Given the limited Japanese real-world evidence, this study aimed to evaluate the survival and safety of adjuvant nivolumab after neoadjuvant chemotherapy in patients with an incomplete pathological response to esophageal squamous cell carcinoma (ESCC).

This single-center retrospective study included 105 of 259 patients with ESCC who had an incomplete pathological response after neoadjuvant chemotherapy and esophagectomy. Recurrence patterns and immune-related adverse events (irAEs) were analyzed, and disease-free survival (DFS) and overall survival (OS) were compared between the nivolumab and non-nivolumab groups before and after propensity score matching (PSM).

Among 105 patients, 17 received adjuvant nivolumab. Median follow-up was 26.8 months; recurrence occurred in 33 patients (31.4%), and irAEs occurred in 2 nivolumab-treated patients (11.8%). Before PSM, OS and DFS were not significantly different between 2 groups. After PSM, OS remained nonsignificant (P = 0.202), whereas DFS showed a favorable trend toward improvement in the nivolumab group, with 1-year DFS rates of 75.0% versus 68.8% and 3-year DFS rates of 68.2% versus 19.3%, respectively (P = 0.067). Nivolumab was not an independent prognostic factor, although exploratory high-risk subgroups showed favorable DFS trends.

Adjuvant nivolumab showed a nonsignificant favorable trend in DFS after PSM, with late curve separation favoring the nivolumab group and manageable irAEs.

Dedicated service for Barrett's oesophagus (BO) surveillance may be more effective than conventional service, according to some single centre studies.

To determine whether the surveillance of BO through a dedicated service can improve key performance indicators (KPIs), and dysplasia detection rate (DDR) compared with conventional service in a multi centre study.

A retrospective cohort study was conducted across 6 NHS-hospitals, capturing BO surveillance data over 8 years. Factors associated with DDR were assessed by logistic regression.

There were 1037 dedicated and 976 conventional surveillance procedures (N = 2013), male: female ratio = 2.2:1; mean age = 64.4 (SD ± 12.2) years; mean maximum length of BO = 4.1 cm (range: 0-18 cm). All the KPIs and DDR were significantly higher in the dedicated service (DDR = 6.9%) than in the conventional service (DDR = 2.8%), p < 0.001. The use of narrow band imaging (NBI) and acetic acid chromoendoscopy (AAC) and sedation were high, and the complication rate was significantly lower in the dedicated service. The lesion recognition was significantly associated with DDR (OR = 6.9). Surprisingly, Seattle biopsy protocol adherence showed no correlation with DDR (OR = 0.47).

The dedicated service provides higher quality endoscopy, and a higher yield of early neoplasia. It uses more sedation, advanced imaging, and detects more lesions than conventional services. Thus, the dedicated surveillance could potentially replace time and cost consuming Seattle biopsies with targeted biopsies of visible lesions. In future, this may become easier with the use of artificial intelligence for lesion detection (CADe).

Active surveillance strategies have evolved to incorporate new technologies, such as MRI. However, trends in the adoption of this technology within the first year after cancer diagnosis as part of the initial active surveillance activity remain unclear.

Using SEER-Medicare data, this cross-sectional study examined trends in the use of various active surveillance strategies, including MRI associated biopsy, within the first year of cancer diagnosis among men diagnosed with localized prostate cancer between 2010-2011 and 2018-2019. Patients were stratified by Gleason score, age, and race/ethnicity.

Among patients without active treatment in the first year after localized prostate cancer diagnosis, the unadjusted proportion undergoing MRI associated biopsy as an active surveillance strategy increased from 0.8% in 2010-2011 to 3.16% in 2018-2019 for GS ≤ 6, and from 0.7% to 4.69% over the same period for GS ≥ 7. Patients aged 66-74 had consistently higher probabilities of undergoing MRI associated biopsy than patients aged 75+, and non-Hispanic White patients had consistently higher probabilities of undergoing MRI associated biopsy than non-Hispanic Black.

The use of new active surveillance strategies, such as MRI associated biopsy, were low in overall use but increased over time from 2010-2011 to 2018-2019, with notable differences across patient subgroups defined by age and race/ethnicity.

Avapritinib is a selective tyrosine kinase inhibitor approved for advanced PDGFRA exon 18-mutant gastrointestinal stromal tumors (GIST), including the imatinib-resistant D842V variant. However, its role in the preoperative setting for localized, resectable disease has not been defined.

We conducted a retrospective two-center exploratory case series of eight patients with localized, resectable PDGFRA-mutant gastric GIST who received preoperative avapritinib between 2020 and 2025. Radiographic and pathologic responses, treatment duration, adverse events (AEs), and surgical outcomes were evaluated.

All patients initiated avapritinib at 300 mg daily. Median treatment duration was 2 months (range, < 1-21 months). Tumor size decreased in seven patients (88%), with a median reduction of 25% and an overall range from -51% to +29%. Three patients (38%) met RECIST-based thresholds for partial response (≥ 30% reduction). Five patients underwent surgical resection, all achieving complete (0% viable tumor) or near-complete (≤ 5% viable tumor) pathologic response. Dose reductions were required in three patients due to toxicity; however, tumor regression continued in all. Treatment-related grade ≥ 3 AEs occurred in 50% of patients, including one fatal intracranial hemorrhage. Most toxicities emerged within two months, and most nonfatal toxicities improved with dose adjustment or discontinuation.

In this exploratory two-center case series, preoperative avapritinib demonstrated marked pathologic activity in localized PDGFRA-mutant GIST, including after dose reduction in some patients. However, early toxicity at the standard 300 mg dose was frequent and, in several cases, prevented patients from reaching planned surgery. These findings argue against routine preoperative avapritinib use and support limiting this approach to clinical trials or highly selected patients with a compelling surgical rationale until prospective data are available.

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that hijack the ubiquitin-proteasome system to drive catalytic, sub-stoichiometric degradation of disease-associated proteins, offering a mechanistic advantage over occupancy-driven inhibitors and access to 'undruggable' targets. However, their clinical translation is constrained by high molecular weight, poor solubility, low oral bioavailability, inefficient membrane permeability, nonspecific biodistribution, off-target degradation, and the concentration-dependent 'hook effect.' Exosomes, nanoscale extracellular vesicles with innate biocompatibility, low immunogenicity, prolonged circulation, and the ability to cross barriers such as the blood-brain barrier, offer a biologically integrated platform to overcome these limitations. This review traces the evolution of PROTAC technology, delineates the challenges of conventional delivery, and evaluates the rationale for exosomal encapsulation, including cargo protection, intracellular trafficking, endosomal escape, and release kinetics. We examine natural and engineered exosomes spanning source selection, active loading strategies, and surface functionalization for tissue-specific homing and synthesize therapeutic applications across viral infections, cancer, neurodegenerative disorders, and inflammatory diseases. Proof-of-concept studies, such as camel milk-derived exosomes delivering the BRD4-targeting PROTAC ARV-825, demonstrate enhanced permeability, lower IC₅₀ values, and improved oral bioavailability. Finally, we discuss key hurdles to clinical translation: scalable production, purification, and standardization, and outline future directions for exosome-mediated targeted protein degradation.

Scalable, non-invasive tools are critically needed to improve early lung cancer detection and optimize primary care referral pathways. We evaluated Inflammacheck, a point-of-care device utilizing exhaled breath condensate (EBC) H₂O₂ and physiological parameters with machine learning for non-invasive lung cancer detection in a real-world screening population. Exhaled Hydrogen Peroxide for Early Lung Cancer Detection (ExPeL) study participants, from the UK Targeted Lung Health Check (TLHC) programme, included individuals with suspected lung cancer and low-risk ever-smoker controls. EBC was collected via Inflammacheck, measuring H₂O₂, end-tidal CO₂, humidity, temperature, and exhalation flow rate. Multivariate analyses (PCA, LDA and Mahalanobis distance) assessed intrinsic group separation. SMOTE-balanced data trained supervised machine learning models (stacked and voting ensembles), which were then evaluated on held-out test sets. In parallel, untargeted LC-MS metabolomics was performed to identify discriminatory molecular features. Analyzing 34 participants with valid EBC data, 83% of cancer cases were early-stage (I-II), reflecting a screening population. Multivariate analysis clearly separated lung cancer and controls across PCA, LDA, and Mahalanobis mapping. The voting ensemble model achieved: Accuracy 85.7%, Sensitivity 80%, Specificity 100%, Precision (PPV) 100%, ROC-AUC 0.90 and MCC 0.73. Crucially, no false positives were identified. EBC variables revealed greater dispersion in cancer patients, reflecting physiological heterogeneity missed by univariate analysis. Untargeted metabolomics identified 2132 features, with four key metabolites yielding an AUC of 0.969 for cancer discrimination. Inflammacheck effectively distinguishes early-stage lung cancer via a rapid, non-invasive breath test, findings which are highly relevant for primary care and screening triage, where non-specific symptoms and low prevalence pose challenges.

The trends and contributors of racial and ethnic disparities in causes of death among patients with clear cell renal cell carcinoma remain unclear. We analyse SEER data (2000-2019) and find that Black patients have the highest 5-year cumulative incidence of death (22.4% vs. 21.7% in whites). Despite a decreasing trend in mortality, the disparities persist between Black and white people (HR 1.15, 95% CI 1.09-1.22) and between AIAN and white people (1.25, 1.10-1.43). Disparities in death from cardiovascular disease between Black and white people increase over time. Stage at diagnosis, receipt of surgery, income, and geographic factors partially explain the observed disparities in mortality patterns. This study identifies specific, measurable contributors to mortality disparities, suggesting that interventions targeting earlier detection, equitable treatment, and socioeconomic barriers are needed.

Robotic gastrectomy has been adopted for gastric cancer. However, operative time remains longer than that of laparoscopic surgery. Junk time has been proposed as a major contributor to prolonged operative duration. This study evaluated intraoperative time structure during the initial clinical experience with the minimally invasive laparoscopic and robotic (MILAR) approach using the da Vinci SP system.

This retrospective exploratory workflow analysis included consecutive patients who underwent robot-assisted distal gastrectomy with D1+/D2 lymphadenectomy between May 2024 and June 2025. Patients were divided into the SP (MILAR) group and the conventional multi-port robotic (Xi) group. Operative videos from skin incision to gastric transection were reviewed to quantify effective time and junk time.

A total of 40 patients were analyzed (SP, n = 11; Xi, n = 29). Total operative time was significantly shorter in the SP group than in the Xi group (148.0 vs. 204.0 min, p = 0.001). Junk time was significantly reduced (30.4 vs. 36.6 min, p = 0.034), accompanied by fewer robotic instrument exchanges (4 vs. 46, p < 0.001). Effective time was shorter in the SP group; although this finding may have been influenced by surgeon expertise and case complexity. No increase in procedure-related complications was observed in the SP group.

The present exploratory study describes differences in intraoperative time structure observed during the initial clinical experience with the MILAR approach using SP system. These findings provide insight into workflow characteristics of a hybrid team-based approach and warrant further evaluation in prospective studies.

Glioblastoma (GBM) remains one of the most aggressive primary brain tumors, with poor prognosis, high recurrence, and limited therapeutic options. Although substantial progress has been made in drug development, effective clinical translation is still constrained by inefficient delivery across the blood brain barrier (BBB) and blood brain tumor barrier (BBTB), insufficient tumor accumulation, intratumoral heterogeneity, acquired therapeutic resistance, and dose limiting systemic toxicity. Nanomedicine offers a promising strategy to address these barriers through tunable physicochemical properties, flexible surface functionalization, improved pharmacokinetics, and controllable drug release. In this review, we systematically summarize recent advances in nanomedicine enabled GBM therapy from four interrelated perspectives: the optimization of nanomaterial properties, the development of goal-oriented targeting strategies, the rationalization of delivery routes, and the engineering of smart stimuli-responsive nano-systems. Rather than only cataloguing representative nanoplatforms, we emphasize how material parameters, biological targeting mechanisms, delivery routes, and release behaviors are mechanistically linked to BBB or BBTB penetration, tumor accumulation, therapeutic efficacy, and translational feasibility. Importantly, we also incorporate a key failure case analysis of representative clinical and preclinical studies, highlighting why promising nanotherapeutic concepts may fail because of inadequate intratumoral distribution, insufficient survival benefit, poor patient selection, manufacturing complexity, safety concerns, or impractical trial design. By integrating delivery mechanisms, cross platform comparison, translational barriers, and future optimization principles, this review provides a critical and forward looking framework for the rational design of precise, effective, and clinically translatable nanomedicine strategies for GBM treatment.

Lymphadenectomy around the left recurrent laryngeal nerve is one of the most technically demanding steps in esophagectomy. Even in robot-assisted esophagectomy, the operative field easily becomes wet and achieving on-demand suction remains challenging.

Between July 2024 and November 2025, 11 patients underwent robot-assisted esophagectomy in the prone position. We developed a simple on-demand suction technique by suturing gauze to a commercially available suction tube, allowing both the surgeon and the assistant to perform suction as needed. The modified tube can be manipulated using either robotic instruments or assistant forceps and can also be used for gentle tracheal rolling during lymphadenectomy. Furthermore, to evaluate the feasibility and safety of this technique, we conducted a retrospective comparison with 11 cases performed using the conventional method (tracheal traction with a robotic Cadiere forceps) between March 2023 and May 2024. All procedures were performed by a single surgeon.

This simple and low-cost technique facilitates maintenance of a dry operative field during robot-assisted esophagectomy. Furthermore, in comparison with the conventional method, no significant differences were observed in operative time, blood loss, or the incidence of recurrent laryngeal nerve palsy; however, there was a trend toward reduced intraoperative manipulation time. These findings suggest that this technique offers comparable safety to the conventional approach while potentially contributing to improved operative field management.