A drug-coated balloon (DCB) strategy has become an established option for de novo coronary lesions, offering the advantage of avoiding permanent implants. However, very long-term vascular changes after stentless percutaneous coronary intervention (PCI) remain insufficiently characterized. We report a case of chronic total occlusion that developed eight years after DCB angioplasty for a diffuse long right coronary artery lesion in a patient with unstable angina. A 65-year-old man developed exertional chest discomfort approximately seven years after the index procedure, and cardiac computed tomography demonstrated severe calcification and suspected occlusion of the previously treated segment. At the index procedure, we selected a DCB-only strategy because intravascular ultrasound (IVUS) revealed a long, diffuse lesion requiring multiple stents and extensive drug-eluting stent (DES) implantation carries increased long-term risks. During repeat PCI, IVUS demonstrated dense calcification and high-echoic crescentic neointimal tissue without imaging features suggestive of thrombus. The imaging findings suggested atherosclerotic progression, potentially compounded by the limited acute luminal gain achieved at the index procedure, the cumulative burden of cardiovascular risk factors, and chronic inflammatory cell infiltration. Although the pharmacological effect of paclitaxel diminishes within months, preclinical studies have suggested that low residual tissue concentrations might contribute to late fibrotic or calcific remodeling. Device-related neoatherosclerosis appears unlikely because of the absence of a metallic scaffold. This case illustrates the multifactorial nature of very late vascular changes after stentless PCI and demonstrates how multimodality imaging, including cardiac computed tomography and IVUS, can describe late lesion morphology and healing patterns. The findings highlight the complex late-phase vascular morphology that may emerge in patients with diffuse disease and multiple risk factors and underscore the clinical value of comprehensive imaging assessment at very late follow-up.

Dermatomyositis is a recognised paraneoplastic inflammatory myopathy although its association with oesophageal malignancy is uncommon. Most reported cases either precede or accompany the initial diagnosis of malignancy. We report a man in his late fifties with previously treated oesophageal squamous cell carcinoma who developed florid dermatomyositis after approximately 6 years of sustained remission following chemotherapy, radiotherapy and pembrolizumab therapy. He presented with progressive proximal muscle weakness, dysphagia and characteristic cutaneous manifestations accompanied by markedly elevated creatine kinase levels. Fluorodeoxyglucose positron emission tomography-CT demonstrated metastatic oesophageal squamous cell carcinoma involving the thoracic oesophagus, abdominal lymph nodes and liver. Corticosteroids followed by paclitaxel-carboplatin rechallenge chemotherapy resulted in marked improvement in both inflammatory manifestations and tumour burden. The chronology was notable for parallel evolution of inflammatory activity and metastatic disease after prolonged oncological remission.

Paclitaxel (PTX) is a potent chemotherapeutic agent for solid malignancies. However, its poor aqueous solubility necessitates toxic solubilizers in conventional formulations, which lead to adverse reactions and unpredictable pharmacokinetics. Liposomal encapsulation offers a biocompatible alternative to overcome these limitations. In this study, a sensitive ultrafiltration coupled with ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of free and total PTX in biological samples. This method was applied to compare the pharmacokinetic behavior of liposomal PTX (PTX-Lip) and conventional PTX injection in rats. Despite receiving a double dose (10 mg/kg), rats treated with PTX-Lip exhibited significantly lower dose-normalized initial concentration (C0/Dose) and systemic exposure (AUC(0-∞)/Dose) along with a prolonged elimination half-life (t1/2) compared with the conventional formulation (5 mg/kg), indicating sustained release. Tissue distribution studies revealed extensive and persistent accumulation of PTX-Lip in the spleen and liver, consistent with reticuloendothelial system uptake, whereas distribution to other tissues was reduced. Excretion profiling demonstrated a fundamental shift in clearance pathways, from combined renal/hepatobiliary elimination for conventional PTX to predominantly hepatobiliary fecal excretion for PTX-Lip, with cumulative fecal recovery reaching 39.27% of the dose, a 2.4-fold increase over the conventional group (16.50%). Collectively, these findings illustrate how liposomal encapsulation modifies the in vivo disposition of PTX through reticuloendothelial system-mediated sequestration, controlled drug release, and rerouted elimination. These descriptive observations, generated in healthy rats without pharmacodynamic or efficacy endpoints, provide a pharmacokinetic reference for the rational design of liposomal nanomedicines. However, these findings should be interpreted as a baseline pharmacokinetic characterization rather than as evidence of therapeutic benefit, and they are intended to generate hypotheses for validation in appropriate disease models with efficacy and safety endpoints. SIGNIFICANT STATEMENT: This study established an ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of free and total paclitaxel and provided a descriptive characterization of formulation-associated differences in pharmacokinetics, tissue distribution, and excretion. These findings offer a pharmacokinetic reference that may inform the rational design and evaluation of lipid-based nanomedicines in future studies.

Background The chemoradiotherapy for oesophageal cancer followed by surgery study (CROSS) protocol, combining neoadjuvant chemoradiotherapy with surgical resection, is the standard of care for patients with locally advanced oesophageal cancer. Real-world patients often don't meet CROSS trial criteria. We evaluated if the trial's positive results apply to patients with large, ineligible lesions. Materials & methods In this retrospective analysis, we included patients with oesophageal cancer treated between November 2022 and November 2025 who received neoadjuvant chemotherapy plus radiotherapy (NACT+RT) at a dose of 41.4 Gray (Gy) delivered in 23 fractions, with concurrent weekly paclitaxel and carboplatin, followed by surgical resection. For study purposes, patients were divided into two groups according to whether they met the CROSS-eligibility criteria. The CROSS-ineligibility criteria were defined as patients with any of the following clinical features, i.e., T4a disease, tumor length >8 cm, or planning target volume length >16 cm. Result Out of 65 cases, 69.2% (n=45) of patients were CROSS-ineligible. Fifty-one cases completed the intended treatment of neoadjuvant chemoradiation followed by surgery. The pathological complete response (pCR) rate was 58.8% (n=30) in the total cohort population (n=51) who underwent NACT+RT followed by surgery. Out of 36 CROSS-ineligible patients, 55.6% (n=20) had a pCR compared to 66.6% (n=10) in CROSS-eligible cases (n=15). Fourteen patients did not undergo surgery after NACT+RT. At a median follow-up of 17 months, the one- and two-year progression-free survival (PFS) rates for the entire cohort were 80% and 68%, respectively. The one-year PFS rate was 90% for CROSS-eligible cases (n=20) versus 80% (p=0.7) for CROSS-ineligible cases (n=45). Similar rates for two-year PFS were 54% and 62% (p=0.7) for CROSS-eligible and CROSS-ineligible cases, respectively. In a subset analysis of the patients who underwent surgery (n=51), the one-year PFS rates were 93% versus 90% (p=0.75) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. Similarly, the two-year PFS rates were 43% versus 70% (p=0.75) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. The one- and two-year overall survival (OS) rates for the entire cohort were 93% and 77%, respectively. The one-year OS rates were 95% for CROSS-eligible cases (n=20) versus 93% (p=0.8) for CROSS-ineligible cases (n=45). Similar rates for two-year OS were 54% and 72% (p=0.8) for CROSS-eligible and CROSS-ineligible cases, respectively. In a subset analysis of patients who underwent surgery (n=51), the one-year OS rates were 93% versus 92% (p=0.78) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. Similarly, the two-year OS rates were 43% versus 70% (p=0.78) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. Conclusion With proper patient selection, the CROSS regimen can be safely extended to CROSS-ineligible patients, demonstrating its safety without compromising survival. We propose that oesophageal cancers presenting with cT4a tumours, tumours measuring greater than 8 cm, and nodal stages N2 and N3 can be safely treated with neoadjuvant chemoradiotherapy followed by surgery, a finding that warrants confirmation in larger prospective studies.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have provided significant clinical benefit to patients with EGFR-mutant non-small cell lung cancer (NSCLC), but multiple concurrent genetic alterations may limit their efficacy. We report a case of advanced lung adenocarcinoma harboring concurrent EGFR exon 19 deletion, ERBB2 amplification, and ERBB2 p.S310F mutation. The patient experienced disease progression after multiple lines of therapy, including osimertinib-based treatment, pemetrexed/carboplatin plus ivonescimab, and nab-paclitaxel plus Endostar. Considering that primary ERBB2 genetic alterations might contribute to the limited benefit from EGFR-TKI-based therapy, the patient subsequently received trastuzumab rezetecan monotherapy. After four cycles of treatment, the patient achieved a partial response in pulmonary lesions and a complete response in intracranial metastases. This case indicates that trastuzumab rezetecan may be a promising treatment option for EGFR-mutant NSCLC with concurrent ERBB2 genetic alterations, even after failure of multiple lines of treatment.

The development of effective small interfering RNA (siRNA) therapeutics for pancreatic ductal adenocarcinoma (PDAC) is severely hindered by formidable physiological barriers restricting systemic stability. To address these critical challenges, we developed an advanced actively targeted drug delivery system (DDS) utilizing a novel regioisomer of a folic acid-conjugated L-2,4-diaminobutyric acid octamer (FA-Dab8α) complexed with strategically chemically modified siRNA targeting the oncogenic small nucleolar RNA SNORA22. Although SNORA22 represents a potent therapeutic target for suppressing PDAC invasion and metastasis, achieving robust in vivo efficacy requires highly optimized delivery vehicles. In this study, we systematically evaluated the structural impacts of ligand conjugation, demonstrating that the α-regioisomer (FA-Dab8α) spontaneously optimizes polyplex packing to achieve remarkably superior cellular uptake, lysosomal trafficking, and target gene knockdown over its γ-counterpart. Furthermore, the strategic incorporation of phosphorothioate linkages and 2'-O-methyl modifications conferred exceptional RNase resistance, maintaining payload stability within the bloodstream. The therapeutic potential of this optimized platform was evaluated in a clinically relevant preclinical mouse model established with human PDAC cell line-derived organoids. Systemic administration of the SNORA22 siRNA-FA-Dab8α complex resulted in profound tumor accumulation within 24 h and induced unprecedented tumor growth inhibition that significantly outperformed the clinical standard chemotherapy, gemcitabine plus paclitaxel (GP). Histopathological analysis revealed marked tumor necrosis and a drastic reduction in surrounding tissue infiltration, with zero detectable systemic toxicity in vital organs. These findings demonstrate that the precise structural optimization of ligand-modified oligopeptide carriers enables highly efficient oligonucleotide delivery, establishing the SNORA22 siRNA-FA-Dab8α complex as a powerful and highly promising clinical strategy for refractory pancreatic cancer.

Zabilugene almadenorepvec (VCN-01) is a hyaluronidase-expressing oncolytic adenovirus with a favorable safety profile and encouraging antitumor activity in patients with pancreatic ductal adenocarcinoma. This randomized phase 2b trial evaluated the efficacy and safety of two doses of intravenous VCN-01 with gemcitabine and nab-paclitaxel (GnP) versus GnP alone as first-line therapy in metastatic pancreatic ductal adenocarcinoma. The primary endpoints were overall survival (OS) in the intent-to-treat and full analysis set (FAS) populations, and safety and tolerability in the safety population. In the intent-to-treat population (VCN-01 + GnP, n = 53; GnP, n = 48), median OS in the VCN-01 + GnP versus GnP group was 10.6 versus 8.6 months (hazard ratio (HR) = 0.69 (95% confidence interval (CI) 0.42-1.12), P = 0.196) and progression-free survival was 5.6 versus 4.6 months (HR = 0.63 (95% CI 0.4-1.00), P = 0.046). In the FAS population (n = 48 per group), median OS was 10.8 months in the VCN-01 + GnP group versus 8.6 months in the GnP group (HR = 0.57 (95% CI 0.34-0.96), P = 0.055) and progression-free survival was 7.0 versus 4.6 months (HR = 0.55 (95% CI, 0.34-0.88), P = 0.011). The primary efficacy endpoint of OS was met in the FAS population. Duration of response was 11.2 versus 5.4 months (HR = 0.22 (95% CI 0.08-0.63), P = 0.004). No statistically significant differences were observed in overall response rate, disease control rate or carbohydrate antigen 19-9 levels between treatment groups. In addition, survival rates in the VCN-01 + GnP group versus the GnP group were 35.5% versus 12.8% at 15 months, and 31.1% versus 8.5% at 18 months. Patients receiving two VCN-01 doses 14 weeks apart showed greater survival benefit, with sustained circulating viral genomes indicating ongoing viral replication and preserved second-dose bioactivity despite persistent neutralizing antibodies. More frequent VCN-01-related events included pyrexia, flu-like symptoms, elevation in liver enzymes and decreases in platelet counts, with serious events occurring in 22.6% of patients. Milder toxicity was observed after the second administration. Two fatal events occurred, one in each treatment group; neither was considered related to study treatment. These results further support VCN-01 combined with GnP as a first-line therapy for metastatic pancreatic ductal adenocarcinoma and warrant evaluation in a blinded phase 3 trial. ClinicalTrials.gov identifier: NCT05673811 .