The role of cuproptosis-related gene in the classification and prognosis of melanoma.

Background: Melanoma, as one of the most aggressive and malignant cancers, ranks first in the lethality rate of skin cancers. Cuproptosis has been shown to paly a role in tumorigenesis, However, the role of cuproptosis in melanoma metastasis are not clear. Studying the correlation beteen the molecular subtypes of cuproptosis-related genes (CRGs) and metastasis of melanoma may provide some guidance for the prognosis of melanoma. Methods: We collected 1085 melanoma samples in The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus(GEO) databases, constructed CRGs molecular subtypes and gene subtypes according to clinical characteristics, and investigated the role of CRGs in melanoma metastasis. We randomly divide the samples into train set and validation set according to the ratio of 1:1. A prognostic model was constructed using data from the train set and then validated on the validation set. We performed tumor microenvironment analysis and drug sensitivity analyses for high and low risk groups based on the outcome of the prognostic model risk score. Finally, we established a metastatic model of melanoma. Results: According to the expression levels of 12 cuproptosis-related genes, we obtained three subtypes of A1, B1, and C1. Among them, C1 subtype had the best survival outcome. Based on the differentially expressed genes shared by A1, B1, and C1 genotypes, we obtained the results of three gene subtypes of A2, B2, and C2. Among them, the B2 group had the best survival outcome. Then, we constructed a prognostic model consisting of 6 key variable genes, which could more accurately predict the 1-, 3-, and 5-year overall survival rates of melanoma patients. Besides, 98 drugs were screened out. Finally, we explored the role of cuproptosis-related genes in melanoma metastasis and established a metastasis model using seven key genes. Conclusions: In conclusion, CRGs play a role in the metastasis and prognosis of melanoma, and also provide new insights into the underlying pathogenesis of melanoma.

Potential diagnostic performance of contrast-enhanced ultrasound and tumor markers in differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and cholangiocarcinoma.

PURPOSE: To evaluate the diagnostic performance of the combination of tumor markers [alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9)] and imaging features in differentiating combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). METHODS: Forty consecutive patients with pathologically proven CHC were retrospectively evaluated with contrast-enhanced ultrasound (CEUS). Additionally, 40 HCC and 40 CC patients who were randomly selected from the same period served as a control group. Images were classified as HCC-like or CC-like pattern according to CEUS guidelines recommended by World and European Federation for Ultrasound in Medicine and Biology (WFUMB-EFSUMB). The diagnostic criteria of CHC were defined as follows: (1) both AFP and CA19-9 are simultaneously elevated (AFP > 20 ng/ml and CA19-9 > 100 units/ml); or (2) elevated AFP with a CC-like pattern on CEUS and without elevated CA19-9 level; or (3) elevated CA19-9 with an HCC-like pattern on CEUS and without elevated AFP level. The diagnostic tests were performed with calculation of the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). RESULTS: For the 40 CHC patients, the rates of elevated AFP and CA19-9 serology were 55.0 and 30.0%, respectively. Twenty-three (57.5%) patients exhibited an HCC-like pattern, and 15 (37.5%) showed a CC-like pattern. After applying the above diagnostic criteria of CHC in the 120 patients, the sensitivity, specificity, PPV, NPV, accuracy, and AUC were 32.5, 93.8, 72.2, 73.5, 73.3, and 0.631%, respectively. When the actual prevalence rate (0.4-14.3%) was taken into account, the PPV and NPV were modified from 2.1 to 46.7% and 89.3 to 99.7%, respectively. CONCLUSION: The combination of enhancement patterns on CEUS and serum tumor markers (AFP and CA19-9) may be a potentially specific diagnostic method to differentiate CHC from HCC and CC.

Transabdominal Ultrasound Colonography for Detection of Colorectal Neoplasms: Initial Clinical Experience.

We investigated the feasibility of using ultrasound colonography (USC) to visualize the healthy colon and rectum and detect colorectal polyps. Eight healthy volunteers underwent USC after standard bowel preparation. The feasibility and image quality of USC in different segments were evaluated. Then, USC was conducted on eight patients with known colonic neoplasms using colonoscopy as the reference standard. For volunteers, USC examinations were successfully performed on four (50.0%) ascending, three (37.5%) transverse and eight (100%) descending colons, as well as all sigmoid colons and rectums. One of four (25.0%) ascending, two of eight (25.0%) descending and all sigmoid colons and rectums were well visualized and free of artifacts. For patients, colonoscopy revealed that eight patients had 17 neoplasms in the distal sigmoid colon and rectum, which included 3 lesions ≤5 mm, 3 lesions 6-9 mm and 11 lesions ≥10 mm. USC visualized 12 of 17 (70.6%) neoplasms. Lesion detection by USC was 0% (0/3), 33.3% (1/3) and 100% (11/11) for neoplasms ≤5, 6-9 mm and ≥10 mm in size. USC can visualize the sigmoid colon and rectum well and detect distal sigmoid and rectal neoplasms ≥10 mm in diameter.

Assessment of Rectal Tumors with Shear-Wave Elastography before Surgery: Comparison with Endorectal US.

Purpose To compare the value of endorectal ultrasonography (US) with shear-wave elastography (SWE) in staging rectal tumors before surgery. Materials and Methods This prospective study was approved by the institutional review board and written informed consent was obtained. In a pilot cohort from April 2015 to January 2016, 70 patients with rectal adenocarcinomas and/or adenomas confirmed with histopathologic examination underwent both endorectal US and SWE. Tumor stiffness and three regions of reference backgrounds, as well as tumor stiffness ratios (SRs) versus these backgrounds, were analyzed. The optimal staging feature was selected by using receiver operating characteristic analysis, and the concordance rate with pathologic stage was analyzed and compared with endorectal US. The results were validated in an independent cohort of 30 patients from February 2016 to July 2016. Results In the pilot study, from rectal adenoma to stage T3 cancers, the tumor stiffness, stiffness of peritumoral fat, tumor SR versus distant perirectal fat, and tumor SR versus normal rectal wall were significantly increased (all P < .05, correlation coefficients between SWE features and pathologic T stages were 0.589-0.853). Receiver operating characteristic analysis of tumor staging demonstrated that tumor stiffness was the optimal feature with the highest area under the receiver operating characteristic curve (AUC = 0.991-1.000). The cutoff values of stage T1, T2, and T3 cancers were 26.9 kPa, 70.3 kPa, and 112.0 kPa, respectively. For SWE, the diagnostic concordance rate with pathologic stage (95.7%, weighted κ = 0.962) was higher than that of endorectal US (75.7%, weighted κ = 0.756). In the validation cohort, similar findings were revealed for diagnostic concordance rate (93.3% vs 76.7%; weighted κ = 0.927 vs 0.651) and diagnostic performance of tumor staging (AUC = 0.950-1.000 vs 0.700-0.833). Conclusion By using the feature of tumor stiffness at SWE, the accuracy of preoperative staging for rectal tumors was improved compared with endorectal US in the pilot study, but was not significantly different in the validation cohort, potentially due to small sample size. © RSNA, 2017 Online supplemental material is available for this article.

Diagnostic nomogram for gallbladder wall thickening mimicking malignancy: using contrast-enhanced ultrasonography or multi-detector computed tomography?

OBJECTIVES: To establish a diagnostic nomogram using contrast-enhanced ultrasonography (CEUS) in gallbladder wall thickening mimicking malignancy and compare with multi-detector computed tomography (MDCT). METHODS: Seventy-two patients with gallbladder wall thickening on B-mode ultrasonography (BUS) were examined by CEUS to develop independent predictors for diagnosing gallbladder carcinoma. Among the 72 cases, 48 patients underwent both CEUS and MDCT. The diagnostic performances of different sets of CEUS criteria and MDCT were compared. A prediction model of malignancy using CEUS was developed. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. RESULTS: Multivariate logistic regression indicated that inhomogeneous enhancement in the arterial phase was the strongest independent predictor of malignancy (odds ratio, OR 51.162), followed by interrupted inner layer (OR 19.788), washout time ≤40 s (OR 16.686), and wall thickness >1.6 cm (OR 3.019), which were all selected into the nomogram. Combined with the above significant features, the diagnostic performance of CEUS (AUC = 0.917) was higher than that of MDCT (AUC = 0.788, P = 0.070). The predictive model using CEUS showed good discrimination, with a concordance index of 0.974 (0.950 through internal validation), and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: CEUS could accurately differentiate between malignant and benign gallbladder wall thickening with equivalent efficacy compared to MDCT. The proposed nomogram could be conveniently used to facilitate the preoperative individualized prediction of malignancy in patients with gallbladder wall thickening.

Hilar biliary neurofibroma without neurofibromatosis: case report with contrast-enhanced ultrasound findings.

Solitary neurofibroma located in the hilum of the liver is extremely rare, particularly without neurofibromatosis. We herein report a case of hilar biliary neurofibroma without signs of von Recklinghausen's disease. A 36-year-old man was admitted to our department with progressive jaundice. The case was diagnosed as hilar cholangiocarcinoma based on preoperative imaging. The patient consequently received a Roux-en-Y hepaticojejunostomy and was confirmed with neurofibroma pathologically. This is the first reported imaging finding of hilar biliary neurofibroma using contrast-enhanced ultrasound, emphasizing the differential diagnosis of biliary tumors.

Hepatocellular adenoma: comparison between real-time contrast-enhanced ultrasound and dynamic computed tomography.

PURPOSE: To investigate and compare the contrast-enhanced ultrasound (CEUS) features of histologically proven HCA with those of contrast-enhanced computed tomography (CECT). METHODS: Eighteen patients with proven hepatic adenoma by pathology were retrospectively selected from the CEUS database. Fourteen of them had undergone liver CECT exams. The basic features on unenhanced imaging and the enhancement level and specific features on contrast-enhanced imaging were retrospectively analyzed, and the differences between CEUS and CECT were compared. RESULTS: All the HCAs showed hyper-enhancement in the arterial phase. During the portal and late phases, 12 HCAs (12/18, 66.7 %) on CEUS and 11 (11/14, 78.6 %) on CT showed washout. On CEUS, 10 (10/18, 55.5 %) showed centripetal filling in the arterial phase and persistent peripheral rim enhancement. Five of them (61.1 %, 11/18) showed delayed central washout in the portal or late phase. However, on CECT, 2 (14.3 %, 2/14) and 4 (28.6 %, 4/14) HCAs showed persistent enhancement of the peripheral rim and central non-enhancing hemorrhage areas, respectively. CONCLUSIONS: Compared with dynamic CT, CEUS was superior at characterizing specific dynamic features. Considering that it is radiation-free, readily availability and easy to use, CEUS is suggested as the first line imaging tool to diagnose HCA.

Ultrasound virtual endoscopy: Polyp detection and reliability of measurement in an in vitro study with pig intestine specimens.

AIM: To present our initial experience regarding the feasibility of ultrasound virtual endoscopy (USVE) and its measurement reliability for polyp detection in an in vitro study using pig intestine specimens. METHODS: Six porcine intestine specimens containing 30 synthetic polyps underwent USVE, computed tomography colonography (CTC) and optical colonoscopy (OC) for polyp detection. The polyp measurement defined as the maximum polyp diameter on two-dimensional (2D) multiplanar reformatted (MPR) planes was obtained by USVE, and the absolute measurement error was analyzed using the direct measurement as the reference standard. RESULTS: USVE detected 29 (96.7%) of 30 polyps, remaining a 7-mm one missed. There was one false-positive finding. Twenty-six (89.7%) of 29 reconstructed images were clearly depicted, while 29 (96.7%) of 30 polyps were displayed on CTC with one false-negative finding. In OC, all the polyps were detected. The intraclass correlation coefficient was 0.876 (95%CI: 0.745-0.940) for measurements obtained with USVE. The pooled absolute measurement errors ± the standard deviations of the depicted polyps with actual sizes ≤ 5 mm, 6-9 mm, and ≥ 10 mm were 1.9 ± 0.8 mm, 0.9 ± 1.2 mm, and 1.0 ± 1.4 mm, respectively. CONCLUSION: USVE is reliable for polyp detection and measurement in in vitro study.

Focal Lesions in Fatty Liver: If Quantitative Analysis Facilitates the Differentiation of Atypical Benign from Malignant Lesions.

To evaluate the diagnostic performance of quantitative analysis as an adjunctive diagnostic tool to contrast-enhanced ultrasound (US) for the differentiation of atypical benign focal liver lesions (FLLs) from malignancies in fatty liver. Twenty-seven benign FLLs and fifty-six malignant FLLs that appeared hyper-enhanced during the arterial phase with washout in the portal or late phase in fatty liver were analyzed. Chi-square tests and logistic regression were applied to identify the specific features. Three sets of criteria were assigned: 1) all FLLs subjected to routine contrast-enhanced US; 2) all FLLs subjected to quantification analysis and contrast-enhanced US; and 3) parts of FLLs that could not be diagnosed using contrast-enhanced US (n = 66, 75.9%) but instead were diagnosed using parametric features. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) of the three sets of criteria were analyzed. The AUCs of the criterion set 2 were significantly higher than those of criterion set 1 (0.904 versus 0.792, P = 0.008). Criterion set 3 showed a relatively high sensitivity (90.2%) with a relatively high AUC (0.845). The quantification analysis offers improved diagnostic performance for the differential identification of atypical benign FLLs from malignancies in fatty liver.

Assessment of liver fibrosis in chronic hepatitis B using acoustic structure quantification: quantitative morphological ultrasound.

OBJECTIVES: To prospectively investigate the usefulness of acoustic structure quantification (ASQ) for noninvasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with CHB scheduled for liver biopsy or partial liver resection underwent standardized ASQ examinations. The ASQ parameter, named focal disturbance (FD) ratio, were compared with METAVIR scores. The analysis was based on receiver operating characteristic (ROC) curves and multiple regression analysis. RESULTS: A total of 114 patients were enrolled in the final analysis. The area under the ROC curve for the FD ratio was 0.84 for significant fibrosis (≥ F2), 0.86 for severe fibrosis (≥ F3), and 0.83 for cirrhosis (= F4). The optimal cutoff values for the FD ratio were 0.25, 0.30 and 0.50 for fibrosis stages ≥ F2, ≥ F3 and = F4, respectively. The prevalence of a difference of at least two stages between the FD ratio and the histological stage was 12.3 % (14 of 114). The fibrosis stage (P < 0.001), degree of steatosis (P < 0.001) were independent factors associated with the FD ratio. CONCLUSIONS: FD ratio should be an effective noninvasive imaging biomarker for the assessment of liver fibrosis in patients with CHB. KEY POINTS: • Focal disturbance (FD) ratio increased with the increasing histological fibrosis stages. • FD ratio showed promising diagnostic accuracy in assessing liver fibrosis. • Degree of fibrosis and steatosis were independent factors associated with FD ratio.

Contrast-enhanced ultrasound findings in a case of primary chest chondrosarcoma mimicking a porta hepatis mass.

We report a case of a 32-year-old woman who presented with upper abdominal pain. The physical examination revealed a palpable hard mass with a well-demarcated lower margin. Laboratory tests indicated hepatitis B viral infection. Computed tomography scan with intravenous contrast depicted a huge well-demarcated heterogeneous mass at the porta hepatis with irregular peripheral rim enhancement. Contrast-enhanced ultrasound showed peripheral irregular hyper-enhancement in the artery phase and hypo-enhancement in the portal and late phases. The postoperative histopathologic examination confirmed the diagnosis of low-grade chondrosarcoma. This is the first report of contrast-enhanced ultrasound findings of chondrosarcoma. There is some differential diagnosis to be discussed.

Diagnosis of Testicular Adrenal Rest Tumors on Ultrasound: A Retrospective Study of 15 Cases Report.

The aim of this study was to evaluate the imaging features of testicular adrenal rest tumors (TARTs) on baseline ultrasound (BUS).The imaging features of 30 TART lesions pathologically or clinically confirmed in 15 patients who had undergone BUS were evaluated, and the sonographic characteristics of the lesions were analyzed.All 15 cases were bilateral and located near the testicular mediastinum. Approximately 56.7% (17/30) of the TART lesions exhibited homogeneous hypoechogenicity, 36.7% (11/30) of the lesions exhibited heterogeneous hypoechogenicity, and 6.6% (2/30) of the lesions exhibited heterogeneous isoechogenicity. In addition, 76.7% (23/30) of the lesions exhibited a rich blood supply, whereas 23.3% (7/30) of the lesions exhibited a scarce blood supply.The sonographic characteristics of the TARTs were bilateral growth, location adjacent to the testicular mediastinum, hypoechogenicity, and rich blood supply, which may play important roles in early clinical diagnosis.

Differentiation of Atypical Hepatocellular Carcinoma from Focal Nodular Hyperplasia: Diagnostic Performance of Contrast-enhanced US and Microflow Imaging.

PURPOSE: To evaluate diagnostic performance of contrast-enhanced (CE) ultrasonography (US) and microflow (MF) imaging in differentiation of atypical hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH). MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. A total of 103 patients (mean age, 43.9 years; age range, 17-75 years) were included; 38 patients with HCC and 65 with FNH underwent CE US, and vascular architecture pattern (VAP) and arrival time parametric (ATP) images were analyzed. Resident and staff radiologists independently and retrospectively reviewed CE US, VAP, and ATP images. χ(2) test and logistic regression analysis were applied to identify specific features of FNH or HCC on CE US and MF images. To compare diagnostic performance of CE US with or without MF imaging, four sets of criteria were assigned: (a) routine CE US alone, (b) VAP and CE US, (c) ATP imaging and CE US, and (d) all three methods in combination. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of resident and staff radiologists were analyzed. Cohen κ statistic was used to assess agreement of CE US and MF imaging features between staff and resident radiologists. RESULTS: MF imaging offered significant improvements over most detection rates achieved with routine CE US signs in both groups. For staff radiologists, AUCs from criteria sets 3 (AUC = 0.873, P < .05) and 4 (AUC = 0.887, P < .05) were significantly higher than AUC from criteria set 1 (AUC = 0.835). For resident radiologists, specificity (71% and 69% vs 25%, P < .01) and accuracy (78% and 79% vs 50%, P < .01) of criteria sets 3 and 4 were significantly higher than those of criteria set 1. Moreover, AUCs for criteria sets 2 (AUC = 0.728, P < .05), 3 (AUC = 0.823, P < .01), and 4 (AUC = 0.857, P < .01) were significantly higher than those for criteria set 1 (AUC = 0.667). CONCLUSION: When compared with routine CE US, MF imaging can more effectively depict specific features and offers improved diagnostic performance in the differentiation of atypical HCC from FNH, especially when used by resident radiologists. Online supplemental material is available for this article.

Contrast-Enhanced Ultrasound for the Characterization of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

PURPOSE AND METHODS: The ability of contrast-enhanced ultrasound (CEUS) to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is still controversial. We reviewed the CEUS imaging of 819 patients (HCC=546, ICC=273) with an established pathological diagnosis. The enhancement patterns of lesions and the diagnostic performance of CEUS were analyzed. RESULTS: Arterial hyperenhancement followed by washout was observed in 92.3% (504/546) of the HCC lesions and 85.7% (234/273) of the ICC lesions on CEUS (p<0.05). Additionally, the ICCs presented contrast washout much earlier than the HCCs, with an average time of 27.5 seconds after injecting the contrast agent compared with 70.1 seconds for the HCCs (p<0.05). Peripheral rim-like enhancement was observed in 68.5% (187/273) of the ICCs, which was significantly more common than that in the HCCs (2.0%, 11/546) (p<0.05). When using arterial hyperenhancement with a washout phase later than 43 seconds after injecting the contrast agent and with no peripheral rim-like enhancement as the diagnostic criteria for HCC ≤5 cm in diameter, the area under the curve was 0.808, with 64.1% sensitivity, 97.4% specificity and 73.6% accuracy. CONCLUSIONS: Although ICC may show the typical enhancement pattern of HCC on CEUS, peripheral rim-like enhancement and quick contrast washout show high efficiency in the differentiation of HCC from ICC.