MRI Features for Predicting Microvascular Invasion and Postoperative Recurrence in Hepatocellular Carcinoma Without Peritumoral Hypointensity.

Purpose: To identify MRI features of hepatocellular carcinoma (HCC) that predict microvascular invasion (MVI) and postoperative intrahepatic recurrence in patients without peritumoral hepatobiliary phase (HBP) hypointensity. Patients and Methods: One hundred and thirty patients with HCC who underwent preoperative gadoxetate-enhanced MRI and curative hepatic resection were retrospectively reviewed. Two radiologists reviewed all preoperative MR images and assessed the radiological features of HCCs. The ability of peritumoral HBP hypointensity to identify MVI and intrahepatic recurrence was analyzed. We then assessed the MRI features of HCC that predicted the MVI and intrahepatic recurrence-free survival (RFS) in the subgroup without peritumoral HBP hypointensity. Finally, a two-step flowchart was constructed to assist in clinical decision-making. Results: Peritumoral HBP hypointensity (odds ratio, 3.019; 95% confidence interval: 1.071-8.512; P=0.037) was an independent predictor of MVI. The sensitivity, specificity, positive predictive value, negative predictive value, and AUROC of peritumoral HBP hypointensity in predicting MVI were 23.80%, 91.04%, 71.23%, 55.96%, and 0.574, respectively. Intrahepatic RFS was significantly shorter in patients with peritumoral HBP hypointensity (P<0.001). In patients without peritumoral HBP hypointensity, the only significant difference between MVI-positive and MVI-negative HCCs was the presence of a radiological capsule (P=0.038). Satellite nodule was an independent risk factor for intrahepatic RFS (hazard ratio,3.324; 95% CI: 1.733-6.378; P<0.001). The high-risk HCC detection rate was significantly higher when using the two-step flowchart that incorporated peritumoral HBP hypointensity and satellite nodule than when using peritumoral HBP hypointensity alone (P<0.001). Conclusion: In patients without peritumoral HBP hypointensity, a radiological capsule is useful for identifying MVI and satellite nodule is an independent risk factor for intrahepatic RFS.

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features.

Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared ALK rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential ALK-tyrosine kinase inhibitor (TKI) targeted therapy, both the patient's primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to ALK-TKIs. Subsequently, the patient's respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of ALK-TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same EML4-ALK rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.

Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells.

Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA.Here, we demonstrate a covalent chemistry-based nanostructured silicon substrate ("Click Chip") for CTC purification that leverages bioorthogonal ligation-mediated CTC capture and disulfide cleavage-driven CTC release. This platform is ideal for CTC mRNA assays because of its efficient, specific, and rapid purification of pooled CTCs, enabling downstream molecular quantification using reverse transcription Droplet Digital polymerase chain reaction. Rearrangements of ALK/ROS1 were quantified using CTC mRNA and matched with those identified in biopsy specimens from 12 patients with late-stage non-small cell lung cancer. Moreover, CTC counts and copy numbers of ALK/ROS1 rearrangements could be used together for evaluating treatment responses and disease progression.

Bio-Inspired NanoVilli Chips for Enhanced Capture of Tumor-Derived Extracellular Vesicles: Toward Non-Invasive Detection of Gene Alterations in Non-Small Cell Lung Cancer.

Tumor-derived extracellular vesicles (EVs) present in bodily fluids are emerging liquid biopsy markers for non-invasive cancer diagnosis and treatment monitoring. Because the majority of EVs in circulation are not of tumor origin, it is critical to develop new platforms capable of enriching tumor-derived EVs from the blood. Herein, we introduce a biostructure-inspired NanoVilli Chip, capable of highly efficient and reproducible immunoaffinity capture of tumor-derived EVs from blood plasma samples. Anti-EpCAM-grafted silicon nanowire arrays were engineered to mimic the distinctive structures of intestinal microvilli, dramatically increasing surface area and enhancing tumor-derived EV capture. RNA in the captured EVs can be recovered for downstream molecular analyses by reverse transcription Droplet Digital PCR. We demonstrate that this assay can be applied to monitor the dynamic changes of ROS1 rearrangements and epidermal growth factor receptor T790M mutations that predict treatment responses and disease progression in non-small cell lung cancer patients.