Blood Perfusion Characteristics of Renal Cell Carcinoma in the Process of Tumor Growth: Monitored With Multiple Sonographic Modalities.

ABSTRACT: Tumor angiogenesis is an essential factor for tumor growth and antiangiogenic therapy. To simulate the blood perfusion characteristics of human renal cell carcinoma (RCC) longitudinally in the process of tumor growth, multimodal ultrasound examination was performed on 40 orthotopic xenograft RCC mouse models. According to tumor maximum diameter ( d ), tumor growth progress was divided into 3 steps: d ≤ 5 mm, 5 mm < d ≤ 10 mm, and d > 10 mm. Color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound were administered to monitor tumor perfusion characteristics. The abundance of tumor vascularity on CDFI and SMI was divided into grades 0 to III in ascending order, and their distribution range was categorized into types I to IV. As a result, heterogeneous echogenicity and irregular shape were more common in tumors d > 10 mm than those d < 10 mm ( P < 0.001 for both). Tumor perfusion grade and type on both CDFI and SMI made statistic difference among different growth steps, with higher ratio of hypervascular characteristic in bigger ones (all P < 0.05). Tumor in the same growth step had a higher perfusion grade on SMI than that on CDFI ( P < 0.001). On contrast-enhanced ultrasound, heterogeneous enhancement was more common in those >10 mm ( P < 0.001). It can be concluded that the blood perfusion characteristics of RCC keep on changing during its growth process. In addition, SMI is more sensitive in evaluating tumor perfusion than CDFI.

Quantitative evaluation of contrast-enhanced ultrasound for differentiation of renal cell carcinoma subtypes and angiomyolipoma.

PURPOSE: To investigate the value of quantitative parameters of contrast-enhanced ultrasound (CEUS) in the differentiation of subtypes of renal cell carcinoma (RCC) and angiomyolipoma (AML). METHODS: The quantitative characteristics of 341 RCCs and 88 AMLs were analyzed with quantitative software (SonoLiver). Quantitative analysis was conducted in the whole tumor (ROItumor) and the maximum enhanced area of the tumor (ROImax), acquiring the parameters of maximum intensity (IMAX), rise time (RT), time to peak (TTP), mean transit time (mTT), and area under the curve (AUC), were derived and analyzed. The difference values between ROImax and normal renal cortex (ΔPar.s, including ΔIMAX, ΔRT, ΔTTP, ΔmTT, ΔAUC) were compared among renal histotypes. RESULTS: All time-related parameters (including RT, TTP and mTT) of ROImax were shorter than the corresponding parameters of ROItumor in RCC subtypes (all p<0.05), but made no statistical difference in AMLs (all p>0.05). There were significant differences of all ΔPar.s among RCC subtypes and AML (all p<0.01). ΔIMAX and ΔAUC showed the trend that ccRCC>AML>pRCC=chRCC. ΔTTP showed AML=pRCC=chRCC>ccRCC, ΔRT and ΔmTT showed AML>pRCC=chRCC=ccRCC. ΔmTT could distinguish RCC from AML with the area under the ROC curve (AUC) of 0.86. The AUC of ΔIMAX and ΔAUC was 0.89 and 0.92 vs 0.85 and 0.85 for discriminating between pRCC (or chRCC) and AML vs ccRCC and AML. CONCLUSIONS: Quantitative analysis of CEUS is a useful modality in AML and RCC subtypes' differentiation, by using ΔmTT, ΔIMAX and ΔAUC.

Deficiency of sorting nexin 10 prevents bone erosion in collagen-induced mouse arthritis through promoting NFATc1 degradation.

OBJECTIVE: Periarticular and subchondral bone erosion in rheumatoid arthritis caused by osteoclast differentiation and activation is a critical index for diagnosis, therapy and monitoring of the disease. Sorting nexin (SNX) 10, a member of the SNX family which functions in regulation of endosomal sorting, has been implicated to play an important clinical role in malignant osteopetrosis. Here we studied the roles and precise mechanisms of SNX10 in the bone destruction of collagen-induced arthritis (CIA) mice. METHODS: The role of SNX10 in bone destruction was evaluated by a CIA mice model which was induced in male SNX10(-/-) mice and wild type littermates. The mechanism was explored in osteoclasts induced by receptor activator of nuclear factor κB ligand from bone marrow mononuclear cells of wild type and SNX10(-/-) mice. RESULTS: SNX10 knockout prevented bone loss and joint destruction in CIA mice with reduced serum levels of TNF-α, interleukin 1ß and anticollagen IgG 2α antibody. SNX10 deficiency did not block osteoclastogenesis, but significantly impaired osteoclast maturation and bone-resorption function by disturbing the formation of actin belt. The production of TRAP, CtsK and MMP9 in SNX10(-/-) osteoclasts was significantly inhibited, and partially restored by SNX10 overexpression. We further demonstrated that the degradation of NFATc1 was accelerated in SNX10(-/-) osteoclasts causing an inhibition of integrin ß3-Src-PYK2 signalling. CONCLUSIONS: Our study discloses a crucial role and novel mechanism for SNX10 in osteoclast function, and provides evidence for SNX10 as a promising novel therapeutic target for suppression of immune inflammation and bone erosion in rheumatoid arthritis.

Differentiation of subtypes of renal cell carcinoma with contrast-enhanced ultrasonography.

We aimed to assess the difference of enhancement patterns among the three RCC subtypes with contrast-enhanced ultrasound (CEUS). Two hundreds cases of pathologically proved clear cell renal cell carcinomas (ccRCC), 58 papillary renal cell carcinomas (pRCC) and 51 chromophobe renal cell carcinomas (chRCC) underwent preoperative conventional ultrasound and CEUS. The wash-in and wash-out pattern, peak enhancement degree and homogeneity, and the presence of pseudocapsule were evaluated by two blinded observers respectively. The interreader agreement in the characterization of CEUS features between two observers was good (κ  = 0.649-0.775). Compared with pRCCs and chRCCs, ccRCCs demonstrated higher frequency of simultaneous wash-in pattern, hyperenhancement and heterogeneity with necrotic areas. Most pRCCs and chRCCs manifested hypoenhancement, homogeneity, fast wash-out and presence of pseudocapsule. The only difference we obtained between pRCC and chRCC was the wash-in pattern, with slow wash-in in pRCC and simultaneous wash-in in chRCC. In small lesions with long diameter≤3 cm, the majority of the three subtypes of RCC showed homogeneous enhancement and there was no difference among them. CEUS was a useful method to preoperatively differentiate the ccRCC from non-ccRCC subtypes. There were no distinguishing features identifid on CEUS that allowed reliable differentiation of pRCC from chRCC.

Comparison of retraction phenomenon and BI-RADS-US descriptors in differentiating benign and malignant breast masses using an automated breast volume scanner.

OBJECTIVE: To compare the diagnostic values of retraction phenomenon in the coronal planes and descriptors in the Breast Imaging Reporting and Data System-Ultrasound (BI-RADS-US) lexicon in differentiating benign and malignant breast masses using an automated breast volume scanner (ABVS). MATERIALS AND METHODS: Two hundred and eight female patients with 237 pathologically proven breast masses (120 benign and 117 malignant) were included in this study. ABVS was performed for each mass after preoperative localization by conventional ultrasonography (US). Multivariate logistic regression analysis was performed to assess independent variables for malignancy prediction. Diagnostic performance was evaluated through the receiver operating characteristic (ROC) curve analysis. RESULTS: Retraction phenomenon (odds ratio [OR]: 76.70; 95% confidence interval [CI]: 12.55, 468.70; P<0.001) was the strongest independent predictor for malignant masses, followed by microlobulated margins (OR: 55.87; 95% CI: 12.56, 248.44; P<0.001), angular margins (OR: 36.44; 95% CI: 4.55, 292.06; P=0.001), calcifications (OR: 5.53; 95% CI: 1.34, 22.88; P=0.018,) and patient age (OR: 1.10; 95% CI: 1.03, 1.17; P=0.004). Mass shape, orientation, echo pattern, indistinct margins, spiculated margins, and mass size were not significantly associated with breast malignancy. Area under the ROC curve (Az) for microlobulated margins and retraction phenomenon was higher than that for other significant independent predictors. Az, sensitivity, and specificity were 0.877 (95% CI: 0.829, 0.926) and 0.838 (95% CI: 0.783, 0.892), 82.9% and 70.1%, and 92.5% and 98.3%, respectively, for microlobulated margins and retraction phenomenon. CONCLUSIONS: Retraction phenomenon and microlobulated margins have high diagnostic values in the differentiation of benign and malignant breast masses using an ABVS.

Papillary renal cell carcinoma and clear cell renal cell carcinoma: Differentiation of distinct histological types with contrast - enhanced ultrasonography.

PURPOSE: Papillary renal cell carcinoma (pRCC) and clear cell renal cell carcinoma (ccRCC) have different biological behaviours and imaging features. The role of contrast-enhanced ultrasound (CEUS) in differentiating these two carcinoma subtypes has not been comprehensively studied. MATERIALS AND METHODS: Forty-eight patients with 49 pRCC lesions and 153 patients with 156 ccRCC lesions underwent preoperative conventional ultrasound (US) and CEUS. Among them, 91 patients (25 pRCCs and 66 ccRCCs) also underwent preoperative contrast-enhanced computed tomography (CECT) in our hospital. The characteristics of CEUS and CECT images for each patient imaged were analysed by each of two blinded observers. RESULTS: Images for five (5/25, 20%) pRCC patients demonstrated equivocal or no enhancement using CECT, while all lesions were enhanced using CEUS. From CEUS, images of pRCCs, when compared with ccRCC images, demonstrated significantly higher frequencies of slow wash-in (59.2% vs. 5.8%), fast wash-out (87.7% vs. 46.1%), and hypo-enhancement (57.1% vs. 7.1%) patterns, p<0.001, as well as the presence of pseudocapsule (42.9% vs. 23.1%), p=0.007. For lesions with large diameters (> 3 cm), a higher percentage of pRCC images demonstrated homogeneous enhancement compared with ccRCC images. Using the combination of slow wash-in, fast wash-out, and hypoenhancement patterns at peak as criteria to differentiate pRCC from ccRCC, positive and negative predictive value, and sensitivity and specificity were found to be 86.7%, 86.9%, 53.1%, and 97.4%, respectively. CONCLUSIONS: CEUS imaging features of slow-in, fast-out, and hypo-enhancement patterns may be useful for differentiating pRCC and ccRCC. In addition, CEUS may be helpful for diagnosing hypovascular renal lesions that demonstrate equivocal or no enhancement by CECT and, thus, for improving diagnostic confidence.

Qualitative and quantitative analysis with contrast-enhanced ultrasonography: diagnosis value in hypoechoic renal angiomyolipoma.

OBJECTIVE: To evaluate the value of enhancement features and quantitative parameters of contrast-enhanced ultrasonography (CEUS) in differentiating solid hypoechoic renal angiomyolipomas (AMLs) from clear cell renal cell carcinomas (ccRCCs). MATERIALS AND METHODS: We analyzed the enhancement features and quantitative parameters of CEUS in 174 hypoechoic renal masses (32 AMLs and 142 ccRCCs) included in the study. RESULTS: Centripetal enhancement pattern was more common in AMLs than in ccRCCs on CEUS (71.9% vs. 23.2%, p < 0.001). At peak enhancement, all AMLs showed homogeneous enhancement (100% in AML, 27.5% in ccRCCs; p < 0.001). Quantitative analysis showed no significant difference between rise time and time to peak. Tumor-to-cortex (TOC) enhancement ratio in AMLs was significantly lower than that in ccRCCs (p < 0.001). The criteria of centripetal enhancement and homogeneous peak enhancement together with TOC ratio < 91.0% used to differentiate hypoechoic AMLs from ccRCCs resulted in a sensitivity and specificity of 68.9% and 95.8%, respectively. CONCLUSION: Both qualitative and quantitative analysis with CEUS are valuable in the differential diagnosis of hypoechoic renal AMLs from ccRCCs.

Dynamic enhancement pattern of intrahepatic cholangiocarcinoma on contrast-enhanced ultrasound: the correlation with cirrhosis and tumor size.

PURPOSE: To retrospectively evaluate the dynamic enhancement pattern of contrast-enhanced ultrasound (CEUS) in intrahepatic cholangiocarcinoma (ICC) of varying sizes and hepatic backgrounds. MATERIALS AND METHODS: CEUS was performed in 98 pathologically confirmed ICCs (n = 39 < 30 mm, n = 59 > 30 mm; n = 45 with cirrhosis and n = 53 with normal liver). The dynamic enhancement pattern of CEUS was retrospectively analyzed. RESULTS: In the arterial phase, heterogeneous hyper-enhancement was more frequent in ICCs with cirrhosis (21/45, 46.7% vs. 11/53, 20.8% in ICCs with normal liver, p = 0.009), while peripheral hyper-enhancement and hypo-enhancement were more common in ICCs with normal liver (14/53, 26.4%; 11/53, 20.8% vs. 2/45, 4.4%; 2/45, 4.4% in ICCs with cirrhosis, p = 0.005 and 0.033, respectively). There were no significant differences between portal and delayed phases. In ICCs < 30 mm, homogeneous hyper-enhancement was more frequently identified (27/39, 69.2% vs. 10/59, 16.9% in ICCs > 30 mm, p < 0.001), whereas in ICCs > 30 mm, heterogeneous, and peripheral hyper-enhancement were more commonly observed (26/59, 44.1% vs. 6/39, 15.4% in ICCs < 30 mm, p = 0.004, and 14/59, 23.7% vs. 2/39, 5.1% in ICCs < 30 mm, p = 0.023, respectively). The washout pattern in portal and delayed phases were not significantly different in ICCs with different sizes. 60.7% (17/28) ICCs < 30 mm and 85.2% (23/27) ICCs > 30 mm with cirrhosis, together with 66.7% (14/21) ICCs < 30 mm with normal liver displayed intense contrast agent uptake (homogeneous or heterogeneous hyper-enhancement) in arterial phase followed by washout in portal and delayed phase, which was much higher than that in ICCs > 30 mm with normal liver (34.4%, 11/32, p < 0.001, <0.001 and =0.027, respectively). CONCLUSION: The CEUS dynamic enhancement pattern of ICC varies with size and hepatic background. The enhancement pattern is indistinguishable from hepatocellular carcinoma on CEUS in most ICCs with cirrhosis and in most ICCs < 30 mm with normal liver.

Histotype differentiation of hypo-echoic renal tumors on CEUS: usefulness of enhancement homogeneity and intensity.

PURPOSE: The purpose of this study is to evaluate qualitative and quantitative analysis of contrast-enhanced ultrasound (CEUS) in differential diagnoses of hypo-echoic renal tumor histotypes. METHODS: Our study cohort comprised 103 clear cell renal cell carcinomas (ccRCCs), 24 papillary renal cell carcinomas (pRCCs), 28 chromophobe renal cell carcinomas (cRCCs), and 34 angiomyolipomas (AMLs), hypo-echoic on ultrasound, and imaged between January 2011 and December 2013. Enhancement homogeneity and tumor-to-cortex intensity ratio (TOC ratio) were retrospectively analyzed. RESULTS: Overall, heterogeneous enhancement was more common in ccRCCs than AMLs, pRCCs, and cRCCs. TOC ratio showed the trend ccRCC > AML > pRCC = cRCC. Similar trends were seen in tumors <4 cm. Using heterogeneous enhancement or TOC ratio >107.5% to differentiate ccRCC from other histotypes, the sensitivity, specificity, positive and negative predictive values were 93.1%, 74.5%, 84.8%, and 87.5%, respectively. Tumors >4 cm exhibited considerable overlap in enhancement homogeneity among different histotypes. TOC ratios were similar between homo- and heterogeneously enhancing tumors for ccRCCs and for pRCCs and cRCCs, but higher in homogeneously enhancing than heterogeneously enhancing AMLs. In homo- and heterogeneously enhancing tumors, TOC ratios followed the trends ccRCCs > AMLs > pRCCs = cRCCs and ccRCCs > AMLs = pRCCs = cRCCs, respectively. With TOC ratio >105.81% and >72.37% to differentiate homo- and heterogeneously enhancing ccRCCs from other histotypes in tumors >4 cm with same enhancement homogeneity, the sensitivity, specificity, positive and negative predictive values were 70.0%, 85.7%, 70.0%, 85.7%, and 91.7%, 94.4%, 95.7%, 89.5%, respectively. CONCLUSION: CEUS homogeneity and TOC ratio are helpful in differential diagnosis of hypo-echoic renal tumor histotypes. Diameter and enhancement homogeneity should be considered when deciding the diagnostic TOC ratio cutoff.

Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

PURPOSE: To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. METHODS: Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. RESULTS: No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p < 0.001 for both), homogeneous peak enhancement (100.0% in both EAMLs and TAMLs vs. 43.4% in ccRCCs, p < 0.001 for both), and iso-enhancement in parenchyma phase (53.3% in AMLs, 52.0% in TAMLs vs. 26.5% in ccRCCs, p = 0.034 and 0.013, respectively) were valuable traits for differentiating EAMLs and TAMLs from ccRCCs. Furthermore, with quantitative analysis, RT and TTP were much shorter in ccRCCs than those in EAMLs and TAMLs. However, all these qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p < 0.001), and TOC ratio was much higher in EAMLs (166.01 ± 64.47%) than that in TAMLs (93.74 ± 46.56%)(p < 0.001), though they did make overlaps with ccRCCs. With either heterogeneous peak enhancement or the presence of pseudocapsule or TOC ratio >97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. CONCLUSIONS: Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

The value of contrast-enhanced ultrasound (CEUS) in detecting minute renal cell carcinoma.

UNLABELLED: To investigate the value of contrast-enhanced ultrasound (CEUS) in the detection of minute renal cell carcinoma (MRCC) compared to conventional ultrasound (US) and contrast-enhanced computed tomography (CECT). METHODS: Thirty-eight consecutive patients with 38 histopathologically proven MRCCs (≦15 mm) were enrolled in our study. CEUS and CECT were available in 38 and 24 patients, respectively. The features of CEUS were evaluated and compared to conventional ultrasound (US) and CECT. RESULTS: Ten (26.3%) tumors could not be detected by conventional US, while all tumors were detected by CEUS. The features of tumor border, blood flow, and echogenicity had significant difference between conventional US and CEUS (p=0.000, p=0.003, and p=0.012, respectively). The score of visibility of tumors by CEUS was significant higher than that of conventional US. The sensitivity, specificity, and accuracy of conventional US and CEUS in evaluating tumor necrosis were 42.9%, 50%, and 47.4% vs. 85.7%, 95.8%, and 92.1%, respectively. The enhancement features of MRCC including tumor vascularization, homogeneity, and border had no significant difference between CEUS and CECT (all p>0.05). On CEUS, synchronous-in (89.5%), hypervascular (84.2%), and fast-out (71.1%) were the most commonly observed enhancement characteristics for MRCC. CONCLUSION: CEUS performs better in detecting MRCC than conventional US, and it has the same capabilities in reflecting the enhanced features of MRCC as CECT.

[Effects of electroacupuncture on glutamate and aspartic acid contents in the dorsal root ganglion and spinal cord in rats with neuropathic pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain threshold and contents of excitatory amino acids (EAA) in dorsal root ganglia (DRG) and spinal cord in rats with neuropathic pain. METHODS: Fifty SD rats were randomly divided into control (C),model (M), sham-model (SM), EA, and sham-EA groups, with 10 cases in each. Neuropathic pain (spared nerve injury, SNI) model was established by cutting off the right common peroneal nerve and proso-tibial nerve (with the sural nerve reserved intact). Before and after surgery, the mechanical pain threshold (MPT) and thermal pain threshold (TPT) were measured respectively on the injured side under consciousness state. EA (2 Hz, 1-3 mA, adding 1 mA/10 min) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) on the affected side for 30 min. For rats of sham-EA group, filiform needles were inserted into GB30 and BL40 simply without manipulation or electrical stimulation. The treatment was given once daily for 7 days. On the 15th day, the rats were sacrificed for sampling right L4-L6 DRG and spinal cord. The contents of neurotransmitters, glutamate (Glu) and aspartic acid (Asp) in DRG and spinal cord were detected with high performance liquid chromatography (HPLC). Micro-dialysis technique was used to collect the dialysate from the spinal cord, homogenated for measuring EAA by HPLC. RESULTS: In comparison with control group, after SNI, MPT decreased significantly from the 1st day on in model group. Compared with model group, on the 15th day, MPT increased significantly in both EA and sham-EA groups (P < 0.05, 0.01),but MPT of sham-EA was significantly lower than that of EA group (P < 0.05). No significant changes were found in TPT in 5 groups (P > 0.05). It suggested that sham EA still had an analgesic effect in spite of being lower than that of true EA. Compared with control group, the contents of Glu and Asp in the spinal cord tissue and micro-dialysate in model group increased significantly after SNI (P < 0.01). In comparison with model group, the contents of Glu in DRG and spinal cord tissue and micro-dialysate, and Asp in the spinal cord tissue and micro-dialysate in both sham-EA and EA groups decreased considerably (P < 0.05, 0.01). Dialysate Glu and spinal cord tissue Asp contents in EA were remarkably lower than those in sham-EA group (P < 0.01, 0.05). CONCLUSION: EA has a significant analgesic effect in SNI rats, which is closely related with its effect in inhibiting the release of Glu and Asp from dorsal horns of the spinal cord and lowering contents of EAAs.