[Correlation between the expression profile of cytokeratin 19/glypican 3 and recurrence of hepatocellular carcinoma after interventional therapy].

Objective: To observe the correlation between the expressions profile of cytokeratin 19/glypican 3 (CK19/GPC3) and recurrence of hepatocellular carcinoma after interventional therapy. Methods: Clinical and pathological information of 251 eligible cases with hepatocellular carcinoma who underwent interventional therapy in You'an Hospital from November 2007 to May 2016 were retrospectively collected. Univariate and multivariate Cox regression analysis was used to analyze the relevant risk factors that may affect their prognosis. Kaplan-Meier survival analysis was used to draw the survival curve. Log-rank test was used to compare the difference in survival rates between the groups. Results: Kaplan-Meier univariate analysis showed that histological grade, CK19/GPC3 expression profile, alpha-fetoprotein level and Hep Parl were closely related to tumor recurrence. Multivariate Cox regression analysis showed CK19/GPC3 expression profile (HR = 1.634, 95%CI: 1.041 ~ 2.564, P = 0.033), histological grade (HR = 1.445, 95%CI: 1.037 ~ 2.014, P = 0.030), alpha-fetoprotein level (HR = 1.410, 95%CI: 1.042 ~ 1.908, P = 0.026), Hep Parl (HR = 0.570, 95%CI: 0.349 ~ 0.930, P = 0.025) were the four independent factors for prediction of recurrence after interventional therapy. Conclusion: Hepatocellular carcinoma patients with CK19(+)/GPC3(+) and CK19(-)/GPC3(+) phenotypes who meet the Milan criteria have a higher risk of recurrence after interventional therapy than CK19(-)/GPC3(-) phenotypes.

The value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer.

OBJECTIVE: To explore the clinical application value of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging combined with detection of serum tumor molecular markers (carbohydrate antigen 125 (CA 125) and human epididymis protein 4 (HE4)) in the diagnosis of recurrence and metastasis of ovarian cancer. PATIENTS AND METHODS: Clinical data about 18F-FDG PET/CT imaging and serum CA125 and HE4 of 69 ovarian cancer patients after the first cytoreductive surgery and chemotherapy were retrospectively analyzed, and the clinical application value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer was evaluated. RESULTS: The 18F-FDG PET/CT images of recurrence and metastasis of ovarian cancer showed hypermetabolism. The sensitivity, specificity, accuracy, predictive positive value, and predictive negative value of 18F-FDG PET/CT imaging for the diagnosis of recurrence and metastasis of ovarian cancer were 90.74%, 86.67%, 89.86%, 96.08%, and 72.22%, respectively; those of CA125 for the diagnosis of them were 77.78%, 86.67%, 79.71%, 95.45% and 52.00%, respectively, and those of HE4 for the diagnosis of them were 70.37%, 93.33%, 76.84%, 97.44%, and 48.39% respectively. In addition, the sensitivity and specificity of 18F-FDG PET/CT combined with detection of serum CA125 and HE4 for the diagnosis were 100.00% and 100.00%, respectively, significantly higher than those of separate 18F-FDG PET/CT imaging, detection of serum CA125, and detection of serum HE4 (c2 = 5.243, 13.500, 18.783, p = 0.022, 0.000, 0.000; c2 = 4.000, 8.525, 9.864, p = 0.046, 0.004, 0.002), and the accuracy of the combination use of them was 95.65%, also significantly higher than that of separate CA125 and HE4 (c2 = 8.118, 10.315, p = 0.004, 0.001, both p < 0.01). Furthermore, the maximum standardized uptake value (SUVmax) of 18F-FDG PET/CT imaging for recurrence and metastasis of ovarian cancer focuses was significantly positively correlated with serum CA125 and HE4 levels (r = 0.596, p = 0.000; r = 0.431, p = 0.002), and the serum CA125 level was also significantly positively correlated with serum HE4 level in patients with recurrent or metastasized ovarian cancer (r = 0.198, p = 0.043,). CONCLUSIONS: 18F-FDG PET/CT imaging combined with detection of serum CA125 and HE4 can significantly improve the diagnostic efficiency to recurrence and metastasis of ovarian cancer and is conducive to the early diagnosis of the recurrence and metastasis, which provides a basis for further clinical intervention.

Clinical value of imaging for lymph nodes evaluation with particular emphasis on ultrasonography.

Enlarged or irregular lymph nodes (LNs) are clinical and imaging findings in a large variety of malignant and non-malignant diseases. A comprehensive diagnostic work up is usually necessary in order to differentiate the benign or the malignant nature of the altered LNs. The diagnosis has to be made using all clinical information and, if necessary, assessed LNs need to be biopsied and further, histologically or microbiologically characterized. However, imaging techniques, and particularly ultrasonography (US), are essential on the way to the final diagnosis, from initial detection and characterization to follow-up of biopsy guidance. Computed-tomography (CT) and/or magnetic resonance imaging (MRI) are of great value for oncological diseases staging and treatment monitoring. Imaging techniques are helpful in distinguishing between benign and malignant LNs disease as well as between LNs metastases and lymphoma in most cases. Furthermore, imaging can define the extent and distribution of malignant diseases. It may assist, through the use of particular techniques such as elastography, to identify the most suspicious LN to be biopsied and to guide targeted biopsies from the most suspicious areas. It also serves as the main tool for the evaluation of treatment response in malignant diseases. The quality of LNs imaging has remarkably improved in recent years. New methods, such as contrast-enhanced ultrasonography (CEUS), elastography, positron emission tomography (PET)/PET-CT, as well as diffusion weighted imaging (DWI) in MRI, have already led to substantial changes in clinical practice. This review describes the most recent imaging techniques for LNs assessment, and their particular clinical value, with a special emphasis on the role of US techniques. Strengths and weaknesses of different imaging tools are discussed comprehensively, highlighting the importance of a corroborative attitude for successful management of each particular case.

Evaluation of Strain Elastography for Differentiation of Thyroid Nodules: Results of a Prospective DEGUM Multicenter Study.

PURPOSE: Many patients with thyroid nodules are presently referred to surgery for not only therapeutic but also diagnostic purposes. The aim of noninvasive diagnostic methods is to optimize the selection of patients for surgery. Strain elastography (SE) enables the ultrasound-based determination of tissue elasticity. The aim of the present study was to evaluate the value of SE for the differentiation of thyroid nodules in a prospective multicenter study. MATERIALS AND METHODS: The study was registered at clinicaltrials.gov and was approved by the local ethics committees of all participating centers. All patients received an ultrasound (US) of the thyroid gland including color Doppler US. In addition, all nodules were evaluated by SE (Hitachi Medical Systems) using qualitative image interpretation of color distribution (SE-ES), strain value and strain ratio. RESULTS: Overall, 602 patients with 657 thyroid nodules (567 benign, 90 malignant) from 7 centers were included in the final analysis. The sensitivity, specificity, NPV, PPV, +LR were 21 %, 73 %, 86 %, 11 %, 0.8, respectively, for color Doppler US; 69 %, 75 %, 94 %, 30 %, 2.9, respectively, for SE-ES; 56 %, 81 %, 92 %, 32 %, 2.9, respectively, for SE-strain value; and 58 %, 78 %, 92 %, 30 %, 2.6, respectively, for SE-strain ratio. The diagnostic accuracy was 71 % for both strain value and strain ratio of nodules. CONCLUSION: SE as an additional ultrasound tool improves the value of ultrasound for the work-up of thyroid nodules. It might reduce diagnostic surgery of thyroid nodules in the future.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Short Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Long Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound (INVUS) assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, and safe and effective performance of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (long version).

Local ablative procedures of the liver.

Local ablative therapies have become an important part in the portfolio of treatment for patients with malignant tumors especially in the liver. Although percutaneous ethanol injection still plays a role, current guidelines favor radiofrequency ablation with a higher efficacy for complete tumor destruction. Nevertheless transplantation and surgical resection remain the gold standard due to their superiority in local control and improved survival. In this manuscript we discuss the technique in detail.

Measurement of shear wave velocity using acoustic radiation force impulse imaging is not hampered by previous use of ultrasound contrast agents.

PURPOSE: To assess the inter-observer reproducibility of acoustic radiation force impulse imaging (ARFI) between 2 skilled physicians and to evaluate if ultrasound contrast agents (UCA) affect the measurement of shear wave velocity (SWV) using ARFI. PATIENTS AND METHODS: 53 patients (29 males, 24 females, 59 ± 15 [22-84] years) who underwent contrast enhanced ultrasound (CEUS) examination were included. ARFI was performed on liver segment V by physicians A and B before CEUS, and by physician A within 4-6 minutes and 7-10 minutes after contrast injection. In a subgroup of 31 patients (15 males, 16 females, 57 ± 18 [22-84] years), ARFI was also performed on focal liver lesions (FLL) by physician A before CEUS, and within 4-6 minutes and 7-10 minutes after contrast injection. RESULTS: The SWV values obtained by physician A and B before CEUS yielded an intra-class correlation coefficient value of 0.913 (95% CI, 0.849-0.950). No significant differences were shown between the SWV values of liver segment V in all 53 patients and of FLL in the subgroup of 31 patients obtained before CEUS and that of within 4-6 minutes and 7-10 minutes after contrast injection (all P > 0.05). CONCLUSION: ARFI showed excellent inter-observer reproducibility between 2 skilled physicians. UCA did not affect the measurement of SWV in both liver parenchyma and FLL, at least when performed 4 minutes after the contrast injection. ARFI may become an additional tool in the differential diagnosis of FLL.

CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression.

INTRODUCTION: Pathogenesis of early-onset preeclampsia (PE) is generally recognized by impaired trophoblast invasion of the myometrial arteries, which results in placental insufficiency. Recently, we reported that CDX1 is hypermethylated in the human preeclampsia placenta. However, whether CDX1 participates in trophoblast invasion has not been clearly elucidated. METHODS: We investigated the function of CDX1 in the extravillous trophoblast cell line HTR-8/SVneo using stable transfection of CDX1. Using a CDX1 stable transfected cell line, we determined the cell invasion using a QCM ECMatrix 24-well kit. The cell viability was detected using an MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Quantitative RT-PCR and western blotting analyses were performed to examine the changes in the expression of downstream target genes and proteins. To disrupt PI3K/AKT signaling, we used the PI3K inhibitor perifosine. RESULTS: Cell invasion assays demonstrated that CDX1 restricts trophoblast cell invasiveness. In contrast, quantification of cumulative cell numbers revealed that CDX1 did not affect cell proliferation. Western blotting analysis and quantitative real time PCR demonstrated that MMP-9 expression was reduced, whereas TIMP-1 expression was increased in CDX1-overexpressed cells. However, overexpression of CDX1 did not affect PI3K/AKT signaling in HTR-8/SVneo trophoblast cells. In contrast, CDX1 was regulated by the PI3K/AKT signaling pathway. CONCLUSIONS: Altogether, we found that in trophoblast cells, CDX1 reduced invasion independently of the PI3K/AKT signaling pathway. Furthermore, CDX1 functions in concert with PI3K/AKT signaling to regulate trophoblast invasion. We concluded that CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression independently of the PI3K/AKT pathway.

Conventional ultrasound for lymph node evaluation, update 2013.

Conventional ultrasound is regarded as the first method of choice to evaluate lymph node disease due to its high resolution. The combination of various features obtained from the patients history including age, acute or chronic onset, symptoms, and a knowledge of underlying systemic diseases as well as imaging criteria, most importantly B-mode (gray-scale) and colour Doppler imaging (CDI) are the basis for the differential diagnosis of lymphadenopathy. New ultrasound techniques such as elastography and contrast-enhanced ultrasound may provide further information. In addition, ultrasound evaluation of lymph nodes is an essential adjunct to the clinical investigation in staging of malignant neoplasia and lymphoma. In this paper the current literature is reviewed regarding conventional B-mode and Doppler ultrasound for the evaluation of lymphadenopathy. The ultrasound criteria for the differential diagnosis of enlarged and structurally altered lymph nodes are summarized and also limitations are described.

Prolonged heterogeneous liver enhancement on contrast-enhanced ultrasound.

INTRODUCTION: Prolonged heterogeneous liver enhancement (PHLE) is a rare phenomenon that is similar to the ultrasound findings of portal venous gas. The purpose of this report is to describe the phenomenon of PHLE after the injection of the ultrasound contrast agent SonoVue(®). PATIENTS AND METHODS: From 2000 to 2013, 13 patients with PHLE ("cloudy", "wool-like") after bolus injection of SonoVue(®) were observed. The height, weight, and body mass index (BMI) of the patients, and the number of injections were analyzed. In addition, the literature was reviewed. RESULTS: The phenomenon occurred as early as 2 minutes after bolus contrast administration and lasted up to 5 hours on both B-mode and contrast-specific ultrasound. 8/13 (62 %) patients received two or more boluses. None of the patients experienced SonoVue(®)-related side effects or health problems. The phenomenon was not reproducible in 3 patients who received a second SonoVue(®) injection 24 hours after receiving the first. CONCLUSION: This phenomenon is more likely to occur in patients who receive high-dose (or multiple) injections of UCA. It may occur as early as 2 minutes after contrast administration, and therefore, may affect the evaluation of focal liver lesions in the late phase. This phenomenon should not be misdiagnosed as a pathological finding of the liver.

Dynamic Vascular Pattern (DVP), a quantification tool for contrast enhanced ultrasound.

Contrast-enhanced ultrasound (CEUS) is widely applied in tumour diagnosis, especially for focal liver lesions (FLL), due to its high sensitivity and specificity. According to the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) CEUS guidelines (2012) and non-liver guidelines (2011), the majority of tumours, regardless of location, show specific CEUS enhancement patterns that can distinguish benign from malignant lesions. However, even experienced clinicians evaluating FLL may find occasional irregularities in these patterns, due to particular FLL pathologies, that make a definitive diagnosis difficult. Hence, there is a need to train physicians to utilize contrast enhancement kinetics to aid in the correct interpretation of data from CEUS examinations in patients with divergent liver tumour pathologies. Here we report on a CEUS quantitation software, SonoLiver®, to verify and improve diagnostic accuracy in the characterization of suspicious liver lesions through the analysis of dynamic vascular patterns (DVP).

Littoral cell angioma of the spleen.

We report for the first time on the contrast-enhanced ultrasound (CEUS) features of littoral cell angioma of the spleen (LCA). A patient presented with the incidental finding of splenomegaly which was investigated using modern ultrasound techniques. B-mode technique revealed heterogenous splenic parenchyma and small hypoechoic lesions up to 30 mm in size. Colour Doppler imaging revealed no specific vascularity. CEUS showed arterial hyper- and hypoenhancement with pronounced demarcation in the late phase. In an assumption of malignancy the lesions were biopsied using ultrasound guidance. Histology showed LCA. In this case report we discuss LCA in the light of new ultrasound techniques and present a review of the literature.

EFSUMB guidelines 2011: comments and illustrations.

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) introduced the first guidelines on the use of contrast-enhanced ultrasound (CEUS) in 2004. This EFSUMB document focused mainly on liver applications. However, new applications extending beyond the liver were subsequently developed. Therefore, in the update of the clinical recommendations on the use of CEUS by the EFSUMB, applications in other organs were also described and published in 2008. Increased interest in recent years in the CEUS technique and in the application of CEUS in novel fields has resulted in CEUS indications and applications for nearly all organ systems. As a result, the EFSUMB initiated a new update of the guidelines in 2011 to include this additional knowledge. Some of the indications are established, whereas others are preliminary. The latter indications are categorized as emergent CEUS applications since the available evidence is insufficient for general recommendation. This article focuses on comments, illustrations and examples of the application of CEUS in the pancreas, spleen, gastrointestinal tract, kidney, adrenals, lymph nodes, perineum, and hepatobiliary system. The potential for endoscopic ultrasound to highlight the importance of CEUS in the daily routine is also addressed.

Liver tumor characterization--review of the literature.

Multicenter trials to assess contrast-enhanced ultrasound (CEUS) for the imaging of focal liver lesions (FLLs) have included more than 1000 patients. This article reviews the published literature pertaining to these trials to determine the role of CEUS in the characterization of FLL.

EFSUMB guidelines 2011: comment on emergent indications and visions.

The focus of this article is the emergent and potential indications of contrast-enhanced ultrasound (CEUS). Emergent applications of CEUS techniques include extravascular and intracavitary contrast-enhanced ultrasound, quantitative assessment of microvascular circulation for tumor response assessment, and tumor characterization using dynamic contrast-enhanced ultrasound (DCE-US). Potential indications for microbubble agents include novel molecular imaging and drug and gene delivery techniques, which have been successfully tested in animal models. "Comments and Illustrations of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Non-Liver Guidelines 2011" which focus more on established applications are published in the same supplement to Ultraschall in der Medizin (European Journal of Ultrasound).

Contrast-enhanced ultrasound (CEUS) in the diagnostic algorithm of hepatocellular and cholangiocellular carcinoma, comments on the AASLD guidelines.

Contrast-enhanced ultrasound (CEUS) has long been present in important guidelines and recommendations for the diagnostic work-up of focal liver lesions in patients with cirrhosis. These guidelines have included the guidelines of the American Association for the Study of Liver Diseases (AASLD) 2005, the Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma, the recommendations of the Japanese Society of Hepatology, and the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 (in preparation). Recently, the AASLD removed CEUS from their guidelines in part because of the perceived possibility of false-positive hepatocellular carcinoma (HCC) diagnosis in patients with intrahepatic cholangiocarcinoma (ICC), and in part because CEUS is not available in the USA. This latter factor means that published results are not entirely applicable to a North American population. The present manuscript discusses the diagnostic algorithm of hepatocellular carcinoma and provides information on the differential diagnosis between HCC and ICC.

Imaging of gastrointestinal stromal tumours with modern ultrasound techniques - a pictorial essay.

Gastrointestinal stromal tumours (GIST) are rare tumours of the gastrointestinal tract. Dealing with these tumours requires a profound knowledge of the nature of the lesions and their malignant potentials. Modern ultrasound techniques provide the necessary tools to give the clinician the information he needs to diagnose and treat the patient. This article reviews the actual pathophysiological knowledge of GIST and provides a broad spectrum of ultrasound findings to introduce the reader into modern ultrasound investigation methods of subepithelial tumours. It covers the transcutaneous as well as the endoscopic ultrasound approach. Different conditions of GIST like the low risk or high risk form as well as the metastatic form will be discussed in diagnosis and treatment with plenty of examples. Special attention is paid to contrast-enhanced ultrasound techniques and elastography from the transcutaneous as well as the endoscopic route. Other diagnostic methods like CT, MRI and PET CT are additionally reviewed and their role in clinical practice is compared with that of ultrasound. The aim of the article is to introduce the reader into the new ultrasound techniques and special diagnostic behaviour of GIST and outline clinical pathways to deal correctly with different stages of the disease.

Biliary papillomatosis and new ultrasound imaging modalities.

Biliary papillomatosis (BP) is a rare disorder of the biliary tract with a significant risk of malignant transformation and a high recurrence rate after operation due to the diffuse distribution of the disease. Preoperative diagnosis is difficult also by reason of the low sensitivity and specificity of conventional ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERC) and positron emission tomography (PET). Therefore, the introduction of new diagnostic imaging methods is of importance to improve the preoperative diagnosis of this originally as benign described disease which is reflected in the term of "benign papillomatosis of the biliary tree". The present review summarizes the literature and discusses new sonographic imaging techniques including contrast-enhanced ultrasound (CEUS), contrast-enhanced low mechanical endoscopic ultrasound (CELMI-EUS) and endoscopic ultrasound elastography.