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BackgroundThe optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI.MethodsIn this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1–2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events.ResultsBetween June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3–48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99–29.14) vs. 9.27 months (95% CI 6.05–13.70), hazard ratio [HR] = 0.70 (95% CI 0.52–0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99–62.58) vs. 22.37 months (95% CI 10.84–33.91), HR = 0.68 (95% CI 0.48–0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.ConclusionHepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.

Copy number alteration (CNA) is a major contributor to genome instability, a hallmark of cancer. Here, we studied genomic alterations in single primary tumor cells and circulating tumor cells (CTCs) from the same patient. Single-nucleotide variants (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumor cells emerged accumulatively rather than abruptly, converging toward the CNA in CTCs. Focal CNAs affecting the gene and the gene were observed only in a minor portion of primary tumor cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variant (SV) analyses revealed a two-step mechanism, a complex rearrangement followed by gene amplification, for the simultaneous formation of anomalous CNAs in multiple chromosome regions. Integrative CNA analyses of 97 CTCs from 23 patients confirmed the convergence of CNAs and revealed single, concurrent, and mutually exclusive CNAs that could be the driving events in cancer metastasis.

BackgroundProstate-specific membrane antigen (PSMA) has been found in tumor neovasculature endothelial cells (NECs) of non-prostate cancers and may become the most promising target for anti-tumor therapy. To study the value of PSMA as a potential new target for lung cancer treatment, PSMA expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) tissues and its relationship with clinicopathology were investigated in the current study.MethodsImmunohistochemistry was used to detect PSMA expression in a total of 150 lung specimens of patients with lung cancer. The data were analyzed using univariate and multivariate statistical analyses.ResultsThe percentages of NSCLC patients who had PSMA (+) tumor cells and PSMA (+) NECs were 54.02% and 85.06%, respectively. The percentage of patients younger than 60 years old who had PSMA (+) tumor cells was 69.05%, which was significantly greater than the percentage of patients aged 60 years or older (40.00%, p<0.05). A significant difference was observed in the percentage of NSCLC patients with PMSA (+) NECs and stage I or II cancer (92.98%) and those patients with stage III or IV cancer (76.77%). In the SCLC tissues, NEC PSMA expression (70.00%) did not differ significantly from NSCLC. SCLC tumor cells and normal lung tissues cells were all negative. There was no significant correlation between the presence of PSMA (+) NECs in SCLC patients and the observed clinicopathological parameters.ConclusionsPSMA is expressed not only in NECs of NSCLC and SCLC but also in tumor cells of most NSCLC patients. The presence of PSMA (+) tumor cells and PSMA (+) NECs in NSCLC was negatively correlated with age and the clinicopathological stage of the patients, respectively.

IntroductionRadiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial–mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects.Materials and methodsIn this study, we prepared an apatinib microcrystal formulation (Apa-MS) that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors.ResultsIt was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial–mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment.ConclusionBased on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC.

• US-CNB is useful for the diagnosis of cervical lymphadenopathy. • US-CNB is safe to perform on lymph nodes located near vital structures. • Larger, malignant, level IV lymph nodes yield sufficient tissue samples more easily.

Background: Autophagy is a self-digesting process that can satisfy the metabolic needs of cells, and is closely related to development of cancer. However, the effect of autophagy-related genes (ARGs) on the prognosis of breast cancer remains unclear. Results: We first found that 27 ARGs were significantly associated with overall survival in breast cancer. The prognosis-related ARGs signature established using the Cox regression model consists of 12 ARGs that can be divided patients into high-risk and low-risk groups. The overall survival of patients with high-risk scores (HR 3.652, 2.410-5.533; P < 0.001) was shorter than patients with low-risk scores. The area under the receiver operating characteristic (ROC) curve for 1-year, 3-year, and 5-year survival rates were 0.739, 0.727, and 0.742, respectively. Conclusion: The12-ARGs marker can predict the prognosis of breast cancer and thus help individualized treatment of patients at different risks. Methods: Based on the TCGA dataset, we integrated the expression profiles of ARGs in 1,039 breast cancer patients. Differentially expressed ARGs and survival-related ARGs were evaluated by computational difference algorithm and COX regression analysis. In addition, we also explored the mutations in these ARGs. A new prognostic indicator based on ARGs was developed using multivariate COX analysis.

Medullary thyroid carcinoma (MTC) is highly malignant and quite different from the most common papillary thyroid carcinoma (PTC). However, most of the ultrasonic evaluation systems mainly aim at PTC at present. This study aims to evaluate the applicability of modified TI‐RADS in diagnosing MTC and compare the sonographic differences of MTC, PTC, and benign nodules. Three thousand two hundred and forty‐two thyroid nodules images confirmed by pathology were categorized according to modified TI‐RADS and ACR TI‐RADS classification. The performances of two TI‐RADS were assessed by ROC curves. The correlations between classifications with the pathology and the consistency of different doctors were evaluated. The ultrasonic differences of MTC, PTC, and benign nodules were analyzed. As a result, the number of high suspicious US features increased, the malignant risk of nodules also increased of two classifications, with significant differences between categories ( P < 0.001). Spearman correlation coefficients were 0.751 (modified TI‐TADS) and 0.744 (ACR TI‐RADS). Areas under the ROC curve of the modified TI‐RADS and ACR TI‐RADS were 0.960 and 0.872 ( P < 0.001). At Best cut off points, the diagnostic value of modified TI‐RADS was higher than that of ACR TI‐RADS with a higher specificity, PPV, accuracy, and Youden index). By using modified TI‐RADS to diagnose MTC and PTC, the sensitivity, specificity, NPV, accuracy, and Youden index were higher in MTC than PTC. The Kendall's correlation coefficients were 0.962, 0.930, and 0.987. MTC had special ultrasonography characters compared with PTC and benign nodules. These results suggest that modified TI‐RADS is better than ACR TI‐RADS in diagnosing thyroid carcinomas. Diagnostic value to MTC of modified TI‐RADS is slightly higher than that to PTC, and the categorical results of different doctors were consistent. MTC had several particular features contrast to PTC and benign nodules.