Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial

Kato, Ken,Cho, Byoung Chul,Takahashi, Masanobu,Okada, Morihito,Lin, Chen-Yuan,Chin, Keisho,Kadowaki, Shigenori,Ahn, Myung-Ju,Hamamoto, Yasuo,Doki, Yuichiro,Yen, Chueh-Chuan,Kubota, Yutaro,Kim, Sung-Ba ELSEVIER 2019 LANCET ONCOLOGY Vol.20 No.11

<P><B>Summary</B></P> <P><B>Background</B></P> <P>Chemotherapy for patients with advanced oesophageal squamous cell carcinoma offers poor long-term survival prospects. We report the final analysis from our study of the immune checkpoint PD-1 inhibitor nivolumab versus chemotherapy in patients with previously treated advanced oesophageal squamous cell carcinoma.</P> <P><B>Methods</B></P> <P>We did a multicentre, randomised, open-label, phase 3 trial (ATTRACTION-3) at 90 hospitals and cancer centres in Denmark, Germany, Italy, Japan, South Korea, Taiwan, the UK, and the USA. We enrolled patients aged 20 years and older with unresectable advanced or recurrent oesophageal squamous cell carcinoma (regardless of PD-L1 expression), at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a baseline Eastern Cooperative Oncology Group performance status of 0–1, and who were refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy and had a life expectancy of at least 3 months. Patients were randomly assigned (1:1) to either nivolumab (240 mg for 30 min every 2 weeks) or investigator's choice of chemotherapy (paclitaxel 100 mg/m<SUP>2</SUP> for at least 60 min once per week for 6 weeks then 1 week off; or docetaxel 75 mg/m<SUP>2</SUP> for at least 60 min every 3 weeks), all given intravenously. Treatment continued until disease progression assessed by the investigator per RECIST version 1.1 or unacceptable toxicity. Randomisation was done using an interactive web response system with a block size of four and stratified according to geographical region (Japan <I>vs</I> rest of the world), number of organs with metastases, and PD-L1 expression. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival, defined as the time from randomisation until death from any cause, in the intention-to-treat population that included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT02569242, and follow-up for long-term outcomes is ongoing.</P> <P><B>Findings</B></P> <P>Between Jan 7, 2016, and May 25, 2017, we assigned 419 patients to treatment: 210 to nivolumab and 209 to chemotherapy. At the time of data cutoff on Nov 12, 2018, median follow-up for overall survival was 10·5 months (IQR 4·5–19·0) in the nivolumab group and 8·0 months (4·6–15·2) in the chemotherapy group. At a minimum follow-up time (ie, time from random assignment of the last patient to data cutoff) of 17·6 months, overall survival was significantly improved in the nivolumab group compared with the chemotherapy group (median 10·9 months, 95% CI 9·2–13·3 <I>vs</I> 8·4 months, 7·2–9·9; hazard ratio for death 0·77, 95% CI 0·62–0·96; p=0·019). 38 (18%) of 209 patients in the nivolumab group had grade 3 or 4 treatment-related adverse events compared with 131 (63%) of 208 patients in the chemotherapy group. The most frequent grade 3 or 4 treatment-related adverse events were anaemia (four [2%]) in the nivolumab group and decreased neutrophil count (59 [28%]) in the chemotherapy group. Five deaths were deemed treatment-related: two in the nivolumab group (one each of interstitial lung disease and pneumonitis) and three in the chemotherapy group (one each of pneumonia, spinal cord abscess, and interstitial lung disease).</P> <P><B>Interpretation</B></P> <P>Nivolumab was associated with a significant improvement in overall survivaland a favourable safety profile compared with chemotherapy in previously treated patients with advanced oesophageal squamous cell carcinoma, and might represent a new standard second-line treatment option for these patients.

Anatomical liver resection using Laennec system

Atsushi Sugioka,Yutaro Kato,Yoshinao Tanahashi,Tadashi Kagawa,Gozo Kiguchi,Masayuki Kojima,Akira Yasuda,Sanae Nakajima,Syo-ichiro Tsuji,Ichiro Uyama 한국간담췌외과학회 2017 한국간담췌외과학회 학술대회지 Vol.2017 No.3

Laparoscopic and Robotic Liver Resection Using Advanced 3D Liver Simulation Software

( Atsushi Sugioka ),( Yutaro Kato ),( Yoshinao Tanahashi ),( Tadashi Kagawa ),( Masayuki Kojima ),( Sanae Nakajima ),( Syo-ichiro Tsuji ),( Ichiro Uyama ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Minimally invasive liver resection including laparoscopic and robotic liver resection is a rapidly developing field withthe greatest potential. However, the spatial disorientation is one of the biggest issues that would increase the risk of dangerousbleeding and bile leakage. To overcome this issue, it is of crucial importance to standardize anatomical liver resection with extrahepaticGlissonean pedicle-first approach and to use advanced 3D liver simulation software that can visualize the Glissoneansystem.Methods: We proposed a novel concept of liver anatomy based on Laennec’s capsule that can standardize the extrahepaticGlissonean pedicle approach. Whereas Synapse 3D® is the first simulation software to use face recognition technology for clinical3D simulation and visualization of the Glissonean system are available since version 4.4.Results: Owing to the novel concept of liver anatomy, anatomical liver resection with extrahepatic Glissonean pedicle-first approachwas standardized and target area was well recognized prior to parenchymal dissection with minimal bleeding and bileleakage from the resecting plane. Preoperative 3D simulation and intraoperative navigation contributed to perform systematicanatomical liver resection without spatial disorientation even for the cases with anatomical abnormalities such as right-sidedligamentum teres.Conclusion: Minimally invasive liver resection including laparoscopic and robotic resection became safe and curable procedureswith the novel concept of liver anatomy and advanced 3D liver simulation.

Standardization of surgical techniques for cholangiocarcinoma based on Laennec’s capsule

Atsushi Sugioka,Yutaro Kato,Yoshinao Tanahashi,Tadashi Kagawa,Gozo Kiguchi,Masayuki Kojima,Akira Yasuda,Sanae Nakajima,Syo-ichiro Tsuji,Zenichi Morise,Ichiro Uyama 한국간담췌외과학회 2017 한국간담췌외과학회 학술대회지 Vol.2017 No.3

miniTAO/ANIR Paα SURVEY OF LOCAL LIRGs

Tateuchi, Ken,Motohara, Kentaro,Konishi, Masahiro,Takahashi, Hidenori,Kato, Natsuko,Uchimoto, Yuka K.,Toshikawa, Koji,Ohsawa, Ryou,Kitagawa, Yutaro,Yoshii, Yuzuru,Doi, Mamoru,Kohno, Kotaro,Kawara, Kim The Korean Astronomical Society 2012 天文學論叢 Vol.27 No.4

ANIR (Atacama Near InfraRed camera) is a near infrared camera for the University of Tokyo Atacama 1m telescope, installed at the summit of Co. Chajnantor (5,640 m altitude) in northern Chile. The high altitude and extremely low water vapor (PWV = 0.5 mm) of the site enable us to perform observation of hydrogen $Pa{\alpha}$ emission line at $1.8751{\mu}m$. Since its first light observation in June 2009, we have been carrying out a $Pa{\alpha}$ narrow-band imaging survey of nearby luminous infrared galaxies (LIRGs), and have obtained $Pa{\alpha}$ for 38 nearby LIRGs listed in AKARI/FIS-PSC at the velocity of recession between 2,800 km/s and 8,100 km/s. LIRGs are affected by a large amount of dust extinction ($A_V$~ 3 mag), produced by their active star formation activities. Because $Pa{\alpha}$ is the strongest hydrogen recombination line in the infrared wavelength ranges, it is a good and direct tracer of dust-enshrouded star forming regions, and enables us to probe the star formation activities in LIRGs. We find that LIRGs have two star-forming modes. The origin of the two modes probably come from differences between merging stage and/or star-forming process.

Mucus Plugs and Small Airway Dysfunction in Asthma, COPD, and Asthma-COPD Overlap

Tamura Kanami,Shirai Toshihiro,Hirai Keita,Nakayasu Hiromasa,Takahashi Shingo,Kishimoto Yutaro,Akamatsu Taisuke,Asada Kazuhiro,Kato Satoshi 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.2

Purpose: There are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study. Methods: Subjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs. Results: Mucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population. Conclusions: SAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.