Combined Hepatocellular-Cholangiocarcinoma With Ductal Plate Malformation Pattern: A Case Report With Molecular Analysis.

Combined hepatocellular-cholangiocarcinoma with a ductal plate malformation pattern is an extremely rare entity with unelucidated pathogenesis. We present the case of a 60-year-old male patient who underwent a sectionectomy for pre-operative diagnosis of hepatocellular carcinoma based on clinical and image findings. Gross examination of the specimen revealed a well-defined tumor with cystic change measuring 6.7 × 6.2 cm. Microscopically, the lesion had classical features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma exhibited neoplastic glands with irregular-sized dilated lumens, resembling a ductal plate malformation. Postoperative diagnosis was combined hepatocellular-cholangiocarcinoma with ductal plate malformation pattern. Next-generation sequencing revealed genomic alteration in 15 genes: CDKN2A, CHD4, CYP2D6, ERBB3, KIR3DL1, KRAS, MDM2, PIM1, STAT6, TPMT amplification, FANCD2, FAT1, FLT4, RASA1, and TP53 point mutation. This is the first case report of molecular alteration in combined hepatocellular-cholangiocarcinoma with ductal plate malformation pattern.

FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients.

BACKGROUND: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. METHODS: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. RESULTS: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. CONCLUSIONS: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer.

In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.

Correlation of PIK3CA mutation with programmed death ligand-1 (PD-L1) expression and their clinicopathological significance in colorectal cancer.

BACKGROUND: The prognostic significance of PIK3CA mutations in colorectal cancer (CRC) remains controversial. Recently, an association between programmed death ligand-1 (PD-L1) and PIK3CA mutations has been reported. The study presented here was conducted to investigate the effect of PIK3CA mutations on the prognosis of CRC patients and the association between PIK3CA mutations and PD-L1. METHODS: PIK3CA mutations were analyzed by targeted next-generation sequencing using formalin-fixed paraffin-embedded specimens from 224 primary CRC patients. PD-L1 expression was evaluated by immunohistochemical staining. RESULTS: PIK3CA mutations and PD-L1 expression were detected in 21.4% and 10.3% of CRC patients, respectively. PIK3CA mutations were significantly correlated with right-side colon cancer (P=0.011) and were correlated inversely with lymph node metastasis (P=0.026), distant metastasis (P=0.047), and high TNM stage (P=0.036). In univariate analysis, PIK3CA mutations were correlated with longer relapse-free survival in CRC patients. PD-L1 expression was correlated significantly with PIK3CA mutations (P<0.001). CONCLUSIONS: PIK3CA mutations were associated with favorable prognostic factors, longer relapse-free survival, and expression of PD-L1. Further investigation is needed to identify whether PIK3CA mutations are a good prognostic factor. Additionally, further studies are needed to understand the mechanisms behind the correlation between PIK3CA mutations and PD-L1 expression.

FAM83H and Nectin1 expression are related with survival and relapse of bladder urothelial carcinoma patients.

BACKGROUND: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. METHODS: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. RESULTS: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. CONCLUSIONS: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.

SCRIB Is Involved in the Progression of Ovarian Carcinomas in Association with the Factors Linked to Epithelial-to-Mesenchymal Transition and Predicts Shorter Survival of Diagnosed Patients.

SCRIB is a polarity protein important in maintaining cell junctions. However, recent reports have raised the possibility that SCRIB might have a role in human cancers. Thus, this study evaluated the roles of SCRIB in ovarian cancers. In 102 human ovarian carcinomas, nuclear expression of SCRIB predicted shorter survival of ovarian carcinoma patients, especially in the patients who received post-operative chemotherapy. In SKOV3 and SNU119 ovarian cancer cells, overexpression of SCRIB stimulated the proliferation and invasion of cells. Knockout of SCRIB inhibited in vivo tumor growth of SKOV3 cells and overexpression of SCRIB promoted tumor growth. Overexpression of SCRIB stimulated epithelial-to-mesenchymal transition by increasing the expression of N-cadherin, snail, TGF-ß1, and smad2/3, and decreasing the expression of E-cadherin; the converse was observed with inhibition of SCRIB. In conclusion, this study presents the nuclear expression of SCRIB as a prognostic marker of ovarian carcinomas and suggests that SCRIB is involved in the progression of ovarian carcinomas by stimulating proliferation and epithelial-to-mesenchymal transition-related invasiveness.

Diagnostic pitfall of thyroid fine-needle aspiration induced fibrosis: follicular adenoma mimicking medullary thyroid carcinoma in frozen section.

BACKGROUND: Fine-needle aspiration (FNA) is a frequently utilized method for the diagnosis of thyroid nodules. Although the technique has clear advantages, the injury caused by the aspiration needle can induce various histological alterations. Herein, we report a case of follicular adenoma showing histological alterations possibly caused by FNA biopsy. Furthermore, the histological appearance of the lesion mimicked those of medullary thyroid carcinoma, particularly in the frozen section. CASE PRESENTATION: Ultrasonography of a thyroid nodule in a 39-year-old man revealed a mass (2.2 cm in diameter) in the right thyroid lobe. FNA was performed three times on the mass, and the results of the cytology were atypia of undetermined significance. Thereafter, the patient underwent right hemithyroidectomy. The histological findings of the operative frozen section analysis indicated medullary thyroid carcinoma. However, after evaluation and immunohistochemical staining of the permanent section, the mass was diagnosed as follicular adenoma with extensive fibrosis. CONCLUSION: The histological alterations observed in the follicular adenoma are believed to have been caused by injury during the repeated FNA procedures.

FAM83H and SCRIB stabilize ß-catenin and stimulate progression of gastric carcinoma.

FAM83H primarily is known for its function in tooth development. Recently, a role for FAM83H in tumorigenesis, conjunction with MYC and ß-catenin, has been suggested. Analysis of public data indicates that FAM83H expression is closely associated with SCRIB expression in human gastric cancers. Therefore, this study investigated the roles of FAM83H and SCRIB in 200 human gastric cancers and gastric cancer cells. In human gastric carcinomas, both the individual and combined expression patterns of the nuclear FAM83H and SCRIB were independent indicators of shorter survival of gastric carcinoma patients. In MKN-45 and NCI-N87 gastric cancer cells, the expression of FAM83H and SCRIB were associated with proliferation and invasiveness of cells. FAM83H-mediated in vivo tumor growth was attenuated with knock-down of SCRIB. Moreover, immunoprecipitation indicates that FAM83H, SCRIB, and ß-catenin, form a complex, and knock-down of either FAM83H or SCRIB accelerated proteasomal degradation of ß-catenin. In conclusion, this study has found that the individual and combined expression patterns of nuclear FAM83H and SCRIB are prognostic indicators of gastric carcinomas and further suggests that FAM83H and SCRIB are involved in the progression of gastric carcinomas by stabilizing ß-catenin.

A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy.

BACKGROUND: Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. METHODS: Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses ('not-NASH,' 'borderline,' and 'NASH') of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. RESULTS: Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52-0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. CONCLUSIONS: A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study.

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

FAM83H is involved in stabilization of ß-catenin and progression of osteosarcomas.

BACKGROUND: FAM83H was initially identified as a protein essential for dental enamel formation. Recent reports have shown that FAM83H is also involved in the progression of human cancers in conjunction with tumor-associated molecules, such as MYC and ß-catenin. However, the role of FAM83H in sarcoma has not yet been investigated. METHODS: The expression and roles of FAM83H and ß-catenin were evaluated in human osteosarcomas from 34 patients and osteosarcoma cells. RESULTS: The expression of nuclear FAM83H, cytoplasmic FAM83H, and ß-catenin were significantly associated with each other and significantly associated with shorter survival of osteosarcoma patients by univariate analysis. In multivariate analysis, cytoplasmic expression of FAM83H was an independent indicator of shorter survival of osteosarcoma patients (overall survival; P <  0.001, relapse-free survival; P <  0.001). In U2OS, MG63, and KHOS/NP osteosarcoma cells, the knock-down of FAM83H decreased proliferation and invasion activity and overexpression of FAM83H increased proliferation and invasion activity. In KHOS/NP cells, knock-down of FAM83H significantly inhibited, and overexpression of FAM83H significantly increased in vivo growth of cells. In addition, the knock-down of FAM83H decreased protein expression of ß-catenin, active ß-catenin, cyclin D1, vimentin, and snail. Overexpression of FAM83H increased protein expression of ß-catenin, active ß-catenin, cyclin D1, vimentin, and snail. However, the expression of ß-catenin mRNA was not significantly altered with knock-down or overexpression of FAM83H. In addition, FAM83H and ß-catenin shown to directly interact via immunoprecipitation and nuclear and cytoplasmic localization of ß-catenin was decreased with knock-down of FAM83H. Moreover, the ubiquitination and proteasomal degradation of ß-catenin was increased with knock-down of FAM83H. CONCLUSIONS: This study suggests that FAM83H is involved in the progression of osteosarcomas via a mechanism involving the stabilization of ß-catenin and the promotion of proliferation and invasiveness of osteosarcomas.

Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer.

BACKGROUND: Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC). METHODS: We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking. RESULTS: The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05). CONCLUSIONS: The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.

The Expression Patterns of FAM83H and PANX2 Are Associated With Shorter Survival of Clear Cell Renal Cell Carcinoma Patients.

FAM83H is primarily known for its role in amelogenesis; however, recent reports suggest FAM83H might be involved in tumorigenesis. Although the studies of FAM83H in kidney cancer are limited, a search of the public database shows a significant association between FAM83H and pannexin-2 (PANX2) in clear cell renal cell carcinomas (CCRCCs). Therefore, we evaluated the clinicopathological significance of the immunohistochemical expression of FAM83H and PANX2 in 199 CCRCC patients. The expression of FAM83H and PANX2 were significantly associated with each other. In univariate analysis, individual, and co-expression pattern of FAM83H and PANX2 was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients: nuclear expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), nuclear expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; P < 0.001, RFS; P < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; P < 0.001, RFS; P = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; P < 0.001, RFS; P < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS (P = 0.030) in multivariate analysis. In Caki-1 and Caki-2 CCRCC cells, knock-down of FAM83H decreased PANX2 expression and cell proliferation, and overexpression of FAM83H increased PANX2 expression and cell proliferation. These results suggest that FAM83H and PANX2 might be involved in the progression of CCRCC in a co-operative manner, and their expression might be used as novel prognostic indicators for CCRCC patients.

SIRT6 Is Involved in the Progression of Ovarian Carcinomas via ß-Catenin-Mediated Epithelial to Mesenchymal Transition.

SIRT6 is involved in various cellular signaling pathways including those involved in tumorigenesis in association with ß-catenin. However, the role of SIRT6 in tumorigenesis has been controversially reported and the studies on the role of SIRT6 in ovarian cancers is limited. In this study, we evaluated the expression and roles of SIRT6 in conjunction with the expression of active ß-catenin in 104 human ovarian carcinomas and ovarian cancer cells. In human ovarian carcinomas, the expressions of SIRT6 and active ß-catenin were associated with higher tumor stage, higher histologic grade, and platinum-resistance. Moreover, nuclear expression of SIRT6 (104 ovarian carcinomas; P = 0.010, 63 high-grade serous carcinomas; P = 0.040), and activated ß-catenin (104 ovarian carcinomas; P = 0.013, 63 high-grade serous carcinomas; P = 0.005) were independent indicators of shorter overall survival of ovarian carcinoma patients in multivariate analysis. In OVCAR3 and OVCAR5 ovarian cancer cells, knock-down of SIRT6 significantly inhibited the migration and invasion of cells, but did not inhibit the proliferation of cells. SIRT6-mediated invasiveness of ovarian cancer cells was associated with the expression of epithelial-to-mesenchymal transition-related signaling molecules such as snail, vimentin, N-cadherin, E-cadherin, and activated ß-catenin. Especially, SIRT6-mediated increase of invasiveness and activation of epithelial-to-mesenchymal transition signaling was attenuated by knock-down of ß-catenin. In conclusion, this study suggests that SIRT6-ß-catenin signaling is involved in the epithelial-to-mesenchymal transition of ovarian cancer cells, and the expression of SIRT6 and active ß-catenin might be used as indicators of poor prognosis of ovarian carcinoma patients. In addition, our results suggest that SIRT6-ß-catenin signaling might be a new therapeutic target of ovarian carcinomas.

Combined expression of protein disulfide isomerase and endoplasmic reticulum oxidoreductin 1-α is a poor prognostic marker for non-small cell lung cancer.

Protein disulfide isomerase (PDI) is one of the most abundant proteins in the endoplasmic reticulum (ER) and is known as a primary ER resident target of cigarette smoke-induced oxidation. PDI dysfunction triggers unfolded protein response and ER stress. Endoplasmic reticulum oxidoreductin 1-α (ERO1A) is a major regulator of PDI, and recent evidence implicates PDI and ERO1A as tumor prognostic factors. However, the associated role of PDI and ERO1A and their prognostic impact in non-small cell lung cancers (NSCLCs) remains unknown. The present study investigated the expression of PDI and ERO1A using immunohistochemistry and examined its association with smoking status and their prognostic impact in 198 NSCLCs. PDI and ERO1A expression were observed in 71.2 and 69.2% of NSCLCs, respectively, and their expressions were significantly associated with each other (P<0.001). Individual PDI (P=0.001) and ERO1A (P=0.005) expression were significantly associated with shorter overall survival (OS) in univariate analysis. PDI expression was significantly associated with never smoking (P=0.003). PDI expression (P<0.001) and the co-expression of PDI and ERO1A (P<0.001) were independent poor prognostic factors for OS in patients with NSCLC in multivariate analysis. Individual expression and co-expression of PDI and ERO1A may be used as novel prognostic indicators of NSCLC outcome.

Expression of oxidized protein tyrosine phosphatase and γH2AX predicts poor survival of gastric carcinoma patients.

BACKGROUND: Oxidative stress induces various intracellular damage, which might be correlated with tumorigenesis. Accumulated oxidative stresses might inactivate protein tyrosine phosphatase (PTP) by oxidizing it, and inducing the phosphorylation of H2AX (γH2AX) in response to DNA damage. METHODS: We evaluated the clinical significance of the expression of oxidized-PTP and γH2AX in 169 gastric carcinomas. RESULTS: Immunohistochemical expression of nuclear oxidized-PTP, cytoplasmic oxidized-PTP, and γH2AX expression were significantly associated with each other, and their expressions predicted shorter survival of gastric carcinoma patients. In multivariate analysis, nuclear oxidized-PTP (overall survival; p <  0.001, relapse-free survival; P <  0.001) was an independent indicator of poor prognosis of gastric carcinoma patients. In addition, co-expression patterns of nuclear oxidized-PTP and γH2AX were independent indicators of poor prognosis of gastric carcinoma patients (overall survival; P <  0.001, relapse-free survival; P <  0.001). CONCLUSIONS: This study suggests that oxidative stress-mediated oxidation of PTP might be involved in the progression of gastric carcinomas. In addition, this study suggests that individual and co-expression pattern of nuclear oxidized-PTP and γH2AX might be used as a prognostic marker of gastric carcinomas.

The PARP inhibitor olaparib potentiates the effect of the DNA damaging agent doxorubicin in osteosarcoma.

BACKGROUND: PARP1 facilitates the recovery of DNA-damaged cells by recruiting DNA damage response molecules such as γH2AX and BRCA1/2, and plays a role in resistance to antitumor therapies. Therefore, PARP inhibition being evaluated as an anti-cancer therapy. However, there are limited studies regrading PARP inhibition in osteosarcoma. METHODS: We evaluated the expression of DNA damage response molecules in 35 human osteosarcomas and investigated the effects of co-treatment of the PARP inhibitor, olaparib, and doxorubicin in osteosarcoma cells. RESULTS: The expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 were significantly associated with shorter survival of osteosarcoma patients. In osteosarcoma cells, knock-down of PARP1 and treatment of olaparib significantly inhibited proliferation of cells and induced apoptosis. Moreover, the anti-tumor effect was more significant with co-treatment of olaparib and doxorubicin in vitro and in vivo. CONCLUSIONS: This study suggests that combined use of a PARP inhibitor with doxorubicin, a DNA damaging agent, might be effective in the treatment of osteosarcoma patients, especially in the poor-prognostic subgroups of osteosarcoma expressing PARP1, γH2AX, or BRCA1/2.

Hypovascular hypointense nodules in hepatobiliary phase without T2 hyperintensity: long-term outcomes and added value of DWI in predicting hypervascular transformation.

PURPOSE: To evaluate outcomes and risk factors associated with hypervascularization in hypovascular, hepatobiliary phase (HBP) hypointense nodules (HHNs) without T2 hyperintensity on gadoxetic acid-enhanced magnetic resonance (MR) images in chronic liver disease patients. MATERIALS AND METHODS: 222 HHNs were analyzed. Multivariate analysis with a Cox proportional hazard regression model was used. RESULTS: 41 nodules became hypervascular hepatocellular carcinoma (HCC). History of HCC, hyperintensity on T1WI or DWI, and higher growth rate were risk factors for hypervascularization (P < .05). CONCLUSION: History of HCC, hyperintensity on T1WI or DWI, and higher growth rate were associated with nodular progression to hypervascular HCC.

Intra-individual comparison of hepatocellular carcinoma imaging features on contrast-enhanced computed tomography, gadopentetate dimeglumine-enhanced MRI, and gadoxetic acid-enhanced MRI.

Background Gadoxetic acid is being widely used for detection and characterization of hepatic nodules. However, there are no data regarding intra-individual comparison of imaging features of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT), gadopentetate dimeglumine-enhanced magnetic resonance imaging (Gd-DTPA-MRI), and gadoxetic acid-enhanced MRI (Gd-EOB-MRI). Purpose To evaluate typical imaging features of HCC and capsule appearance with dynamic CT, Gd-DTPA-MRI, and Gd-EOB-MRI. Material and Methods We retrospectively reviewed 56 HCCs in 49 patients. Lesion attenuation/signal intensity was graded using a five-point scale based on dynamic phase and hepatobiliary phase (HBP) imaging. Subjective washout and capsule appearance were evaluated on portal venous phase (PVP) or delayed/transitional phase (DP/TP) imaging. The tumor-to-liver contrast ratio (TLCR) was calculated. Results Gd-DTPA-MRI and Gd-EOB-MRI was graded higher than CT on arterial phase ( P < 0.001). Gd-EOB-MRI was graded lower than Gd-DTPA-MRI on PVP and DP/TP ( P < 0.05). The detection rate of subjective washout and capsule appearance did not differ among the three imaging studies on either PVP or DP/TP. TLCR of Gd-EOB-MRI was lower than CT on PVP ( P = 0.004) and was lower than Gd-DTPA-MRI on DP/TP ( P = 0.001). Conclusion Arterial phase hyperenhancement and washout appearance of HCC were well demonstrated in Gd-EOB-MRI. The detection of capsule appearance using Gd-EOB-MRI was not inferior to Gd-DTPA-MRI or CT.