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"Sakai, Daisuke"
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Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer
by
Kojima, Akihito
,
Kawakami, Hisato
,
Ryu, Min-Hee
in
Adenocarcinoma
,
Adenocarcinoma - drug therapy
,
Adult
2020
Approximately 15 to 20% of gastric adenocarcinomas express HER2. Trastuzumab deruxtecan is an antibody-drug conjugate composed of trastuzumab and the topoisomerase I inhibitor deruxtecan. In a randomized trial, the antibody-drug conjugate led to higher response and longer overall survival than physician’s choice of therapy among patients with relapsed disease.
Journal Article
Short-term comparison of preoperative and postoperative pain after indirect decompression surgery and direct decompression surgery in patients with degenerative spondylolisthesis
2020
The purpose of this study was to compare the short-term clinical outcomes between extreme lateral interbody fusion (XLIF) and minimally invasive surgery (MIS)–transforaminal interbody fusion (TLIF) in patients with degenerative spondylolisthesis with stenosis. One hundred-six patients were enrolled; 44 were treated with MIS–TLIF (direct decompression group; DP), and 62 were treated with XLIF (indirect decompression group; IDP). Perioperative indexes included operation time and intraoperative bleeding. Perioperative indexes preoperative and postoperative numeric rating scale (NRS) scores for low back pain (NRS-BP), leg pain (NRS-LP), and leg numbness (NRS-LN), and the preoperative score on the Japanese version of the painDETECT questionnaire (PDQ-J) were also assessed. The average follow-up period for the collection of NRS scores was 12.6 months. The operation time was significantly shorter in the IDP than in the DP group (109.9 ± 35.4 vs. 153.3 ± 50.9 min;
p
< 0.001). Intraoperative blood loss was also significantly less in the IDP group than in the DP group (85.4 ± 125.4 vs. 258.3 ± 220.4 mL;
p
< 0.001). The PDQ-J score and preoperative NRS scores (NRS-BP, NRS-LP, and NRS-LN) did not differ significantly between groups. Less improvement in the NRS-BP (ΔNRS-BP) was observed in the DP group than in the IDP group (
p
< 0.05). Although pain improved after surgery in both groups, IDP surgery was advantageous in minimizing bleeding and preserving posterior support elements such as the facet joints, lamina, and paraspinal muscles. These findings suggest that this may have contributed to the higher rate of improvement in low back pain compared with DP surgery.
Journal Article
Chronological improvement in precision oncology implementation in Japan
by
Sakai, Daisuke
,
Ennishi, Daisuke
,
Komine, Keigo
in
Clinical trials
,
comprehension genomic profiling test
,
Drugs
2022
In Japan, comprehensive genomic profiling (CGP) tests for refractory cancer patients have been approved since June 2019, under the requirement that all cases undergoing CGP tests are annotated by the molecular tumor board (MTB) at each government‐designated hospital. To investigate improvement in precision oncology, we evaluated and compared the proportion of cases receiving matched treatments according to CGP results and those recommended to receive genetic counseling at all core hospitals between the first period (11 hospitals, June 2019 to January 2020) and second period (12 hospitals, February 2020 to January 2021). A total of 754 and 2294 cases underwent CGP tests at core hospitals in the first and second periods, respectively; 28 (3.7%) and 176 (7.7%) patients received matched treatments (p < 0.001). Additionally, 25 (3.3%) and 237 (10.3%) cases were recommended to receive genetic counseling in the first and second periods, respectively (p < 0.001). The proportion was associated with the type of CGP test: tumor‐only (N = 2391) vs. tumor‐normal paired (N = 657) analysis (10.0% vs. 3.5%). These results suggest that recommendations regarding available clinical trials in networked MTBs might contribute to increasing the numbers of matched treatments, and that tumor‐normal paired rather than tumor‐only tests can increase the efficiency of patient referrals for genetic counseling. We investigated the improvement in precision oncology by evaluating and comparing the proportion of patients receiving genomically‐matched therapies and referred to genetic counseling among all designated core hospitals between two study periods (First period: 11 hospitals, June 2019 to January 2020; Second period: 12 hospitals, February 2020 to January 2021). Our results revealed that both the proportion of matched therapies and referrals to genetic counseling improved chronologically, from 3.7% to 7.7% (p 0.001) and 3.3% to 10.3% (p 0.001), respectively.
Journal Article
IVD progenitor cells: a new horizon for understanding disc homeostasis and repair
2019
Intervertebral disc (IVD) degeneration is associated with low back pain. In IVDs, a high mechanical load, high osmotic pressure and hypoxic conditions create a hostile microenvironment for resident cells. How IVD homeostasis and function are maintained under stress remains to be understood; however, several research groups have reported isolating native endogenous progenitor-like or otherwise proliferative cells from the IVD. The isolation of such cells implies that the IVD might contain a quiescent progenitor-like population that could be activated for IVD repair and regeneration. Increased understanding of endogenous disc progenitor cells will improve our knowledge of IVD homeostasis and, when combined with tissue engineering techniques, might hold promise for future therapeutic applications. In this Review, the characteristics of progenitor cells in different IVD compartments are discussed, as well as the potency of different cell populations within the IVD. The stem cell characteristics of these cells are also compared with those of mesenchymal stromal cells. On the basis of existing evidence, whether and how IVD degeneration and the hostile microenvironment might affect endogenous progenitor cell function are considered, and ways to channel the potential of these cells for IVD repair are suggested.Intervertebral disc degeneration is a leading cause of low back pain. Endogenous progenitor cells are still being fully characterized but hold promise for future regeneration strategies.
Journal Article
The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan
by
Naito Yoichi
,
Aimono Eriko
,
Koyama Takafumi
in
Clinical trials
,
Genetic counseling
,
Hospitals
2021
BackgroundSince June 2019, cancer genomic profiling (CGP) tests have been reimbursed by the National Health Insurance system in Japan, with restrictions for government-designated hospitals with a molecular tumor board composed of multidisciplinary specialists, known as an expert panel (EP). The standardization of EPs is a critical challenge for implementing precision oncology in the clinical setting.MethodsData on consecutive cases who underwent the CGP tests at 11 core hospitals between June 2019 and January 2020 were collected. We evaluated the proportions of cases that received genomically matched treatments, including investigational new drugs (INDs) based on CGP results, and/or for which genetic counseling was recommended. Two simulated cases were annotated by each EP. The annotated reports were then centrally assessed.ResultsEach EP mainly discussed the applicability to genomically matched treatments and the necessity of performing genetic counseling. A pre-review of the report by key members in each EP reportedly made the EP conference more interactive and efficient, and thereby saved time. A total of 747 cases underwent CGP tests, 28 cases (3.7%) received genomically matched treatment, and 17 cases (2.3%) were referred for genetic counseling. Annotated reports for the simulated cases varied across the EPs, particularly the number of recommended IND trials, which seemed to be associated with the actual number of participants in IND trials.ConclusionsThis investigation provides reference data for the application of precision oncology in a clinical setting. Further investigations on the standardization of clinical annotations are warranted.
Journal Article
Effects of preoperative sagittal spinal imbalance on pain after lateral lumbar interbody fusion
2022
Sagittal misalignment has been associated with negative quality of life (QOL). However, there is no report on whether differences in preoperative sagittal misalignment in patients with lumbar degenerative diseases affect postoperative results after lateral lumbar interbody fusion (LLIF). We investigated whether preoperative sagittal alignment influences the correction of alignment after surgery and whether the preoperative sagittal alignment affects the rating of low back pain, leg pain, and leg numbness. The subjects were 81 patients (48 male, 33 females, average age at surgery 70.2 years) who underwent anterior–posterior combined surgery with LLIF and percutaneous pedicle screws from May 2018 to July 2020. Cluster analysis was performed using the preoperative sagittal vertical axis (SVA) value, and patients were classified into two groups (group 1; n = 30, SVA = 129.0 ± 53.4 mm, group 2; n = 51, SVA = 30.8 ± 23.5 mm). Baseline demographics and treatment data were compared between groups. Sagittal and pelvic parameters and pain scores, such as low back pain, leg pain, and leg numbness, were also compared. Operative time, blood loss, and length of hospital stay did not differ significantly between groups. The changes (Δ) in SVA and lumbar lordosis (LL) for all patients from before to after surgery were not significant (ΔSVA; p = 0.218, ΔLL; p = 0.189, respectively). The SVA, LL, and PI − LL changed significantly after the surgery in group 1, but no marked improvement in sagittal imbalance was obtained after LLIF surgery. The improvement in each pain score from before to after the surgery did not differ significantly between groups. LLIF surgery has a limited chance of recovering sagittal imbalance. However, postoperative low back pain, leg pain, and leg numbness may be improved by LLIF surgery, regardless of the preoperative sagittal alignment.
Journal Article
Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial
2024
Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2
+
) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2
+
gastric cancer. The primary cohort had 64% concordance between HER2 positivity and
HER2
(
ERBB2
) plasma gene amplification. Other key driver gene amplifications, specifically
MET
,
EGFR
and
FGFR2
, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with
HER2
gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.
Exploratory analyses of the DESTINY-Gastric01 trial show that baseline HER2-associated biomarkers in circulating tumor DNA or tissue samples were associated with therapeutic response in patients with HER2-positive tumors, and these analyses identify potential drivers of resistance.
Journal Article
The analysis of percutaneous pedicle screw technique with guide wire-less in lateral decubitus position following extreme lateral interbody fusion
2019
Background
Lateral lumbar interbody fusion (LLIF) and bilateral percutaneous pedicle fixation are valuable, minimally invasive lateral approaches used to treat symptomatic degenerative disc disease. In the current procedure, the patient’s position on the operating table is changed after LLIF surgery from the lateral decubitus to the prone position. The ability to perform both approaches with the patient in the same position should reduce operation time. Use of a guide wire is problematic during percutaneous pedicle screw (PPS) insertion using fluoroscopy with the patient in the lateral decubitus position. A new guide wire-less PPS system may solve this problem and reduce operation time. Here, we evaluated the operative data and efficacy for this technique.
Methods
This study included 30 patients (aged 70.8 ± 8.5 years; 17 men, 13 women) who underwent a combined operation (indirect decompression) using extreme lateral interbody fusion (XLIF) with only a single level for lumbar spinal canal stenosis and lumbar degenerative spondylolisthesis. Patient demographics and operative data were compared between two groups: patients who remained in the lateral decubitus position for pedicle screw fixation (L group) and those turned to the prone position (P group). Radiographic assessment was performed using pre- and postoperative anteroposterior and lateral lumbar films with measurement of lumbar lordosis, segmental lordosis, and segmental translation.
Results
We analyzed 18 patients in the P group and 12 in the L group. Age, sex, height, body weight, body mass index, estimated blood loss, and length of stay did not differ between groups. The operation time was 34 min shorter for the L group (P group 111.9 ± 25.0 vs. L group 77.5 ± 22.2 min,
p
< 0.01). Pre- and postoperative lordosis, segmental lordosis, and segmental translation did not differ significantly between groups.
Conclusions
A single position after XLIF surgery is a feasible modification to the standard procedure when used with fluoroscopy and a guide wire-less PPS system. The time saved is the main advantage of inserting the PPS with the patient in the lateral decubitus position without repositioning. Use of the lateral PPS with a guide wire-less technique may help improve operative efficiency and reduce cost.
Journal Article
Predicting proximal junctional failure in adult spinal deformity patients using machine learning models based on spinal alignment parameters
2025
Proximal junctional failure (PJF) is a significant mechanical complication following corrective surgery for adult spinal deformity (ASD), often resulting in structural failure at the uppermost instrumented vertebra and necessitating revision surgery. Early identification of patients at high risk for PJF remains clinically important but challenging due to the multifactorial and nonlinear nature of risk factors. This study aimed to evaluate the predictive performance of five machine learning (ML) models—Random Forest, Logistic Regression, Support Vector Machine (SVM), Decision Tree, and Naive Bayes—in identifying patients at risk for PJF using both preoperative and postoperative spinal alignment parameters. A retrospective cohort of 92 ASD patients who underwent two-stage corrective surgery, including lateral lumbar interbody fusion (LLIF), was analyzed. Radiographic parameters were measured preoperatively and approximately six weeks postoperatively. Six alignment-related features were selected through a combination of univariate statistical testing and Random Forest–based feature importance ranking: preoperative PI–LL, preoperative PT, postoperative PI–LL, postoperative and preoperative TK, and change in lumbar lordosis (ΔLL). Each ML model was trained and tested using five independent stratified 80:20 train-test splits. Among the models, Random Forest achieved the highest mean accuracy (78.4%) and area under the curve (AUC = 0.704). The predicted probabilities for PJF were significantly higher in the PJF group compared to non-PJF cases (0.306 ± 0.181 vs. 0.186 ± 0.164,
p
= 0.0057). Cross-validation confirmed model robustness (fivefold: 79.4%, tenfold: 77.3%). These findings suggest that Random Forest can serve as a reliable tool for preoperative and early postoperative PJF risk stratification based on alignment correction. Future work should incorporate bone mineral density, comorbidities, and multicenter validation to enhance clinical applicability.
Journal Article
The impact of the internationalization of political science on publishing in two languages: the case of Japan, 1971–2023
by
Nishikawa, Masaru
,
Sakai, Daisuke
,
Matsui, Akira
in
Academic careers
,
Authorship
,
Bibliometrics
2024
Recent advancements in bibliometrics have explored various academic dynamics like career peaks and citation impacts, with political science research highlighting gender disparities and co-authorship trends that vary by region. However, these studies often focus on Western contexts, missing contributions from non-Western regions, which underscores the need for expanding research to include multilingual publishing practices and diverse global perspectives to better understand the internationalization of the Social Sciences and Humanities. This study focuses on the internationalization trajectories of political science in Japan, specifically examining the publishing practices of Japanese political scientists in both English and Japanese. The study reveals a generational shift in which younger scientists, especially those working abroad, are increasingly publishing in English. This shift towards publishing in English contrasts with the practices of those working in Japan, who predominantly publish in Japanese and have not significantly adopted co-authorship. This article notes a decline in book publications in both English and Japanese among Japanese political scientists. This trend indicates a broader preference for peer-reviewed articles over books, driven by professional pressures in Japan. The study uses descriptive statistics, text analysis, network analysis, and qualitative analysis to explore these trends, highlighting the influence of internationalization on Japanese political science publication strategies.
Journal Article