Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6–8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
CXCR5 mediates homing of both B and follicular helper T (TFH) cells into follicles of secondary lymphoid organs. We found that CXCR5+CD8+ T cells are present in human tonsils and follicular lymphoma, inhibit TFH-mediated B-cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5+CD8+ T cells into an animal model of lymphoma resulted in significantly greater antitumor activity than CXCR5−CD8+ T cells. Furthermore, RNA-Seq-based transcriptional profiling revealed a 77-gene signature unique to CXCR5+CD8+ T cells. The upregulated 33 genes among the 77-gene signature correlated with improved survival in follicular lymphoma patients. We also showed that CXCR5+CD8+ T cells could be induced and expanded ex vivo using IL-23 plus TGF-β, suggesting a possible strategy to generate these cells for clinical application. In summary, our study identified CXCR5+CD8+ T cells as a distinct T-cell subset with ability to suppress TFH-mediated B-cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.
Background: Pneumothorax is the most common complication of computed tomography (CT)-guided needle biopsy. The purpose of this study was to investigate independent risk factors of pneumothorax, other than emphysema, after CT-guided needle biopsy and to establish a risk prediction model. Methods: A total of 864 cases of CT-guided needle biopsy with an 18-gauge cutting needle were enrolled in this study. The relevant risk factors associated with pneumothorax included age, sex, emphysema, shortaxis size of the lesion, depth of the lesion, body position, and the number of pleural punctures. Several independent risk factors of pneumothorax were found, and a predictive model for pneumothorax was established using univariate and multivariate logistic regression analyses. Results: Pneumothorax occurred in 31.4% (271/864) of cases. Univariate analysis showed that significant risk factors of pneumothorax included age, emphysema, small lesion size, no contact between the lesion and the pleura, prone or lateral body position, and multiple punctures. Independent risk factors of pneumothorax in the multivariate logistic regression analysis included emphysema (P=0.000), no contact between the lesion and the pleura (P=0.000), prone or lateral body position (P=0.002), and the number of pleural punctures (P=0.000). The sensitivity, specificity, and accuracy of the predictive model for pneumothorax were 56.8%, 79.6%, and 72.5%, respectively. Conclusions: Pneumothorax is a common complication of CT-guided lung biopsy. Independent risk factors of pneumothorax include emphysema, no contact between the lesion and the pleura, and prone or lateral body position. The predictive model developed in this study was highly accurate in predicting the incidence of pneumothorax.
PurposeTo prospectively investigate the effect of using Gemstone Spectral Imaging (GSI) and adaptive statistical iterative reconstruction (ASIR) for reducing radiation and iodine contrast dose in abdominal CT patients with high BMI values.Materials and Methods26 patients (weight > 65kg and BMI ≥ 22) underwent abdominal CT using GSI mode with 300mgI/kg contrast material as study group (group A). Another 21 patients (weight ≤ 65kg and BMI ≥ 22) were scanned with a conventional 120 kVp tube voltage for noise index (NI) of 11 with 450mgI/kg contrast material as control group (group B). GSI images were reconstructed at 60keV with 50%ASIR and the conventional 120kVp images were reconstructed with FBP reconstruction. The CT values, standard deviation (SD), signal-noise-ratio (SNR), contrast-noise-ratio (CNR) of 26 landmarks were quantitatively measured and image quality qualitatively assessed using statistical analysis.ResultsAs for the quantitative analysis, the difference of CNR between groups A and B was all significant except for the mesenteric vein. The SNR in group A was higher than B except the mesenteric artery and splenic artery. As for the qualitative analysis, all images had diagnostic quality and the agreement for image quality assessment between the reviewers was substantial (kappa = 0.684). CT dose index (CTDI) values for non-enhanced, arterial phase and portal phase in group A were decreased by 49.04%, 40.51% and 40.54% compared with group B (P = 0.000), respectively. The total dose and the injection rate for the contrast material were reduced by 14.40% and 14.95% in A compared with B.ConclusionThe use of GSI and ASIR provides similar enhancement in vessels and image quality with reduced radiation dose and contrast dose, compared with the use of conventional scan protocol.
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