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Background:The miRNA deregulation is commonly observed in human malignancies, where they act as tumour suppressors or oncogenes. Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs that contribute to bladder cancer progression from non-muscle invasive (NMI) to muscle-invasive (MI) disease.Methods:We first profiled the expression of miRNAs and mRNAs in a cohort of urothelial carcinomas and further characterised the role of miR-126 in invasion, as it emerged as the most downregulated miRNA between MI and NMI tumours.Results:We found that restoration of miR-126 levels attenuated the invasive potential of bladder cancer cells. Mechanistically, we identified the role of miR-126 in invasion through its ability to target ADAM9. Notably, a significant inverse correlation between miR-126 and ADAM9 expression was observed, where ADAM9 was upregulated in MI bladder cancer cells. While knockdown of ADAM9 attenuated the invasiveness of cells with low miR-126 levels, experimental upregulation of ADAM9 recapitulated the invasive phenotype. Furthermore, ADAM9 expression assessed by immunohistochemistry significantly correlated with poor prognosis in patients with urothelial carcinoma.Conclusions:In this study we describe the role of miR-126 in bladder cancer progression, identifying miR-126 and ADAM9 as potential clinical biomarkers of disease aggressiveness.

BACKGROUND: Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. METHODS: A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. RESULTS: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. CONCLUSIONS: This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

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PurposeTo evaluate the role of adjuvant radiotherapy after narrow-margin (<1.0 cm) resection in patients with intrahepatic cholangiocarcinoma (ICC) adherent to major vessels.Patients and methodsThis retrospective study included 70 ICC patients. Forty-nine patients received narrow-margin (<1.0 cm) hepatectomy and 21 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Twenty-six of 49 were treated with postoperative radiotherapy (Group A), while the remaining 23 did not receive radiotherapy (Group B). Clinical outcomes were compared in the 3 groups. Toxicities of radiotherapy were evaluated.ResultsWith a median follow-up time of 42 months, the 3-year overall survival (OS) and disease-free survival rates were 55% and 44% for Group A, 20% and 10% for Group B, and 65% and 33% for Group C, respectively. The OS and disease-free survival in Groups A and C were comparable and improved compared to Group B (Group A vs B, P=0.011 and P=0.031; and Group C vs B, P=0.031 and P=0.105). Multivariate analysis showed that receiving narrow-margin resection only (adjusted hazard ratio: 3.73; 95% CI: 1.36–10.25; P=0.001) was a significant poor prognostic risk factor of OS. Group B experienced more intrahepatic recurrence and extrahepatic recurrence than Groups A and C. For Groups A and B, the 3-year intrahepatic recurrence rates were 36% vs 67% (P=0.133) and extrahepatic recurrence rates were 43% vs 65% (P=0.007). Only 2 patients in Group A suffered from grade 3 toxicities. No patient developed classic or nonclassic radiation-induced liver disease.ConclusionPostoperative radiotherapy following narrow-margin hepatectomy seems to be efficacious and well-tolerated in patients with ICC adjacent to major vessels.

miRNAs are small noncoding RNAs with critical roles in a large variety of biological processes such as development and tumorigenesis. miRNA expression profiling has been reported to be a powerful tool to classify tissue samples, including cancers, based on their developmental lineage. In this study, we have profiled the expression of miRNAs in bladder carcinoma in situ (CIS) and distinct cell compartments of the normal bladder, namely umbrella and basal-intermediate urothelial cells, as well as the muscularis propria. We identified several miRNAs differentially expressed between umbrella and basal-intermediate cells (miR-133a, miR-139-3p, miR-142-3p, miR-199b-5p, and miR-221). In situ hybridization confirmed the expression of miR-133a and miR-139-3p in umbrella cells, and miR-142-3p in basal-intermediate cells. Strikingly, miRNA expression levels of CIS most closely resembled the miRNA profile of umbrella cells. Finally, we examined well-established umbrella and basal-intermediate cell immunohistochemical biomarkers in an independent series of CIS samples. Again, this analysis revealed the significant expression of umbrella-specific markers in CIS when compared to non-CIS lesions. Overall, our studies represent a comprehensive and accurate description of the different miRNAs expressed in CIS tumors and three distinct histological areas of the urinary bladder. Notably, this study provides evidence of the possible origin relationship between CIS and normal umbrella cells.

AimsTo assess motion magnitude in different parts of the liver through surgical clips in postoperative patients with hepatocellular carcinoma and to examine the correlation between the clip and diaphragm motion.MethodsFour-dimensional computed tomography images from 30 liver cancer patients under thermoplastic mask immobilization were selected for this study. Three to seven surgical clips were placed in the resection cavity of each patient. The liver volume on computed tomography image was divided into the right upper (RU), right middle (RM), right lower (RL), hilar, and left lobes. Agreement between the clip and diaphragm motion was assessed by calculating intraclass correlation coefficient, and Bland–Altman analysis (Diff). Furthermore, population-based and patient-specific margins for internal motion were evaluated.ResultsThe clips located in the RU lobe showed the largest motion, (7.5±1.6) mm, which was significantly more than in the RM lobe (5.7±2.8 mm, p=0.019), RL lobe (4.8±3.3 mm, p=0.017), and hilar lobe (4.7±2.7 mm, p<0.001) in the cranial–caudal direction. The mean intraclass correlation coefficient values between the clip and diaphragm motion were 0.915, 0.735, 0.678, 0.670, and the mean Diff values between them were 0.1±0.8 mm, 2.3±1.4 mm, 3.1±2.0 mm, 2.4±1.5 mm, when clips were located in the RU lobe, RM lobe, RL lobe, and hilar lobe, respectively. The clip and diaphragm motions had high concordance when clips were located in the RU lobe. Internal margin can be reduced from 5 mm in the cranial–caudal direction based on patient population average and to 3 mm based on patient-specific margins.ConclusionsThe motion magnitude of clips varied significantly depending on their location within the liver. The diaphragm was a more appropriate surrogate for tumor located in the RU lobe than for other lobes.

Three-dimensional conformal radiotherapy in combination with transarterial chemoembolization (TACE) has been beneficial in patients with unresectable hepatocellular carcinoma (HCC). There have been few clinical reports on the use of intensity-modulated radiotherapy (IMRT) in combination with TACE for these patients. The purpose of this study was to assess the efficacy and toxicity of IMRT following TACE in unresectable HCC.The medical records of consecutive patients with unresectable HCC, who underwent IMRT following TACE from January 2009 to June 2014, were retrospectively reviewed in order to assess the overall survival (OS), progression-free survival (PFS), tumor response, and treatment-associated toxicity.A total of 64 lesions in 54 patients were included in the analysis. IMRT was delivered at a median dose of 50 Gy (range 44–70 Gy) at 1.8 to 2.0 Gy per fraction. The overall response rate was achieved in 64.8% of patients with complete response in 20.4% of patients at 3 months after completion of IMRT. The median OS was 20.2 months (95% CI = 8.6–31.9), and the actuarial 1-, 2-, and 3-year OS rates were 84.6%, 49.7%, and 36.7%, respectively. The median PFS was 10.5 months (95% CI = 7.3–13.7) and the 1-, 2-, and 3-year PFS rates were 44.2%, 23.4%, and 14.6%, respectively. The responders had a significantly higher OS rate than the nonresponders (3-year OS 48.0% vs 14.4%, P = 0.001). During and the first month following IMRT, 10 (18.5%) patients developed grade 3 hematological toxicity, and 3 (5.6%) developed grade 3 hepatic toxicity. No patient experienced grade 4 or 5 toxicity. Radiation-induced liver disease was not observed.Our findings suggest that IMRT following TACE could be a favorable treatment option for both its safety profile and clinical benefit in patients with unresectable HCC.