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.

Cervical Spinous Process and Its Attached Muscles Maintain Lower Disk Lordosis: A Retrospective Study of 155 Patients Who Underwent Muscle-Preserving Double Laminectomies

Aoyama Ryoma,Yamane Junichi,Ninomiya Ken,Takahashi Yuichiro,Kitamura Kazuya,Nori Satoshi,Suzuki Satoshi,Shiraishi Tateru 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.5

Study Design: A retrospective study conducted at a single academic institution.Purpose: This study compared the postoperative alignment of consecutive double laminectomies according to their decompression levels and investigated the influence of the extension unit of the spinous process and its attached muscles on postoperative alignment.Overview of Literature: Many reports have investigated bony and soft tissue factors as the causes of postoperative cervical alignment disorders. To-this-date, no other article has clarified the importance of the attached muscles between the spinous processes of C3 and C6 to maintain local cervical alignment.Methods: In total, 155 consecutive patients who underwent muscle-preserving consecutive double laminectomies for cervical spondylotic myelopathy from 2005 to 2013 were included in this study. The imaging parameters included the C2–C7 angle, range of motion, C2–C7 sagittal vertical axis (SVA), C7 slope, C2–C5 angle, C5-C7 angle, local disk angle caudal to the decompression level, and the disk height between C2/C3 and C7/Th1.Results: The caudal disk angle of the decompression level decreased after consecutive double laminectomies, thus suggesting that the extension unit maintained the local lordosis at the lower disk of the decompression level. Postoperatively, in the C3–4 decompression cases, the C2–C7 angle decreased by 7.3°, and the C2–C7 SVA increased by 8.6 mm, thus indicating the appearance of an alignment disorder. Multivariate logistic regression analysis showed that cephalad laminectomy was a risk factor for C2–C7 angle decreases >10°. However, the postoperative recovery rate of Japanese Orthopedic Association scores after consecutive double laminectomies was reasonable, and the overall cervical alignment was well maintained in all decompression levels except C3–C4.Conclusions: The cervical extension unit maintained lordosis at the disk caudal to it. The extension unit was found to contribute more to the maintenance of lordosis of the entire cervical spine at the cephalad side.

Disc Height Narrowing Could Not Stabilize the Mobility at the Level of Cervical Spondylolisthesis: A Retrospective Study of 83 Patients with Cervical Single-Level Spondylolisthesis

Aoyama Ryoma,Yamane Junichi,Ninomiya Ken,Takahashi Yuichiro,Kitamura Kazuya,Nori Satoshi,Suzuki Satoshi,Shiraishi Tateru 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.1

Study Design: A retrospective study at a single academic institution.Purpose: We aimed to understand the pathogenesis of cervical spondylolisthesis by analyzing whether narrowing of the disc height stabilizes the slipped disc level according to the degenerative cascade.Overview of Literature: According to Kirkaldy-Willis’ degenerative cascade, the narrowing of the disc height at slipped level contributes to intervertebral stability in lumbar spondylolisthesis. Conversely, the pathogenesis of cervical spondylolisthesis is unknown due to a scarcity of reports on the condition.Methods: The images of 83 patients with cervical single-level spondylolisthesis were studied. We looked at 52 slipped levels for anterior slippage and 31 for posterior slippage. The imaging parameters included slippage in the neutral, flexed, and extended positions, axial facet joint orientation, sagittal facet slope, global cervical alignment, C2–C7 angle, C2–C7 sagittal vertical axis, range of motion (ROM), and slipped disc angle ROM.Results: With the narrowing of the intervertebral disc height, slippage in the flexed position of both anterior and posterior spondylolisthesis increased. However, in both anterior and posterior spondylolisthesis, disc height narrowing did not show stability. The narrowing of the intervertebral disc height was found to be a risk factor for a translation of slippage of 1.8 mm or more in flexionextension motion in anterior spondylolisthesis in multivariate regression analysis.Conclusions: Narrowing the intervertebral disc height did not stabilize the translation of slippage in flexion-extension motion in cervical spondylolisthesis. Instead, narrowing of the disc height was associated with a translation of slippage of 1.8 mm or more in flexion-extension motion in cases of anterior slippage. Therefore, we discovered that degenerative cascade stabilization for cervical spondylolisthesis was difficult to achieve.

Is simply covering the patient's mouth with a surgical mask during transnasal endoscopy sufficient as an anti-COVID-19 measure?

Yohei Nose,Tomo Ishida,Tomoki Makino,Tsuyoshi Takahashi,Yukinori Kurokawa,Hidetoshi Eguchi,Yuichiro Doki,Kiyokazu Nakajima 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.3

Tumor necrosis factor-α converting enzyme is a key mediator of abdominal aortic aneurysm development

Kaneko, Hidehiro,Anzai, Toshihisa,Horiuchi, Keisuke,Kohno, Takashi,Nagai, Toshiyuki,Anzai, Atsushi,Takahashi, Toshiyuki,Sasaki, Aya,Shimoda, Masayuki,Maekawa, Yuichiro,Shimizu, Hideyuki,Yoshikawa, Tsu Elsevier 2011 Atherosclerosis Vol.218 No.2

<P><B>Abstract</B></P><P><B>Objective</B></P><P>Tumor necrosis factor (TNF)-α is known to be elevated in plasma and the aorta in abdominal aortic aneurysm (AAA) patients. We sought to clarify the role of TNF-α converting enzyme (Tace), which cleaves the transmembrane precursor of TNF-α, in AAA development.</P><P><B>Methods</B></P><P>We obtained aortic sample of AAA during surgical operation to assess the histological features and protein expression of human AAA. AAA was induced in mice with temporal systemic deletion of Tace by the inducible Mx-1 Cre transgene (TaceMx1) and in wild-type littermates (CON) by periaortic application of CaCl<SUB>2</SUB> (AAA/TaceMx1, AAA/CON).</P><P><B>Results</B></P><P>Tace expression was increased in human AAA samples as compared with normal aorta. Six weeks postoperatively, aortic diameter in AAA/TaceMx1 was decreased than in AAA/CON in association with attenuated TNF-α expression and extracellular matrix disruption. Increased activities of matrix metalloproteinase (MMP)-9 and MMP-2, numbers of Mac-2-positive macrophages, CD3-positive T lymphocytes and CD31-positive vessels in periaortic tissues, mRNA expression of CD68, monocyte chemotactic protein-1, TNF-α, vascular endothelial growth factor-A, p47 and glutathione peroxidases, and protein expression of phospho-c-Jun N-terminal kinase in AAA were all attenuated by Tace deletion. Protein expression of transforming growth factor (TGF)-β1 was upregulated by Tace deletion in sham-operated mice. TGF-β1 expression was further increased in AAA/TaceMx1.</P><P><B>Conclusions</B></P><P>Tace was overexpressed in the aortic wall in human and experimental AAA. Temporal systemic deletion of Tace prevented AAA development in association with attenuating inflammation, oxidative stress, neoangiogenesis and extracellular matrix disruption, suggesting a crucial role of Tace in AAA development.</P>