NTT Medical Center

Metastatic colorectal cancer (mCRC) differs clinically based on RAS and BRAF mutations or DNA methylation. However, in mCRC, the prognostic value and biological characteristics of genome-wide DNA methylation status (GWMS) in each RAS/BRAF genotype is unknown. To clarify this, primary tumor samples from patients with informed consent in the phase III TRICOLORE study were collected, and RAS and BRAF mutations, immunohistochemical staining of mismatch repair-related proteins, comprehensive gene expression, and genome-wide DNA methylation were analyzed. The tumor samples were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Gene set enrichment analysis (GSEA) was conducted using microarray data. A total of 226 patients were included and classified into the RAS/BRAF wild-type (wt) (n = 125), RAS mutant (mt) (n = 87), and BRAF mt (n = 14), of whom 22 (17.6%), 30 (34.5%), and 14 (100%) had HMCC. HMCC exhibited significantly worse overall survival (OS) than that of LMCC in the RAS/BRAF wt group but not in the RAS mt group. In GSEA, RAS/BRAF wt HMCC was associated with microsatellite instability and BRAF V600E mutation. The poor prognosis of RAS/BRAF wt HMCC may be attributed to gene expression patterns associated with microsatellite instability and BRAF V600E mutation.

This report describes a rare case of irreducible closed volar subluxation of the distal interphalangeal (DIP) joint of the small finger following a sports injury. Closed reduction failed, leading to open surgery, which revealed ulnar condyle entrapment between a partially torn extensor tendon and volarly displaced oblique retinacular ligament (ORL). Flexing the proximal interphalangeal (PIP) joint to 90° while extending the DIP joint relaxed the ORL, enabling dorsal repositioning and successful reduction. Awareness of this mechanism may help hand surgeons achieve effective reduction. Level of Evidence: Level V (Therapeutic).

Background and Objective: Recently developed immune checkpoint inhibitors (ICIs) have demonstrated a strong anti-tumor effect when used with cytotoxic chemotherapy agents. Consequently, a significant proportion of stage III–IV inoperable advanced lung cancers have been downstaged, and a few select patients have undergone salvage surgery to resect loco-regional residual or regrowth tumors. However, those surgical outcomes are not clarified due to the rarity. In this narrative review, we summarize the clinical features and postoperative outcomes of salvage surgery for advanced-stage lung cancer after ICI treatment. Methods: On August 1, 2025, we searched PubMed for cases published between January 2019 and June 2025, using the search terms “salvage lung cancer surgery and/or immune checkpoint inhibitor” or “salvage lung cancer surgery and/or immunotherapy”. We included case presentations or original manuscripts from English literature and excluded review articles, surgeries for biopsy, incomplete resections and non-pulmonary resections. We defined “salvage surgery” as surgery for patients with initially unresectable advanced-stage lung cancer, where the residual downstaged tumor lesions or recurrent cancer lesions are resected after chemotherapy or chemoradiotherapy with an ICI, such as pembrolizumab, durvalumab, nivolumab or atezolizumab. Key Content and Findings: We found 101 articles, from which we selected 46 patients. The median age was 64 years old (range, 44–82 years old). The histology was adenocarcinoma (18 cases), squamous cell carcinoma (22 cases), large cell carcinoma (2 cases), adenosquamous cell carcinoma (1 case), and other (3 cases). The pretreatment clinical stage was III (27 cases) and IV (19 cases). The postoperative complications (all grade) occurred in 13 out of 46 cases, and the 30-day mortality was 1 out of 46 cases. The chemotherapy response rate was 9 out of 25 cases for a pathological complete response. The postoperative pathological stage distribution was ypStage 0/I/II/III/IV/NA: 9/17/8/7/3/2. Documented postoperative survival time ranged from 1 to 43 months. Conclusions: Salvage lung resection after treatment with an ICI for initially unresectable lung cancer is a feasible and acceptable procedure, based on perioperative surgical results. However, close, optimal patient selection with a multidisciplinary team and cautious perioperative management are required. Further long-term follow-up data is expected.

Durable outcomes with neurovascular stents require balancing antithrombotic performance with rapid endothelialization. We previously developed an amine-functionalized surface modification (Anti-thrombus formation, Endothelial-growth promotion, tissue Integration, and Surface; AEGiS Technology) with antithrombotic behavior. In this study we evaluated its pro-endothelialization properties and explore the mechanism. Adsorption of extracellular matrix proteins from human plasma was profiled on AEGiS-modified versus control NiTi surfaces with an a priori focus on vitronectin. Human umbilical vein endothelial cell (HUVEC) adhesion was quantified by attached cell numbers and post-wash retention as a measure of adhesion strength. Migration and surface coverage were assessed in an in vitro endothelialization model designed to mimic stents on vessel walls. For translation, self-expanding stents bearing AEGiS or control coatings were deployed in a porcine model and endothelial coverage at 1 week was quantified by angiography and histology. The AEGiS surface selectively increased vitronectin adsorption compared with the control surface. Consistent with this shift, AEGiS supported greater HUVEC adhesion and stronger retention. In the endothelialization model, AEGiS accelerated coverage of the substrate compared with the control. In vivo, AEGiS-modified stents showed greater endothelial coverage at 1 week than control stents. Amine functionalization enriched vitronectin adsorption and supported early endothelial coverage, indicating its potential to promote endothelialization of neurovascular stents.

IntroductionPain perception greatly varies among individuals and represents a major clinical challenge. Current pain assessment relies on subjective reports; although straightforward, these cannot distinguish the diverse underlying pathophysiological mechanisms of pain. Elucidating brain functional mechanisms using fMRI is crucial for realizing more objective pain assessment. Most studies have focused on thermal stimuli or psychological evaluations, and no studies have focused on differences in sensitivity to mechanical stimulation. Therefore, in this study, we aimed to identify regional differences in brain activation during mechanical stimulation at different intensities using fMRI and to clarify brain activation patterns associated with differences in pain sensitivity between the low- and high-threshold groups.MethodsWe enrolled 52 healthy adults. After measuring mechanical tactile and pain thresholds, fMRI was performed during mechanical stimulation at three intensities (60, 100, and 180 g). Regions of brain activation were identified for each stimulus intensity in all participants and for the high- and low-threshold groups, using the 100-g stimulus as the cutoff value, based on mechanical pain thresholds.ResultsNotable results regarding the change in stimulus intensity are that significant activation was observed in the anterior insular cortex at 60 g; anterior insular cortex, precentral gyrus, and cerebellum at 100 g; and cerebellum, angular gyrus, and thalamus at 180 g of stimulus intensity. Notable results regarding the level of pain sensitivity are that, when classified into the low- (n = 24) and high-threshold (n = 28) groups, activation in the low-threshold group was limited to the somatosensory cortex and its related regions. However, the high-threshold group exhibited activation in the anterior insular cortex, superior parietal lobule, precentral gyrus, and middle frontal gyrus, in addition to the somatosensory cortex.ConclusionThe expansion of brain activation with increasing stimulus intensity suggests the involvement of higher-order central processing, such as attention and response preparation, in noxious stimulus processing. Additionally, differences in pain thresholds may reflect variations in the mode of neural response; the high-threshold group exhibited activation in the frontoparietal network, associated with cognitive control. These findings provide a neurobiological basis for psychological interventions and may serve as a foundation for developing objective biomarkers and advancing personalized pain treatment strategies.

Gastric adenoma and cancer are common in Asia, with early detection critical for prognosis. Synchronous multiple early gastric cancers (SMEGCs) occur in 6% to 14% of cases, but their clinicopathological characteristics remain unclear. This study analyzed synchronous multiple gastric neoplasms treated by endoscopic resection or surgery to aid early detection. Among 2,991 cases of early gastric cancer or adenoma diagnosed at our institution, 173 patients with 346 synchronous lesions (January 2016-March 2024) were analyzed. All lesions were mucosal or submucosal. Lesions were categorized as "1st" (larger) and "2nd" (smaller), and clinicopathological characteristics were compared using Chi-square and Fisher's exact tests with Cramér's V. Patients had a mean age of 73.2 years; 72.8% were male. Most lesions were in the lower/middle stomach, differentiated (92.2%), depressed (52.9%), and brownish on narrow-band imaging (65.3%). Mean tumor diameter was 13.4 mm. Although 1st lesions were larger, other features showed high concordance (≥ 0.25 Cramér's V) in location, morphology, histology, invasion depth, and coloration. Survival was 94.8% (nine unrelated deaths). Synchronous multiple gastric neoplasms tend to have similar endoscopic and histopathologic features and often occur within the same belt-like region along the short axis of the stomach. This pattern was named boundary equal lesions trends (BELT). When detecting one lesion, considering BELT is essential.

IntroductionBone-modifying agents (BMAs) effectively prevent skeletal-related events (SREs) in bone metastases (BMs). While early BMA use is recommended upon BM diagnosis, its benefits and optimal timing remain unclear. This study investigated whether early BMA initiation after BM diagnosis delays SRE onset by analyzing pooled data from placebo-controlled trials.MethodsRandomized controlled trials in which a BMA or placebo was administered after BM diagnosis were extracted. For each trial's BMA and placebo arms, the waiting period from BM diagnosis to BMA initiation and the effective period from BMA initiation to SRE onset were investigated. The hazard ratio (HR) for the SRE-free period relative to the placebo period was calculated. A waiting period of ≤6 months was defined as the early initiation group, whereas that of >6 months was the delayed initiation group. The HRs were meta-analyzed.ResultsData from 17 studies were analyzed. Early initiation of BMAs showed a trend toward a longer duration of efficacy compared with delayed initiation (+5.5 versus [vs.] + 3.2 months, p = 0.056). However, the pooled HR demonstrated efficacy at both initiation timepoints (0.62 [0.56-0.69] vs. 0.73 [0.60-0.83]).ConclusionsAlthough early initiation of a BMA after BM diagnosis is recommended, its efficacy-specifically whether it prolongs the time to SRE onset-remains unclear.