ME como procedimiento único y la ME con LLND utilizando datos de seguimiento a largo plazo del ensayo JCOG0212. MÉTODOS: En este estudio se incluyeron pacientes con cáncer de recto en estadio clínico II/III por debajo de la reflexión peritoneal sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. Después de que los cirujanos confirmaran la resección R0 mediante la ME, los pacientes fueron asignados al azar al brazo de ME sola o al brazo de ME con LLND. El criterio de valoración principal fue la supervivencia libre de recidiva (RFS). RESULTADOS: Un total de 701 pacientes de 33 instituciones fueron asignados al azar para ser tratados mediante una ME con LLND (n = 351) o EM sola (n = 350) entre junio de 2003 y agosto de 2010. Las tasas de RFS a 7 años fueron del 71,1% para ME con LLND y 70,7 % para ME sola (cociente de riesgos instantáneos, hazard ratio, HR: 1,09 (i.c. del 95% 0,84-1,42), no inferioridad P = 0,064)). El análisis de subgrupos mostró una mejor RFS entre los pacientes en estadio clínico III que se sometieron a ME con LLND en comparación con ME sola (HR: 1,49 (i.c. del 95%: 1,02-2,17)). CONCLUSIÓN: Los datos de seguimiento a largo plazo no justificaron la no inferioridad de la ME en comparación con la ME con LLND. Se recomienda la ME con LLND para pacientes en estadio clínico III, mientras que LLND podría omitirse para pacientes en estadio clínico II.

Photodissociation spectroscopy of N2O+ in the ion storage ring RICE.

The A2Σ+-X2Π electronic transition of the nitrous oxide cation, N2O+, was measured via photodissociation spectroscopy in a cryogenic electrostatic ion storage ring. Rotationally resolved spectra of the N-O stretching vibrational sequence were obtained by detecting neutral N fragments produced via N2O+ → NO+ + N predissociation channels. A new set of molecular constants was determined for the high-lying vibrational levels of the A2Σ+ state.

Bilirubin oxidation derived from oxidative stress is associated with disease severity of atopic dermatitis in adults.

BACKGROUND: Bilirubin is an essential antioxidant. Its oxidative metabolites, biopyrrins, are sensitive urinary markers of oxidative stress. Multiple studies suggest that oxidative stress affects the pathogenesis of skin diseases such as atopic dermatitis (AD). AIM: To examine oxidative stress-induced bilirubin oxidation and its association with AD pathogenesis in adults. METHODS: In total, 11 patients with AD and 7 healthy controls (HCs) were enrolled. Bilirubin oxidation profiles in the combined urine of the patients and that of the HCs were examined using high-performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry. The concentrations of urinary biopyrrins and serum biomarkers for AD disease severity, such as IgE and thymus and activation-regulated chemokine (TARC)/CCL17, were measured by ELISA to determine correlations between urinary biopyrrins and serum biomarkers. Local bilirubin oxidation in AD skin lesions was assessed by immunohistochemical analyses using two antibodies against bilirubin. RESULTS: Levels of dipyrrole-monopyrrole-aldehyde, a novel urinary biopyrrin, were higher in patients with AD than in HCs, and increased with disease severity based on the SCORing Atopic Dermatitis (SCORAD) objective scoring system. Additionally, urinary biopyrrin levels correlated significantly with serum IgE and TARC/CCL17 levels. Furthermore, immunohistochemical analyses revealed that biopyrrins were strongly expressed in both infiltrating and resident cells in AD lesions. However, bilirubin was expressed at low levels in the lesions, suggesting that bilirubin oxidation is augmented in AD lesions. CONCLUSIONS: Bilirubin oxidation derived from oxidative stress in the skin lesions can be associated with disease severity of AD.

S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase III, noninferiority trial.

Background: Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS). Patients and methods: Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin. Result: Between June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6-11.6) in the control group and 14.0 months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P < 0.0001 for noninferiority, P = 0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher. Conclusion: S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment. Clinical trials number: UMIN000007834.

Subpopulation Primers Essential for Exhaustive Detection of Diverse Hemagglutinin Genes of H5 Subtype Avian Influenza Viruses by Loop-Mediated Isothermal Amplification Method.

Loop-mediated isothermal amplification (LAMP) is a potential screening test for avian influenza (AI), but its narrow detection spectrum limits its applications. To improve this narrow detection spectrum, 3 types of primers were compared for detection of diverse H5 subtype hemagglutinin (HA) genes. Four and 6 genes, of 10 genetically different H5 HA genes tested, were detected with S primers specific for A/duck/Tsukuba/9/2005 (H5N2) and with M primers (which contained mixed bases), respectively. In contrast, all 10 HA genes became positive with population primers (P primers) (a mixture of primers designed for each subpopulation of 2,202 HA genes). Our study indicated that the P primers for the forward inner primer (FIP) and backward inner primer (BIP) sites were essential for exhaustive detection, whereas those for the F3, forward loop (FL), backward loop (BL), and B3 sites were exchangeable with M primers. A base mismatch experiment demonstrated that HA genes with ≤2 base mismatches per primer site and ≤10 base mismatches per HA gene were amplifiable. Reverse transcription-LAMP was broadly reactive, specific for H5 subtype HA genes, and applicable to field samples, with the sensitivity of real-time PCR. The in silico analysis suggested that most H5 HA genes (2,586 positive genes/2,588 genes tested) registered in the GenBank database might be amplifiable. These results indicate that the use of subpopulation primers in LAMP allows exhaustive detection of diverse HA genes and H5 LAMP can be used as a reliable AI screening test in general diagnostic laboratories.

Thermal behavior, structure, dynamic properties of aqueous glycine solutions confined in mesoporous silica MCM-41 investigated by x-ray diffraction and quasi-elastic neutron scattering.

Differential scanning calorimetry, X-ray diffraction, and quasi-elastic neutron scattering (QENS) measurements of aqueous glycine solutions confined in mesoporous silica (MCM-41) were performed at different glycine concentrations, pH, and loading ratio (=mass of glycine solution/mass of dry MCM-41) in the temperature range from 305 to 180 K to discuss the confinement effect on the thermal behavior, the structure, and the dynamic properties of the solutions. The freezing points of the confined glycine solutions decreased, compared with those of the bulk solutions. The corresponding exothermic peak due to ice formation became broader with an increase in the glycine concentration. By subtracting X-ray diffraction patterns of dry MCM-41 from those of glycine solution-loaded MCM-41, information about the structure of the confined glycine solutions was obtained. The radial distribution functions of the confined glycine solutions showed that the peaks assigned to the interaction between glycine molecules and the surface silanol (Si-OH) groups of MCM-41 at pH = 5 were observed, in contrast to the case at pH = 2. The QENS data on H/D substituted aqueous glycine solutions gave the translational diffusion coefficients and the residence time of glycine and water molecules confined in MCM-41 individually. The activation energy of the diffusion coefficient of a glycine molecule at pH = 5 was larger than that at pH = 2. These results imply that glycine molecules locate near the pore surface of MCM-41 due to the formation of hydrogen bonding between glycine molecules and the silanol group of the MCM-41 wall at pH = 5.

SurePath® LBC improves the diagnostic accuracy of intrahepatic and hilar cholangiocarcinoma.

INTRODUCTION: The current study aimed to compare cytology using SurePath® (SP)-LBC and biliary tissue histology (BTH) for the diagnosis of biliary disease. METHODS: Between January 2014 and December 2016, 57 patients underwent endoscopic retrograde cholangiopancreatography for the diagnosis of biliary disease. Biliary cytological samples were processed using SP-LBC and subsequently BTH was performed. A final diagnosis was confirmed by surgery (23 malignant cases) and clinical follow-up (34 benign and malignant cases): 18 extrahepatic cholangiocarcinoma; 17 intrahepatic/hilar cholangiocarcinoma (intra/H-CC); eight other malignant disease; and 14 benign biliary disease. The diagnoses made using SP-LBC and BTH were classified into four categories: (1) benign; (2) indeterminate; (3) suspicious for malignancy/malignant; and (4) inadequate. In addition, diagnostic accuracy was compared between SP-LBC and BTH. RESULTS: Although 23% (13/57) of BTH samples were classified as inadequate, all SP-LBC cases were classified as adequate. Among 43 malignant cases, 11 normal, four indeterminate and 28 suspicious for malignancy/malignant were found using SP-LBC (26%, 9% and 65%, respectively), in contrast to 10 inadequate, nine normal, 10 indeterminate and 14 suspicious for malignancy/malignant observed using BTH (23%, 21%, 23%, and 33%, respectively). The identification of malignant cells was strikingly different between SP-LBC and BTH. Furthermore, limited to intra/H-CC, accuracy was significantly higher using SP-LBC than using BTH (P < .001). CONCLUSIONS: SP-LBC of the biliary tract is a useful and reliable method for diagnosing biliary malignant disease and has an advantage over BTH for detecting malignant cells and accurately diagnosing intra/H-CC.

SHORT CHAIN FATTY ACIDS UPREGULATE ADIPOKINE PRODUCTION IN TYPE 2 DIABETES-DERIVED HUMAN ADIPOCYTES.

PURPOSE: Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. MATERIALS AND METHODS: Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. RESULTS: In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). CONCLUSION: SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.

Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.

Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.

Role of Prealbumin as a Powerful and Simple Index for Predicting Postoperative Complications After Gastric Cancer Surgery.

BACKGROUND: Preoperative factors, including nutritional status, may have strong correlations with postoperative morbidities. The current study evaluated preoperative prealbumin concentrations as a predictor of postoperative complications after gastric surgery. METHODS: A retrospective study of 1798 patients who underwent gastrectomy for gastric adenocarcinoma was performed. Information was collected on basic patient characteristics, preoperative laboratory findings, and 30 day postoperative complications. The patients were divided into three groups based on prealbumin concentrations (≥22 mg/dL, <22 to ≥15 mg/dL, and <15 mg/dL) for analysis. RESULTS: The overall complication rate was 21.7 %, and the infection rate was 16 %. Subgroup analysis based on prealbumin concentrations showed that complication rates were markedly elevated with decreasing concentrations of prealbumin. Multivariate analysis using a logistic regression model showed that both overall and infectious complications were strongly associated with male gender, elevated C-reactive protein (CRP), and decreased prealbumin levels (p < 0.05). Even in patients with a CRP level higher than 0.1 mg/dL, male gender and low prealbumin concentrations (<15 mg/dL) were significantly correlated with overall and infectious morbidities (p < 0.05). CONCLUSIONS: Preoperative prealbumin concentrations are useful predictors of short-term postoperative outcomes after gastrectomy.

Control of tunnel barriers in multi-wall carbon nanotubes using focused ion beam irradiation.

We have formed tunnel barriers in individual multi-wall carbon nanotubes using the Ga focused ion beam irradiation. The barrier height was estimated by the temperature dependence of the current (Arrhenius plot) and the current-voltage curves (Fowler-Nordheim plot). It is shown that the barrier height has a strong correlation with the barrier resistance that is controlled by the dose. Possible origins for the variation in observed barrier characteristics are discussed. Finally, the single electron transistor with two barriers is demonstrated.

Robotic-assisted multivisceral resection for rectal cancer: short-term outcomes at a single center.

BACKGROUND: The safety and feasibility of robotic-assisted multivisceral resection for locally advanced rectal cancer remain unclear. The aim of this study was to assess the short-term outcomes of this procedure at our institution. METHODS: From December 2011 to December 2016, patients who underwent robotic-assisted multivisceral resection for rectal cancer were investigated. Patient demographics, treatment characteristics, perioperative outcomes, and pathological results were evaluated retrospectively. RESULTS: There were 31 patients; 17 men (54.8%) and 14 women (45.2%), with a median age of 65 years (range 40-82 years). Twenty-one patients (67.7%) had a cT4 tumor, 9 patients (29.0%) had a pT4b tumor, and all patients except one (96.8%) underwent complete resection of the primary tumor with negative resection margins. Eleven patients (35.5%) received neoadjuvant chemoradiation. The most commonly resected organ was the vaginal wall (n = 12, 38.7%), followed by the prostate (n = 10, 32.3%). Lateral lymph node dissection was performed in 20 patients (64.5%). The median operative time was 394 min (range 189-549 min), and the median blood loss was 41 mL (range 0-502 mL). None of the patients received intraoperative blood transfusions or required conversion to open. Overall, postoperative complications occurred in 11 patients (35.5%). The most frequent complication was urinary retention (n = 5, 16.1%), and none of the patients developed serious complications classified as Clavien-Dindo grades III-V. CONCLUSIONS: Robotic-assisted multivisceral resection for rectal cancer is safe and technically feasible.