Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy.

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire. Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet's content and quality, respondents' satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale. Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet. Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

Comment on "An early Miocene extinction in pelagic sharks".

Sibert and Rubin (Reports, 4 June 2021, p. 1105) claim to have identified a previously unidentified, major extinction event of open-ocean sharks in the early Miocene. We argue that their interpretations are based on an experimental design that does not account for a considerable rise in the sedimentation rate coinciding with the proposed event, nor for intraspecific variation in denticle morphology.

Orbital Complexity in Intrinsic Magnetic Topological Insulators MnBi_{4}Te_{7} and MnBi_{6}Te_{10}.

Using angle-resolved photoelectron spectroscopy (ARPES), we investigate the surface electronic structure of the magnetic van der Waals compounds MnBi_{4}Te_{7} and MnBi_{6}Te_{10}, the n=1 and 2 members of a modular (Bi_{2}Te_{3})_{n}(MnBi_{2}Te_{4}) series, which have attracted recent interest as intrinsic magnetic topological insulators. Combining circular dichroic, spin-resolved and photon-energy-dependent ARPES measurements with calculations based on density functional theory, we unveil complex momentum-dependent orbital and spin textures in the surface electronic structure and disentangle topological from trivial surface bands. We find that the Dirac-cone dispersion of the topologial surface state is strongly perturbed by hybridization with valence-band states for Bi_{2}Te_{3}-terminated surfaces but remains preserved for MnBi_{2}Te_{4}-terminated surfaces. Our results firmly establish the topologically nontrivial nature of these magnetic van der Waals materials and indicate that the possibility of realizing a quantized anomalous Hall conductivity depends on surface termination.

Reduction of Pneumocystis jirovecii pneumonia and bloodstream infections by trimethoprim-sulfamethoxazole prophylaxis in patients with rheumatic diseases.

Objective: Trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is routinely administered to patients with rheumatic diseases in Japan. The present study aimed to evaluate the effect of TMP/SMX prophylaxis on PJP and non-central line-associated bloodstream infections (BSIs) in patients receiving high-dose glucocorticoids for the treatment of rheumatic diseases.Method: This study enrolled patients who were admitted between 1 October 2003 and 31 March 2018 and began high-dose glucocorticoid therapy for rheumatic diseases during hospitalization. The observation period was 4 months from the commencement of high-dose glucocorticoid therapy. The effect of TMP/SMX prophylaxis on PJP and non-central line-associated BSI was analysed.Results: Of the 437 patients included in the study, 376 received TMP/SMX prophylaxis and 61 patients did not. During the observation period, TMP/SMX prophylaxis was discontinued in 76 patients (20.2%). Three PJP cases (0.7%) occurred. Among the 399 patients included in our analysis of non-central line-associated BSI, eight experienced non-central line-associated BSI (2.0%). Among the covariates, TMP/SMX prophylaxis was associated with reduced PJP and non-central line-associated BSI incidence [odds ratio (OR) 0, 95% confidence interval (CI) 0.00-0.38, and OR 0.08, 95% CI 0.01-0.42, respectively].Conclusion: Routine TMP/SMX prophylaxis reduced the incidence of both PJP and BSI in patients with rheumatic diseases undergoing high-dose glucocorticoid therapy.

Regulation of nursing professionals in Cambodia: strategies to overcome underpinning challenges.

AIMS: To elucidate (i) the challenges and constraints in the development and implementation of the regulatory framework for nursing professionals in Cambodia and (ii) the specific strategies adopted to address the challenges experienced in Cambodia. INTRODUCTION: The health workforce will be critical to achieving the health-related and wider Sustainable Development Goals in the years up to 2030. BACKGROUND: In 2006, the countries of the Association of Southeast Asian Nations signed a Mutual Recognition Arrangement in relation to nursing services in the region with the main aim of facilitating the mobility of nursing professionals between countries. To ensure the competency of the health workforce and the quality and safety of health services, member states are required to establish an appropriate regulatory framework. METHODS: This is a qualitative descriptive study. Eighteen key informant interviews were conducted in Cambodia in 2018. Walt and Gilson's policy analysis model was applied to organize and synthesize the data. FINDINGS: Major challenges were identified such as conceptual and cultural issues, limited capacity of Cambodian stakeholders and an unstandardized system with limited coordination. DISCUSSION: In Cambodia, the nursing regulatory environment has expanded greatly over the last decade. Strategies adopted were 'political leadership', optimal utilization of 'outsider's capacity', strengthening 'insider's capacity', and 'dedicated consultation and collaboration and consensus building' involving all players. IMPLICATIONS FOR NURSING AND HEALTH POLICIES: Policymakers in similar resource-limited countries could apply and adapt similar strategic efforts when formulating and implementing health policies, legislation and regulations. 'Outsiders', in this case, represented by development partners can play a vital role in the process, but should not be leading the charge. They should be aligned with national priority to support recipient countries. It is imperative for these countries and development partners to invest in increasing the quantity and quality of nursing leaders who can develop and advance regulatory functions.

Reversal of freshening trend of Antarctic Bottom Water in the Australian-Antarctic Basin during 2010s.

The Antarctic continental margin supplies the densest bottom water to the global abyss. From the late twentieth century, an acceleration in the long-term freshening of Antarctic Bottom Waters (AABW) has been detected in the Australian-Antarctic Basin. Our latest hydrographic observations reveal that, in the late 2010s, the freshening trend has reversed broadly over the continental slope. Near-bottom salinities in 2018-2019 were higher than during 2011-2015. Along 170° E, the salinity increase between 2011 and 2018 was greater than that observed in the west. The layer thickness of the densest AABW increased during the 2010s, suggesting that the Ross Sea Bottom Water intensification was a major source of the salinity increase. Freshwater content on the continental slope decreased at a rate of 58 ± 37 Gt/a in the near-bottom layer. The decadal change is very likely due to changes in Ross Sea shelf water attributable to a decrease in meltwater from West Antarctic ice shelves for the corresponding period.

The utility of patent ductus arteriosus closure with hemostatic clip in dogs.

This study investigated the utility of patent ductus arteriosus (PDA) closure with hemostatic clip by comparing with traditional PDA closure. Medical records of 51 dogs with surgical closure of PDA were reviewed and retrospective study was conducted. 29 dogs were treated by procedure with hemostatic clip (Group HC), and 22 dogs were treated by surgical ligation (Group SL). Data pertaining to breed, sex, age and body weight at the time of surgery, echocardiographic minimal ductal diameter, duration of surgery, hemostatic clip size, echocardiographic findings, hemor-rhage, residual ductal flow and recanalization were collected from records. The results showed that procedure with hemostatic clip had been selected in lighter dogs than traditional PDA closure. Duration of surgery performed only hemostatic clip technique was significantly shorter than that in group SL. Preoperative LVIDd, E-wave and FS were significantly lower than postoperative ones. As regard all parameters, the differences between pre- and postoperative periods were not significantly different between group HC and group SL. Hemorrhage, residual ductal flow, and recanalization were not significantly different in both groups. The present study showed that procedure with hemostatic clip is beneficial in that it is available in smaller dogs and can make shorter operation duration than traditional PDA closure. Moreover, the procedure is effective for the resolution of volume overload of the left atrium and ventricle in short-term outcome. Complications including hemorrhage, residual ductal flow and recanaliza-tion were not significantly different with both techniques.

Roles of Re-entrant cluster glass state and spin-lattice coupling in magneto-dielectric behavior of giant dielectric double perovskite La1.8Pr0.2CoFeO6.

La based Co-Fe combined double perovskite (La1.8Pr0.2CoFeO6) was synthesized and the dielectric (zero-field and in-field), magnetic, x-ray absorption and Raman spectroscopy measurements have been investigated for La1.8Pr0.2CoFeO6 double perovskite. The existence of re-entrant cluster glass state is observed. The magneto-dielectric (MD) is found in two temperature regions (25-80 K and 125-275 K). It has been demonstrated that the observed MD at low and high temperatures are respectively due to the spin freezing and the spin-lattice coupling. Furthermore, the very large dielectric constant and the low loss suggest that La1.8Pr0.2CoFeO6 is very important from the application point of view.

Anomalous Hall effect in Cu doped Bi2Te3 topological insulator.

The angle resolved photo-emission spectroscopy (ARPES) study and magneto-transport properties of Bi2Cu x Te3-x have been investigated. ARPES study indicates the clear existence of surface states in the as-prepared samples. The estimated bandgap from ARPES is found to be ∼5 meV and 16 meV respectively for x = 0.03 and x = 0.15 samples. Presence of larger Cu concentration (x = 0.15) introduces magnetic ordering. Observed non-linearity in the Hall data is due to the existence of anomalous Hall effect which can be attributed to the 2D transport. The observed magneto-transport features might be related to the surface carriers which is confirmed by ARPES study.

Arthroscopic release for the severely stiff elbow.

BACKGROUND: Arthroscopic release for the stiff elbow has been widely used, but there are no reports limited to severe stiffness. The purpose of this study was to investigate the outcomes of severe cases. MATERIALS AND METHODS: Ten patients with 10 severely stiff elbows defined by a limited arc of ≤ 60° underwent this arthroscopic release. Causes of stiffness were post-traumatic stiffness (one patient), osteoarthritis (three patients), and rheumatoid arthritis (six patients). Using arthroscopy, the capsule contracture and the intra-articular fibrosis were removed and the impinging osteophyte and part of the radial head were resected. For four patients with preoperative ulnar nerve symptoms or contracture of the posterior oblique ligament of the medial collateral ligament, mini-open ulnar nerve neurolysis and release of the posterior oblique ligament were performed. Patients were followed up for an average of 24 months. RESULTS: Arthroscopic release could be performed without any intraoperative complications. Range of motion for the elbow significantly improved from 95° of flexion and - 55° of extension to 109° of flexion and - 32° of extension. The Mayo Elbow Performance Score also improved from 56 points to 80 points. Two patients underwent a second arthroscopic surgery and gained further arc of motion. One patient showed osteophyte reformation and needed revision open surgery 1 year after the initial surgery. CONCLUSIONS: Arthroscopic release for the severely stiff elbow could improve range of motion. Careful attention should be given during surgery to avoid complications such as intramuscular bleeding or nerve damage.

IL-1-dependent electrophysiological changes and cardiac neural remodeling in a mouse model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. In addition to coronary artery abnormalities, aneurysms and myocarditis, acute KD is also associated with echocardiogram (ECG) abnormalities in 40-80% of patients. Here, we show that these ECG changes are recapitulated in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. LCWE-injected mice developed elevated heart rate and decreased R wave amplitude, with significant differences in prolonged ventricular repolarization. LCWE-injected mice developed cardiac ganglion inflammation, that may affect the impulse-conducting system in the myocardium. Furthermore, serum nerve growth factor (NGF) was significantly elevated in LCWE-injected mice, similar to children with KD vasculitis, associated with increased neural remodeling of the myocardium. ECG abnormalities were prevented by blocking interleukin (IL)-1 signaling with anakinra, and the increase in serum NGF and cardiac neural remodeling were similarly blocked in Il1r1-/- mice and in wild-type mice treated with anakinra. Thus, similar to clinical KD, the LCWE-induced KD vasculitis mouse model also exhibits electrophysiological abnormalities and cardiac neuronal remodeling, and these changes can be prevented by blocking IL-1 signaling. These data support the acceleration of anti-IL-1 therapy trials to benefit KD patients.

Spectroscopic Evidence for Electron-Boson Coupling in Electron-Doped Sr_{2}IrO_{4}.

The pseudogap, d-wave superconductivity and electron-boson coupling are three intertwined key ingredients in the phase diagram of the cuprates. Sr_{2}IrO_{4} is a 5d-electron counterpart of the cuprates in which both the pseudogap and a d-wave instability have been observed. Here, we report spectroscopic evidence for the presence of the third key player in electron-doped Sr_{2}IrO_{4}: electron-boson coupling. A kink in nodal dispersion is observed with an energy scale of ∼50 meV. The strength of the kink changes with doping, but the energy scale remains the same. These results provide the first noncuprate platform for exploring the relationship between the pseudogap, d-wave instability, and electron-boson coupling in doped Mott insulators.

Simple dose-escalation regimen for hydroxychloroquine-induced hypersensitivity reaction in patients with systemic lupus erythematosus enabled treatment resumption.

OBJECTIVE: This study aimed to investigate the risk factors of hydroxychloroquine (HCQ)-induced hypersensitivity in patients with systemic lupus erythematosus (SLE) and to propose a simple dose-escalation regimen in cases of mild HCQ-induced hypersensitivity. METHODS: We identified patients with SLE who started HCQ between 2009 and 2018 and cases of HCQ-induced hypersensitivity by reviewing the electronic medical charts. A simple dose-escalation regimen, starting at 40 mg/day with weekly increments of 40 mg/day to 200 mg/day, was used in patients with HCQ-induced hypersensitivity who did not require hospitalization or systemic steroid therapy. We then compared the clinical parameters of patients with and without HCQ-induced hypersensitivity and evaluated the success of our dose-escalation regimen. RESULTS: We enrolled 302 patients with SLE and identified 25 cases of HCQ-induced eruption (8.3%). The mean Naranjo score of these patients was 5.1 ± 1.4 (min 3, max 8), and all 25 patients received a 'possible' (9) or 'probable' (16) score. A mild, generalized, maculopapular rash occurred in 24 patients, and urticaria occurred in one patient at 24 days (interquartile range 15-40 days) after the start of treatment. The proportion of cyclophosphamide use, glucocorticoid consisting of prednisolone 20 mg/day or more, and initiation of SMX-TMP within 28 days were higher in patients with skin eruptions. On multivariate analysis, only cyclophosphamide use was identified as a risk factor of HCQ-induced hypersensitivity (odds ratio = 12.3 (95% confidential interval 1.4-14.3)). Thirteen of the 14 patients on the dose-escalation regimen (92.9%) tolerated continued HCQ treatment. One patient re-experienced eruptions on day 10 day after starting HCQ. CONCLUSIONS: Mild late reactions are common in HCQ-induced hypersensitivity. A simpler dose-escalation regimen enables safe and easier reintroduction of HCQ but should not be applied to patients with immediate reactions or moderate late reactions.

Feasibility of resecting the portal vein only when necessary during pancreatoduodenectomy for pancreatic cancer.

Background: Whether the portal/superior mesenteric vein (PV) should be resected during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) based on preoperative CT or intraoperative findings is controversial. Methods: This was a retrospective study with data of patients who had undergone pancreatoduodenectomy for PDAC between 2002 and 2016 in a tertiary referral centre. Based on the extent of contact between the PV and tumour on CT, patients were categorized into: group 1, no contact; group 2, contact 180° or less; group 3, contact greater than 180°. Extent of pathological PV invasion (pPV) (no invasion, pv0; invasion to tunica adventitia, pv1; invasion to media, pv2; invasion to intima, pv3) was compared with patient survival. To assess the feasibility of performing PV resection (PVR) based on intraoperative findings, the prognosis of patients in groups 1 and 2 with pv0 and no PVR (PVR(-)pv0) was compared with that of patients who had PVR (PVR(+)pv0), selected using propensity score matching. Results: Groups 1, 2 and 3 comprised 230, 232 and 38 patients respectively, and PVR was performed in 10·9, 73·3 and 95 per cent of them (P < 0·001). Extent of pPV differed significantly (P < 0·001). The positive predictive value of radiological tumour contact with PV in predicting positive pPV was 42·6 per cent. In 64 patients with PVR(-)pv0 and 64 matched patients with PVR(+)pv0, the R0 resection rate (66 versus 73 per cent respectively; P = 0·337) and survival (median 32·4 versus 32·1 months; P = 0·780) were not significantly different. Conclusion: PVR is needed only when the tumour is in clear contact with the PV and cannot be detached during surgery.

Investigation of multi-mode spin-phonon coupling and local B-site disorder in Pr2CoFeO6 by Raman spectroscopy and correlation with its electronic structure by XPS and XAS studies.

Electronic structure of Pr2CoFeO6 (at 300 K) was investigated by x-ray photoemission spectroscopy (XPS) and x-ray absorption spectroscopy techniques. All three cations, i.e. Pr, Co and Fe were found to be trivalent in nature. XPS valance band analysis suggested the system to be insulating in nature. The analysis suggested that Co3+ ions exist in low spin state in the system. Moreover, Raman spectroscopy study indicated the random distribution of the B-site ions (Co/Fe) triggered by same charge states. In temperature-dependent Raman study, the relative heights of the two observed phonon modes exhibited anomalous behaviour near magnetic transition temperature T N ~ 270 K, thus indicating towards interplay between spin and phonon degrees of freedom in the system. Furthermore, clear anomalous softening was observed below T N which confirmed the existence of strong spin-phonon coupling occurring for at least two phonon modes of the system. The line width analysis of the phonon modes essentially ruled out the role of magnetostriction effect in the observed phonon anomaly. The investigation of the lattice parameter variation across T N (obtained from the temperature-dependent neutron diffraction measurements) further confirmed the existence of the spin-phonon coupling.

Dirac gap opening and Dirac-fermion-mediated magnetic coupling in antiferromagnetic Gd-doped topological insulators and their manipulation by synchrotron radiation.

A new kind of magnetically-doped antiferromagnetic (AFM) topological insulators (TIs) with stoichiometry Bi1.09Gd0.06Sb0.85Te3 has been studied by angle-resolved photoemission spectroscopy (ARPES), superconducting magnetometry (SQUID) and X-ray magnetic circular dichroism (XMCD) with analysis of its electronic structure and surface-derived magnetic properties at different temperatures. This TI is characterized by the location of the Dirac gap at the Fermi level (EF) and a bulk AFM coupling below the Neel temperature (4-8 K). At temperatures higher than the bulk AFM/PM transition, a surface magnetic layer is proposed to develop, where the coupling between the magnetic moments located at magnetic impurities (Gd) is mediated by the Topological Surface State (TSS) via surface Dirac-fermion-mediated magnetic coupling. This hypothesis is supported by a gap opening at the Dirac point (DP) indicated by the surface-sensitive ARPES, a weak hysteresis loop measured by SQUID at temperatures between 30 and 100 K, XMCD measurements demonstrating a surface magnetic moment at 70 K and a temperature dependence of the electrical resistance exhibiting a mid-gap semiconducting behavior up to temperatures of 100-130 K, which correlates with the temperature dependence of the surface magnetization and confirms the conclusion that only TSS are located at the EF. The increase of the TSS's spectral weight during resonant ARPES at a photon energy corresponding to the Gd 4d-4f edge support the hypothesis of a magnetic coupling between the Gd ions via the TSS and corresponding magnetic moment transfer at elevated temperatures. Finally, the observed out-of-plane and in-plane magnetization induced by synchrotron radiation (SR) due to non-equal depopulation of the TSS with opposite momentum, as seen through change in the Dirac gap value and the k∥-shift of the Dirac cone (DC) states, can be an indicator of the modification of the surface magnetic coupling mediated by the TSS.

Acquired undescended testis and possibly associated testicular torsion in children with cerebral palsy or neuromuscular disease.

INTRODUCTION: Torsion of an undescended testis (UDT) associated with cerebral palsy (CP) and neuromuscular disease (NMD) is an uncommon condition that is not well recognized by primary care physicians or healthcare providers. OBJECTIVE: The objective of this study was to highlight the clinical importance of torsion of a UDT in children with CP and NMD. MATERIALS AND METHODS: Eleven children with testicular torsion of a UDT operated on at the study institute between 1991 and 2015 were identified. The records of seven children (63.6%) associated with CP or NMD were retrospectively reviewed. Clinical findings of testicular torsion were assessed along with the treatment outcome and testicular salvageability. RESULTS: All seven children were not identified with a UDT by public health checkup for infant and young children. No children with CP or NMD had torsion of a descended testis during the present study period. Median age at surgery was 15 years (range, 1-20 years). The testis location was at the external inguinal ring in five patients, in the inguinal canal in one, and in the superficial inguinal pouch in one. Of the contralateral testes, four were a UDT, one was a retractile testis, and two were descended testes. Orchiectomy was performed in six patients (85.7%). In the remaining patients, the testis was preserved but became atrophic. DISCUSSION: This study demonstrated that children with CP or NMD may be affected with torsion of a UDT with peak at around puberty with the poor salvage rate, even if the testes appear descended in infancy and young children. Shortcomings of this study were the retrospective design and a small series of children undergoing surgery for torsion of a UDT. CONCLUSION: Pediatric urologists need to educate primary care physicians and healthcare providers in the recognition of acquired UDTs and possibly associated testicular torsion in children with CP and NMD. Genital examination should be continued regularly until adolescence in these children to detect acquired UDT. These children should be referred to pediatric urologists to promote surgery as soon as the diagnosis of acquired UDT is carried out. It is believed that it is perhaps the best approach to prevent loss of the testis in children with CP and NMD.

Extent of lymph node dissection in patients with gallbladder cancer.

BACKGROUND: Definitions of regional lymph nodes for gallbladder cancer differ according to staging system. Hence, the appropriate extent of lymph node dissection has not yet been standardized. METHODS: Pathological stages and disease-specific survival (DSS) of patients who had undergone surgical resection of gallbladder cancer between 1990 and 2016 were reviewed. Patients with nodal metastases limited to the hepatoduodenal ligament or common hepatic artery, extending to the posterosuperior pancreatic head lymph nodes (PSPLNs), or in nodes along the coeliac axis or superior mesenteric vessels were grouped as having Na, Nb and Nc disease respectively. Metastases beyond these regions were defined as distant metastases (M1). Absence of distant metastasis was expressed as M0. RESULTS: A total of 259 patients were evaluated. There were 74, 31 and nine patients respectively in the Na, Nb and Nc groups. Twenty-five, nine and four patients in the respective groups had M1 disease (P = 0·682). The 5-year DSS rate was comparable between patients with Na M0 and those with Nb M0 disease (36 versus 34 per cent respectively; P = 0·950), whereas the rate in patients with Nc M0 status (0 per cent) was worse than that of patients with Nb M0 (P = 0·017) and comparable to that of patients with M1 disease (14 per cent; P = 0·590). Among 22 patients with Nb M0 disease, the 5-year DSS rate did not differ between those who had undergone pancreatoduodenectomy and those who had had dissection of PSPLNs without pancreatoduodenectomy (50 versus 30 per cent respectively; P = 0·499). CONCLUSION: PSPLNs and nodes along the hepatoduodenal ligament and hepatic artery should be considered regional nodes for gallbladder cancer, and should be resected.

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.