Tokyo Medical University Hospital

Protein phosphorylation is a central post-translational modification regulating cellular signaling, frequently dysregulated in cancer. Mass spectrometry (MS)-based phosphoproteomics has emerged as a powerful approach to systematically profile phosphorylation events, thereby revealing aberrant kinase activity and therapeutic vulnerabilities that are not captured by genomic or transcriptomic analyses. Recent advances across the workflow-including optimized sample preparation and phosphopeptide enrichment, isotope- or label-free quantitative strategies, high-resolution mass spectrometry platforms, specialized algorithms for site identification and quantification, and integrative informatics analyses-have enabled the detection of tens of thousands of phosphorylation sites even from small clinical specimens. These developments have facilitated the characterization of signaling pathways across diverse cancer types, leading to the identification of targetable kinases and informing therapeutic strategies. In this review, we highlight studies that employed phosphoproteomic analyses of clinical specimens or patient-derived cancer cells to delineate signaling characteristics and to propose and validate therapeutic targets. Collectively, MS-based phosphoproteomics is poised to become a cornerstone of precision oncology. By enabling comprehensive and quantitative mapping of phosphorylation events, this technology allows mechanistic dissection of cancer signaling pathways and uncovers therapeutic vulnerabilities that may be exploited with targeted agents.

To carry out a preliminary study to evaluate the dose distribution variation between the analytical anisotropic algorithm (AAA) and the Boltzmann transport equation, and between point and volume prescriptions in three-dimensional conformal radiation for limited-stage small-cell lung cancer. We retrospectively selected patients with limited-stage small-cell lung cancer who received radiotherapy alone or chemoradiotherapy. Gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) were evaluated. Dose evaluation was performed for PTV, with AAA as point prescription, AAA as 50% prescription of PTV, Boltzmann transport equation as point prescription, and Boltzmann transport equation as 50% prescription of PTV. A total of 22 patients (15 males, 7 females; mean age=63.4 years) were included. The mean radiation doses for AAA/point AAA/D50, Boltzmann transport/point, and Boltzmann transport/D50 methods were 99.97±1.5%, 102.1±1.2%, 100.8±1.2%, and 101.3±1.3% to the GTV; 98.4±2.1%, 100.4±0.5%, 99.6±1.9%, 100.1±1.0% to the CTV; and 96.7±2.5%, 97.4±4.6%, 97.6±2.3%, 98.3±0.8% to the PTV, respectively. For AAA/point, AAA/D50, Boltzmann transport/point, and Boltzmann transport/D50 prescription methods, the correlation between the GTV (102.5±107.8 ml) and mean dose to the GTV was 0.23 (p=0.4), -0.476 (p=0.04), 0.00 (p=0.97), -0.79 (p<0.01); between CTV (342.7±242.6 ml) and mean dose to the CTV were 0.52 (p<0.01), -0.68 (p<0.01), 0.35 (p=015), -0.50 (p=0.03); between PTV (514.7±306.0 ml) and mean dose to the PTV were 0.59 (p<0.01) 0.75 (p<0.01),0.82 (p<0.01) and 0.78 (p<0.01), respectively. The AAA point-prescription approach can systematically underestimate target dose in 3D conformal radiotherapy for limited-stage small-cell lung cancer and shows less robust dose-volume behavior across GTV, CTV, and PTV compared with volume-based prescription and Boltzmann transport calculations. Therefore, AAA with point prescription should be avoided for dose calculation in this setting.

Anticoagulant effects of direct oral anticoagulants (DOACs) are influenced by their plasma levels and anti-factor Xa (FXa) activity. Delayed bleeding is a major adverse event associated with endoscopic mucosal resection (EMR) of colorectal neoplasms. However, the association between post-EMR bleeding and pharmacodynamics in patients taking DOAC remains unknown. This study investigated the association between pharmacological risk factors and delayed bleeding in patients receiving DOAC. This multicenter prospective trial in Japan evaluated the incidence of post-EMR delayed bleeding in DOAC users between April 2018 and May 2022 and determined the association of post-EMR delayed bleeding with plasma levels and FXa activity. The incidence of post-EMR delayed bleeding was 10.5% (95% confidence interval [CI]: 5.3%-18.0%). There were large individual differences in plasma levels and FXa activity for each DOAC. At the trough and Tmax, plasma DOAC levels and plasma level/dose ratios were significantly correlated with FXa activity. Multivariate analysis showed that high anticoagulant ability was a risk factor for post-EMR delayed bleeding (adjusted OR, 12.211; 95% CI: 1.081-137.922, p = 0.043). DOAC users with high anticoagulant activity may be at higher risk of post-EMR delayed bleeding from colorectal neoplasms.

Atmar's recent review highlights how vaccine clinical research networks have supported responses to emerging and pandemic pathogens and notes that public trust in vaccines is under threat [1].In this context, we observed that Japan has repeatedly experienced declines in vaccine uptake over decades, driven by policy shifts that followed public concern.Coronavirus 2019 (COVID-19) vaccination coverage among older adults in Japan was 54.4% in 2023 and fell to approximately 20% in 2024 [2,3].One reason for this decline is the shift in Japan's COVID-19 vaccination policy-harmonising with the surveillance downgrade in March 2024that involved reductions in financial subsidies and public awareness activities.

ObjectiveRehabilitation in the recovery phase for patients with brain tumors has not yet been fully established in clinical practice. With recent advances in molecular targeted therapies and device-based treatments, the need for functional recovery while continuing treatment after the acute phase has increased. In this report, we present three cases in which rehabilitation was implemented in our recovery-phase ward alongside temozolomide (TMZ), bevacizumab, or tumor treating fields (TTF). The aim is to explore the potential of recovery-phase care as a new option for brain tumor patients and to clarify the usefulness of rehabilitation interventions during ongoing treatment.MethodsThree patients with glioblastoma admitted to our recovery-phase ward were included. Case 1 received TMZ, Case 2 received bevacizumab, and Case 3 underwent TTF. All cases received physical, occupational, and speech therapy concurrently. Changes in physical function and activities of daily living (ADL) were evaluated.ResultsIn all cases, treatment continued without severe adverse events, and improvements in physical function and ADL were observed.Discussion and ConclusionThis report demonstrates that concurrent brain tumor treatment and rehabilitation can be achieved even in the recovery phase. By establishing a system that provides appropriate medical care and support after acute-phase treatment, safe and effective interventions in recovery-phase wards are possible. These findings suggest that such care may become a new standard role of recovery-phase medical services in the future.

Simple SummaryFailure to rescue (FTR)—death after major postoperative complications—is a persistent, variable problem in pancreatic cancer surgery. The review using PRISMA 2020 checklist and flow diagram screened 83 studies (1992–2025) and included 52 studies (2010–2025) across registry, multicenter, single-center, and audit designs. Due to heterogeneity in designs and FTR definitions (in-hospital, 30/90-day, severity- and complication-specific cases), a narrative synthesis was used; no formal risk-of-bias assessment or meta-analysis was performed. FTR varied by definition: pooled rates were 13.2% for 90-day CD ≥ III (G1); 10.3% for in-hospital/30-day CD ≥ III (G3); and 7.4% for 30-day “serious/major” morbidity (G8), with G1 > G3 (+3.0 pp; RR 1.29) and G3 > G8 (+2.9 pp; RR 1.39; all p < 0.001). Five domains were consistently linked to lower FTR and improved outcomes: (i) centralization to high-volume centers; (ii) evolution of surgical techniques; (iii) optimized perioperative management (early imaging, structured escalation); (iv) patient-specific risk stratification and prehabilitation; and (v) non-technical skills (NTS) including decision-making, situational awareness, communication, teamwork, and leadership. NTS measurement was infrequent, and no study assessed stress or fatigue management. Future work should standardize pancreas-specific FTR definitions, incorporate process-level rescue metrics, and embed NTS assessments with simulation and implementation science to change and strengthen team behaviors and reduce preventable patient mortality.Background: Failure to rescue (FTR), defined as death after major postoperative complications, is a critical quality indicator in pancreatic cancer surgery. Despite advances in surgical techniques and perioperative care, FTR rates remain high and vary across institutions. Methods: This systematic review uses a narrative synthesis followed by PRISMA 2020. A PubMed search (1992–2025) identified 83 studies; after screening, 52 studies (2010–2025) were included. Eligible designs were registry-based, multicenter, single-center, or prospective audits. Given substantial heterogeneity in study designs, FTR definitions, and outcome measures, a narrative synthesis was performed; no formal risk-of-bias assessment or meta-analysis was conducted. Results: Definitions of FTR varied (in-hospital, 30-day, 90-day, severity-based, and complication-specific cases). Reported rates differed by definition: average reported rates were 13.2% for 90-day CD ≥ III (G1); 10.3% for in-hospital/30-day CD ≥ III (G3); and 7.4% for 30-day “serious/major” morbidity (G8). Absolute differences were +3.0 and +2.9 percentage points (exploratory, descriptive comparisons). Five domains were consistently associated with lower FTR: (i) centralization to high-volume centers; (ii) safe adoption/refinement of surgical techniques; (iii) optimized perioperative management including early imaging and structured escalation pathways; (iv) patient-level risk stratification and prehabilitation; and (v) non-technical skills (NTSs) such as decision-making, situational awareness, communication, teamwork, and leadership. Among NTS domains, stress and fatigue management were not addressed in any included study. Limitations: Evidence is predominantly observational with substantial heterogeneity in study designs and FTR definitions; the search was limited to PubMed; and no formal risk-of-bias, publication-bias assessment, or meta-analysis was performed. Consequently, estimates and associations are descriptive/associative with limited certainty and generalizability. Conclusions: NTSs were rarely used or measured across the included studies, with validated instruments; quantitative assessment was uncommon, and no study evaluated stress or fatigue management. Reducing the FTR after pancreatic surgery will require standardized, pancreas-specific definitions of FTR, process-level rescue metrics, and deliberate strengthening of NTS. We recommend a pancreas-specific operational definition with an explicit numerator/denominator: numerator = all-cause mortality within 90 days of surgery; denominator = patients who experience major complications (Clavien–Dindo grade III–V, often labeled “CD ≥ 3”). Addressing the gaps in stress and fatigue management and embedding behavioral metrics into quality improvement programs are critical next steps to reduce preventable mortality after complex pancreatic cancer procedures.

今回、H. pylori未感染胃癌とH. pylori除菌長期後胃癌ついてまとめた。H. pylori未感染胃腫瘍は、①噴門部癌、②腺窩上皮型腫瘍（ラズベリー様、扁平隆起型）、③胃底腺型胃癌、胃底腺粘膜型胃癌、④印環細胞癌、⑤腸型・胃腸混合型分化型腺癌に大別される。噴門部腺癌の多くが進行癌であるのに対して、その他の領域の腫瘍は大部分がESDによる治療が可能である。部位，腺領域ごとの癌の好発部位と形態および組織型の特徴をふまえた観察が効率的な診断につながる。一方、H. pylori除菌後腫瘍に関しては、除菌が胃癌発症リスクを低下させるとともに胃がんを発症するリスクは、除菌前の胃粘膜萎縮の程度に応じて上昇するとされていたが、除菌後追跡期間が長くなるほど、除菌時の胃萎縮が軽度から中等度の患者でも未分化型胃癌の発生リスクが高くなるので要注意である。除菌後胃がんの内視鏡的特徴として、当初は、径は小さく、陥凹型が多いとされていたが、除菌後胃癌の表面に低悪性度異型上皮（ELA）が出現、さらにNBI拡大観察診断限界病変の存在など診断困難例の報告されている。胃癌発生のCorrea’s cascadeであるgastritis-atrophy-metaplasia-dysplasia-cancer sequence はH. pylori感染によりのみ進展すると考えられてきたが、。近年、細菌学領域における遺伝子解析が進歩し、H. pyloriと非H. pylori（口腔内細菌・常在菌など）の両者が胃炎から胃癌への進行に関与し、正常胃粘膜から活動性胃炎まではH. pylori dependent stage、萎縮性胃炎から胃癌まではH. pylori independent stageと考えられている。除菌後の胃発がんの進行に非H. pylori（口腔内細菌・常在菌）が関与していることが明らかであると報告されている。

Increased plasma levels of B-type natriuretic peptide (BNP) serve as a biomarker for heart failure (HF). This study aimed to develop a risk score to predict elevated BNP levels using traditional cardiovascular disease (CVD) risk factors. We analyzed data from 2809 Japanese individuals aged ≥ 40 years from the Suita Study, a population-based prospective cohort. All participants underwent follow-ups involving BNP measurements every two years. Developing BNP levels ≥ 100 pg/mL, a potential indicator of HF requiring treatment, was the outcome. Cox regression was applied to calculate hazard ratios for several CVD risk factors associated with developing BNP levels ≥ 100 pg/mL. Within a median follow-up period of 8 years, 339 participants developed BNP levels ≥ 100 pg/mL. The risk factors included older age, heavy smoking, former and heavy alcohol consumption, high blood pressure, estimated glomerular filtration rate < 45 mL/min/1.73 m2, CVD history, cardiac murmur, arrhythmia including atrial fibrillation, and left ventricular hypertrophy. The prediction model performed well in terms of discrimination (C-statistics = 0.750) and calibration (p-value for goodness-of-fit > 0.150). Our findings highlighted several CVD risk factors for BNP levels ≥ 100 pg/mL in the general Japanese population. Lifestyle modifications and regular health check-ups should be applied to reduce HF risk in vulnerable individuals.