Two patterns of contrast-enhanced ultrasonography with Sonazoid<Superscript>®</Superscript> in spontaneous rupture of hepatocellular carcinoma: a report of four cases

Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Detecting active bleeding is critical. Color Doppler and contrast-enhanced ultrasonography (CEUS) with Levovist^® are reported to be useful for detecting active bleeding. A few reports have described using Sonazoid^® to detect bleeding in ruptured HCC. This report describes two distinctive patterns of bleeding from ruptured HCC observed in CEUS with Sonazoid^®. Four patients with suspected HCC rupture were examined by gray-scale ultrasonography (US) and then CEUS with Sonazoid^®. Two patterns of bleeding were observed with CEUS: jet-like extravasation (n = 2) and bubble leakage (n = 2). While contrast-enhanced computed tomography and angiography revealed active bleeding in only one patient, CEUS detected active bleeding and enabled the bleeding site to be estimated in all patients. Transcatheter arterial embolization was performed based on the findings of CEUS, and hemostasis was achieved in all patients. CEUS using Sonazoid^® could demonstrate active bleeding as two patterns, and these findings enabled us to detect the rupture site of HCC more confidently than with other modalities.     

Predictive value of time–intensity curves obtained with contrast-enhanced ultrasonography (CEUS) in the follow-up of 30 patients with Crohn's disease

Objectives

CEUS can provide accurate quantitative estimates of intestinal wall microvascularization in Crohn''s disease. We hypothesized that inflammation of the intestinal wall is correlated not with the amount of wall vascularization (study of vascularization patterns, SVP) but with the degree of wall flow during a period of time (time–intensity study, TIS). Our objective was to discover whether CEUS SPV and/or CEUS-TIS reflect(s) vascular inflammation of the intestinal wall and display(s) correlation with clinical activity of the disease at the time of the examination (T0) or at the 3- and 6-month follow-up (T3, T6).

Materials and methods

30 patients with Crohn''s disease (12 men, 18 women, mean age: 41.96 years; treatment: 5-ASA (n = 8), steroids (n = 13), anti-TNF (n = 7), azathioprine (n = 2) were studied with CEUS SPV and CEUS-TIS and followed for at least 6 months. The sonographic examinations were performed with SonoVue (BR1, Bracco) and a dedicated scanner (TECHNOS MPX, Esaote) equipped with software for calculation of time–intensity curves. Four vascular patterns (1: vascularization of the entire wall; 2: vascularization of >50% of the wall; 3: flow exclusively within the submucosal layer; 4: no signal). The semiquantitative analysis consisted in measurement of the area under the curve (AUC) (cut-off between active and inactive disease, 15), mean intesnity (IMA) (cut-off = 10). Each examination (180 s) was digitally recorded and analyzed.

Results

T0: cDAI <150 in 22 pts; cDAI > 150 in 8; T3: 22 pts. with cDAI<150, 8 with cDAI >150. At T0 CEUS SPV and CEUS-TIS both displayed low specificity, diagnostic accuracy, and negative predictive values (p = ns). At T0, CEUS SPV produced 8 true positives (TP), 15 true negatives (TN), 8 false positives (FP), 0 false negative (FN) (sensitivity: 100%; specificity: 68.2%; diagnostic accuracy: 69.5%; Positive predictive value (PPV): 100%; negative predictive value (NPV: 53.3%), and CEUS-TIS produced 6 TP, 18 TN, 4 FP, 2 FN (sensitivity 75%; specificity: 81.8%; diagnostic accuracy: 75%; PPV: 60%; NPV: 90%). At T3, CEUS SPV produced 8 TP, 12 TN, 7 FP, 3 FN (sensitivity: 72.7%; specificity: 63.2%; diagnostic accuracy: 50%; PPV: 53.3%; NPV: 80%), and CEUS SIT produced the following results: 10 TP, 19 TN, 0 FP, 1 FN (sensitivity: 90,9%; specificity: 100%; diagnostic accuracy: 96,5%; PPV: 100%; NPV: 95%).At T3 CEUS-SVP displayed low sensitivity and low diagnostic accuracy, whereas SIT was able to predict clinical activity during follow-up in all but one case (which showed reactivation after 6 months) (p = 0.001)

Conclusion

CEUS-TIS alone was found to reflect vascular inflammation of the intestinal wall in Crohn''s disease and predicted clinical activity during follow-up.     

Application of contrast-enhanced ultrasonography after radiofrequency ablation for renal cell carcinoma: is it sufficient for assessment of therapeutic response?

Purpose

To assess the efficacy of contrast-enhanced ultrasonography (CEUS) with Sonovue in the evaluation of therapeutic response to radiofrequency ablation (RFA) of renal cell carcinoma (RCC).

Materials and methods

In a recent 3?years, 63 patients (mean age, 60?years; range 26?C81?years) with 64 RCCs were treated by RFA. The lesions had a diameter between 1.8 and 9.8?cm (average diameter, 3.1?cm). The indications for RFA treatment included chronic renal insufficiency (n?=?10), presence of solitary kidney (n?=3), bilateral renal carcinoma (BRCC) (n?=2), advanced age (n?=12), significant medical comorbidity (n?=29) or refusal of conventional therapy (n?=7). Tumors were treated by laparoscopy-assisted (n?=41), open surgical (n?=18) or percutaneous US guidance (n?=4). Follow-up CEUS and contrast-enhanced CT were performed 1?month after treatment to assess the necrotic area. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor.

Results

On the 1-month CEUS and CT imaging after RFA, 62 of 64 tumors (96.9%) were successfully ablated with one session, and residual tumors were found in two RCCs. One of the two tumors was subjected to additional RFA treatment. We could not obtain a complete ablation in the other tumor of a patient with solitary kidney. The diagnostic concordance between the CEUS and 1-month follow-up CT was 100%. Sixty-one patients survived in the follow-up phase which ranged from 2 to 34?months. One patient with solitary kidney died of systemic disease progression and one patient was lost to follow-up. Of the 61 tumors without residual on both CT and CEUS after RFA, four had suspicious findings of recurrence on follow-up CEUS, and two of them were confirmed by subsequent CT examination. With CT as the reference imaging procedure in the assessment of renal tumor ablation, the sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for detecting recurrence during follow-up were 100%, 96.6%, 50%, and 100%.

Conclusion

Despite its limitation of false-positive value, CEUS is potentially effective in assessing the therapeutic response to RFA of RCC.     

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.

     

A novel, label-free immunosensor for the detection of α-fetoprotein using functionalised gold nanoparticles

Background and objectives

Novel immunoassay methods based on electrochemical sensors have been developed, but most of these immunosensors are unsuitable for clinical detection because their preparation requires complicated chemical procedures and because their detection sensitivity is restricted. In order to develop a highly sensitive, label-free amperometric sensor for immunoassays, we synthesised novel, functionalised gold nanoparticles (SV-GNP) by covalently capping the surface of gold nanoparticles (GNP) with 1,1′-bis-(2-mercapto)-4,4′-bipyridinium dibromide, a kind of sulfhyrdryl viologen (SV).

Design and methods

We fabricated an immunosensor in a multi-step fashion, by first coating the SV-GNP onto a glassy carbon electrode surface; the resulting electrode core could then adsorb a suitable antibody in a second step to afford the desired immunosensor. α-fetoprotein (AFP) was used as a model analyte in this work.

Results

The anti-AFP/SV-GNP-modified electrode was sensitive to AFP with a linear relationship between 1.25 and 200 ng/mL and a correlation coefficient of 0.9983; the detection limit at a signal to noise ratio of 3 was 0.23 ng/mL under optimal conditions. In addition, the proposed immunosensor exhibited good sensitivity, selectivity, stability and long-term maintenance of bioactivity.

Conclusion

The described immunosensor preparation and immunoassay methods offer promise for label-free, simple, and cost-effective analysis of biological samples.     

Combined SPIO–gadolinium magnetic resonance imaging in cirrhotic patients: negative predictive value and role in screening for hepatocellular carcinoma

BACKGROUND: The objective of our study was to assess the negative predictive value (NPV) of double-contrast MRI (DC-MRI) with SPIO and gadolinium, and to determine the role of DC-MRI in screening for hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: We retrospectively included 160 DC-MRI scans done as second-line investigations in 119 patients with cirrhosis over a 25-month period. Two radiologists independently classified the MRI scans as strongly suggesting HCC (HCC Group), showing benign nodules (benign nodules Group), showing no nodules (no-nodules Group) or indeterminate; they assigned a diagnostic confidence score (DCS) using a 0-10 scale. The reference standard was histology or results of follow-up investigations. Mean follow-up was 16.9 months (12-28 months). RESULTS: The radiologists disagreed for two scans (kappa = 0.98). Of 112 scans [benign nodules Group (n = 32) and no-nodules Group (n = 80)], 11 were excluded (3 patients lost to follow-up and 8 who died with no known cancer) while a HCC was detected during follow-up in 8 patients, yielding a NPV of 92% (93/101) (95% confidence interval, 85%-97%). The DCS was in the 4-6 range (indicating uncertainty) for only 6 (3.75%) scans. CONCLUSIONS: DC-MRI is reliable and reproducible. Its high NPV suggests a role as a second-line investigation after ultrasonography, for HCC screening.     

Is there a role for liver transplantation in the treatment of hepatocellular carcinoma in non-cirrhotic liver?

Whether liver transplantation (LT) plays a role in the treatment of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver (NCL) is a matter of debate. The recommendations for LT in this setting are extremely fragile and less well-defined than for cirrhosis-associated HCC. All reports of LT for NCL-HCC revealed that long-term outcomes of these patients are poor, and these dismal figures are justified by the advanced tumor stage at the time of LT, suggesting the presence of systemic micrometastatic disease. The decision-making regarding LT for NCL-HCC is difficult, since specific selection criteria are scarce, and basically the potential candidates are those with unresectable only-liver tumor at admission, or unresectable intrahepatic recurrence post-resection. Besides the surgical aspects regarding the tumor resectability, other phenotypic and genetic characteristics of the tumor should be considered for the indication of LT in this scenario. The present minireview aims to discuss and analyze the last series of LT for NCL-HCC, in order to help clinicians in the decision-making process regarding the role of LT in NCL-HCC treatment.     

The value of PIVKA-Ⅱ versus AFP for the diagnosis and detection of postoperative changes in hepatocellular carcinoma

ObjectiveTo explore the diagnostic value of abnormal prothrombin Ⅱ (PIVKA-Ⅱ) and alpha-fetoprotein (AFP) in primary hepatocellular carcinoma (HCC).MethodsFrom 2018 0.01 to 2020.01, there were 158 patients with primary liver cancer caused by chronic hepatitis B (male 116, women 42) and 62 patients with chronic hepatitis B (male 34, female 28). The levels of serum PIVKA-Ⅱ and AFP were measured, and the results were statistically analyzed.ResultsThe value of PIVKA-Ⅱin liver cancer group was distinctly higher than that in chronic viral hepatitis B group, the difference is statistically significant (P ​< ​0.05). So does the value of AFP. Draw the subject working characteristic curve (ROC curve), the area under the curve of AFP and PIVKA-Ⅱ is 0.799 and 0.836, and that of the combination of AFP and PIVKA-Ⅱ is 0.854, the sensitivity is 57.6%,68.4%,72.2%,respectively, the specificity is 93.5%, 98.4%, 96.8%, respectively. After operation or interventional therapy, the value of PIVKA-Ⅱ in liver cancer group was clearly lower than that before treatment, and the difference was statistically significant.ConclusionIn the diagnostic value of primary liver cancer, PIVKA-II combined with AFP is higher than PIVKA-II, while AFP has the lowest benefit. We also find that PIVKA-II has higher disease monitoring value than AFP.     

Contrast-enhanced ultrasonography using Sonazoid® is useful for diagnosis of malignant ovarian tumors: comparison with Doppler ultrasound

Purpose

The purpose of this study was to assess the usefulness of Sonazoid^®-enhanced ultrasonography (US) in the diagnosis of ovarian cancer in comparison with Doppler US.

Methods

Twenty-five ovarian tumor patients who were scheduled to undergo surgery were recruited for this study. The day before the operation, each patient was evaluated with color and power Doppler and baseline US during intravenous infusion of Sonazoid. Each lesion was classified as “benign” or “malignant” on the basis of specific criteria for a Doppler signal or Sonazoid-enhanced pattern. The reference standard was the histology of surgically removed adnexal tumors.

Results

Twenty patients were diagnosed with malignant tumors (invasive cancer, n = 15; metastatic cancer, n = 1; borderline tumor, n = 4), and the remaining five were diagnosed with benign tumors. Sonazoid-enhanced US correctly depicted the presence or absence of intratumoral blood flow in all patients with an accuracy of 92 %. Color Doppler ultrasound depicted the malignancies with an accuracy of 64 %, and power Doppler ultrasound depicted them with an accuracy of 76 %.

Conclusion

Our study suggests that Sonazoid-enhanced US is superior to conventional color Doppler US for the diagnosis of malignant ovarian tumors, but not to power Doppler US. The data and their interpretation in our study should be taken with some degree of caution because of the small number of subjects. Further studies involving a larger sample size would be needed to confirm these findings.     

Does iodine concentration affect the diagnostic efficacy of biphasic spiral CT in patients with hepatocellular carcinoma?

Background We investigated the effect of iodinated contrast medium concentration on increased neoplastic lesion enhancement and its direct relation to diagnostic efficacy in biphasic spiral computed tomography for detection of hepatocellular carcinoma.Methods A pilot, single-center, randomized, double-blind, crossover, comparative study was performed and included 22 participants. Each patient underwent two separate biphasic contrast-enhanced spiral computed tomographic examinations. Scans were performed with iomeprol containing 400 (iomeprol 400) or 300 (iomeprol 300) mg of iodine per milliliter (Iomeron, Bracco Imaging SpA, Milan, Italy) with a 2- to 12-day window scan; patients were given an equal total dose of 45 g of iodine at a fixed injection rate of 4 mL/s. Comparison included assessment of quantitative and qualitative parameters.Results Lesion density and lesion-to-liver contrast increased more markedly with the higher concentration of contrast medium during the arterial phase (p = 0.0016 and 0.0005, respectively). There was no significant difference in any parameter between the two concentrations during the portal phase. Number of lesions detected during the arterial phase increased from 37 with iomeprol 300 to 42 with iomeprol 400; in the portal phase, the respective numbers were 34 and 36.Conclusion Even though a small number of patients was examined, our study suggests that, in patients with cirrhosis, an increased concentration of iodine improves liver-to-lesion contrast and may improve the detection of hepatocellular carcinoma.     

Blood oxygen level–dependent functional magnetic resonance imaging can evaluate the efficiency of transcatheter arterial chemoembolization in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is among the most common malignant tumors worldwide, and transcatheter arterial chemoembolization (TACE) technology has become the first-line treatment for advanced HCC. Another important, recently developed technique is blood oxygen level–dependent functional magnetic resonance imaging (BOLD-fMRI), which utilizes hemoglobin as an endogenous contrast agent and measures deoxygenated hemoglobin content by sampling the oxygen content of tissues, thus reflecting the hemodynamics and pathophysiologic changes in body organs. Currently this technology is being used in patients with liver tumors; that is, it serves as an important tool in follow-up after TACE. The present paper summarizes these developments.     

Reference change values for lens culinaris agglutinin-reactive α-fetoprotein and des-γ-carboxy prothrombin in patients with chronic hepatitis C

Abstract Background: Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3) and des-γ-carboxy prothrombin (DCP) have been routinely used as serological tumor markers of hepatocellular carcinoma (HCC) for surveillance. The aims of this study were: (i) to determine the biological variation of AFP-L3 and DCP in patients with chronic hepatitis C; and (ii) to calculate the reference change values (RCVs) of AFP-L3 and DCP. Methods: Ten patients with cirrhosis due to hepatitis C virus (HCV) infection and without HCC were enrolled in the study. Serum samples were collected at 14-day intervals, and 10 samples in total were obtained for each patient. AFP-L3 and DCP levels were measured by microchip capillary electrophoresis and liquid-phase binding assay. Intra-individual (CVI) and inter-individual (CVG) biological variations and RCVs were estimated from the data generated. Results: The CVI was 29.0% for AFP-L3 and 24.6% for DCP, and CVG was 63.5% for AFP-L3 and 40.4% for DCP. The RCVs for AFP-L3 and DCP were 68.3% and 58.5%, respectively. Conclusions: Increases in values for AFP-L3 and DCP within 68.3% and 58.5% may be biological variations. Clinician should take these variations into consideration for the management of patients with HCV infection under surveillance of HCC.     

Evaluation of α-iduronidase in dried blood spots is an accurate tool for mucopolysaccharidosis I diagnosis

Background: Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the α‐L ‐iduronidase (IDUA), which leads to the accumulation of glycosaminoglycans in lysosomes. MPS I patients present a spectrum ranging from a severe to an attenuated phenotype. Once clinical suspicion is present, diagnosis of MPS I can be performed by enzyme activity determination and/or molecular analysis. The aim of this study was to establish a reference interval value to IDUA activity using a dried blood spots (DBS) assay and to evaluate whether this assay could be a secure tool to diagnose MPS I patients. Results: IDUA activity range on HV DBS samples were 1.40–7.78 µmol/l blood/hr. Regarding the validation group, 11 of the 36 individuals clinically suspected of MPS I had the diagnosis confirmed by DBS and reference assay (leukocytes). When we considered the new proposed cutoff value of 1.5 µmol/l blood/hr, the sensitivity, specificity, and predictive values were 100%. Conclusions: Our results strongly suggest that the determination of IDUA activity using a DBS assay is a secure tool for MPS I diagnosis. However, it is extremely important to assure that all recommendations for collection, transport, and storage are correctly followed to guarantee the quality of the samples. J. Clin. Lab. Anal. 25:251–254, 2011. © 2011 Wiley‐Liss, Inc.     

A new ultrasonographic technique for diagnosing deep venous insufficiency—imaging and functional evaluation of venous valves by ultrasonography with improved resolution

This is to demonstrate a new 2D-ultrasonographic technique which enabled clear resolution of deformed valves, visualization of venous reflux and quantitation of valve incompetence. In a 59-year-old Japanese female patient, ultrasonography was done using Aplio, Toshiba Medical Systems Co., Japan, equipped with 8 MHz linear probe capable of differential tissue harmonic imaging to diagnose the cause of her leg edema. Venous ultrasonography using this device at the popliteal venous valve in this patient demonstrated clear view of deformed venous valve and valve separation at one end of valvular agger while the other part of the valve is closed. Color Doppler failed to show venous reflux due to its low velocity. However, the appearance and disappearance of a thrombus-like echo could be imaged using 2D-ultrasonography. In addition, we were able to demonstrate the time-course change of valve opening and closing, and quantitate the valve incompetence using M-mode ultrasonography.     

Does hyperbaric oxygen enhance the effect of photodynamic therapy in patients with advanced esophageal carcinoma? A clinical pilot study

BACKGROUND AND STUDY AIMS: Experimental studies have shown that the cytotoxicity of porphyrins and related substances is mediated mainly by singlet oxygen and that hypoxic cells are less affected by porphyrins and light. In a clinical pilot study we assessed the use of photodynamic therapy (PDT) under hyperbaric oxygen (HBO), compared with PDT under normobaric conditions, in patients with advanced esophageal carcinoma. PATIENTS AND METHODS: After diagnostic work-up and staging, photosensitization in all patients was carried out using hematoporphyrine derivate (HpD) (2 mg/kg bodyweight 48 hours prior to PDT). We then applied light at 630 nm (KTP-Nd: YAG laser with DYE box) at dose of 300 J/cm, delivered by a fiber with a radial light-diffusing cylinder (length 1 cm), inserted through the biopsy channel of the endoscope. Of the patients, 14 (12 with stage III cancers, and two with stage IV cancers) were treated by PDT alone, and 17 patients (15 with stage III cancers, and two with stage IV cancers) received PDT under HBO at a level of 2 absolute atmospheric pressures (ATA). Transcutaneous PO2 levels of 500-750 mm Hg under HBO, compared with transcutaneous PO2 levels of 60-75 mm Hg under normobaric conditions, were measured. RESULTS: Improvements regarding dysphagia and stenosis diameter were obtained in both treatment arms with no significant differences (P = 0.36 and 0.14, respectively). The tumor length also decreased in both groups and showed a significant difference in favour of the PDT/ HBO group (P = 0.002). Kaplan-Meier statistics showed median overall survival for the PDT group and the PDT/HBO group as 7.0 and 12 months respectively. The 12-month survival rate was 28.6% for the PDT group and 41.2% for the PDT/HBO group. Logrank test showed a difference in survival in favor of the PDT/HBO group (P = 0.059). No major treatment-related complication occurred, and the 30-day mortality rate was 0%. CONCLUSIONS: Combined PDT/HBO represents a new approach in the treatment of esophageal cancer which, in this pilot study, appears to have enhanced the efficiency of PDT.