Combining CEUS and ultrasound parameters in thyroid nodule and cancer diagnosis: a TIRADS-based evaluation.

Contrast-enhanced ultrasonography (CEUS) has been established as a diagnostic tool for assessing microvascularization, essential for understanding angiogenesis in neoplastic development. AIM: This study assesses the effectiveness of CEUS as a supplementary tool to TIRADS in enhancing the ultrasound-based diagnosis of thyroid cancer. METHODS AND MATERIALS: Over one year, 157 nodules in 133 patients, with predominantly solid thyroid nodules, were examined using ultrasound and CEUS and underwent thyroidectomy, allowing for a comparison of ultrasound findings with pathological reports. RESULTS: Thyroid cancer was identified in 31.21% (49/157) of cases. Significant CEUS high-risk features included inhomogeneous enhancement, enhancement defects, and complete hypoenhancement (AUC 0.818, 0.767, 0.864 respectively). Nodules exhibiting any of these features were classified as high-risk in CEUS. The diagnostic performance of TIRADS improved when combined with CEUS, with AUC increasing from 0.707 to 0.840 and improved sensitivity. CONCLUSION: The integration of CEUS with TIRADS significantly enhances the diagnostic accuracy and specificity in identifying thyroid cancer. This combination proves to be a more effective method for risk stratification and diagnosis, highlighting the value of CEUS as an adjunctive tool in thyroid cancer evaluation.

Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Identification of Microbial Species and Analysis of Antimicrobial Resistance Patterns in Acute Cholangitis Patients with Malignant and Benign Biliary Obstructions: A Comparative Study.

Background and Objectives: Acute cholangitis (AC) is still lethal if not treated promptly and effectively. Biliary drainage, also known as source control, has been acknowledged as the backbone treatment for patients with AC; nonetheless, antimicrobial therapy allows these patients to undergo non-emergent drainage procedures. This retrospective study aims to observe the bacterial species involved in AC and analyze the antimicrobial resistance patterns. Materials and Methods: Data were collected for four years, comparing patients with benign and malignant bile duct obstruction as an etiology for AC. A total of 262 patients were included in the study, with 124 cases of malignant obstruction and 138 cases of benign obstruction. Results: Positive bile culture was obtained in 192 (73.3%) patients with AC, with a higher rate among the benign group compared with malignant etiologies (55.7%.vs 44.3%). There was no significant difference between the Tokyo severity scores in the two study groups, identifying 34.7% cases of malignant obstruction with Tokyo Grade 1 (TG1) and 43.5% cases of TG1 among patients with benign obstruction. Similarly, there were no significant differences between the number of bacteria types identified in bile, most of them being monobacterial infections (19% in the TG1 group, 17% in the TG2 group, and 10% in the TG3 group). The most commonly identified microorganism in blood and bile cultures among both study groups was E. coli (46.7%), followed by Klebsiella spp. (36.0%) and Pseudomonas spp. (8.0%). Regarding antimicrobial resistance, it was observed that significantly more patients with malignant bile duct obstruction had a higher percentage of bacterial resistance for cefepime (33.3% vs. 11.7%, p-value = 0.0003), ceftazidime (36.5% vs. 14.5%, p-value = 0.0006), meropenem (15.4% vs. 3.6%, p-value = 0.0047), and imipenem (20.2% vs. 2.6%, p-value < 0.0001). Conclusions: The positive rate of biliary cultures is higher among patients with benign biliary obstruction, while the malignant etiology correlates with increased resistance to cefepime, ceftazidime, meropenem, and imipenem.

The role of elastography for liver fibrosis screening in alcoholic liver disease.

Non-invasive tests have been developed to determine the severity of liver disease in patients with alcohol use disorder (AUD). We aimed to assess the severity of liver steatosis and liver fibrosis (LF) in a cohort of patients with AUD using liver elastography and biological scores. MATERIALS AND METHODS: A prospective study was performed on 172 subjects, without previously known liver disease, with a positive AUDIT-C score, serum markers, and vibration-controlled transient elastography (VCTE) with Controlled Attenuation Parameter (CAP). RESULTS: From 172 subjects with positive AUDIT-C test, VCTE diagnosed advanced fibrosis (F3) in 13.9% (24/172) of the subjects and liver cirrhosis (F4) in 17.5% (30/172). Moderate and severe steatosis was found in 18.6% (32/172), respectively 52.3% (90/172). Significant correlations were found between liver stiffness and APRI (r=0.33, p=0.001), FIB-4(r=0.31, p=0.0012) and the age-platelet index (r=0.25, p=0.008). FIB-4 (p=0.01) and age-platelet index (p=0.03) were independently associated with the presence of advanced fibrosis. Age-platelet index (AUC- 0.82) performed significantly better than AST/ALT (AUC- 0.55) and APRI (AUC- 0.58) (p= 0.0001 and p= 0.0014, respectively), but no differences were found when compared to FIB-4 (AUC- 0.77) (p=0.35) for predicting advanced fibrosis. CONCLUSION: In conclusion, in a cohort of patients with AUD, 70.9% presented moderate and severe liver steatosis and 17.5% were newly diagnosed with liver cirrhosis.

Contrast-Enhanced Ultrasonography with Arrival Time Parametric Imaging as a Non-Invasive Diagnostic Tool for Liver Cirrhosis.

Liver biopsy is the gold standard method for staging liver fibrosis, but it is an invasive procedure that is associated with some complications. There are also non-invasive techniques for assessing liver fibrosis, such as elastography and biological tests, but these techniques can fail in detection or generate false measurements depending on the subject's condition. This study aimed to determine whether liver fibrosis can be evaluated using contrast-enhanced ultrasonography with arrival time parametric imaging using the ultrasound machine's parametric image software, the method being called (CEUS-PAT). CEUS-PAT was performed on each subject using SonoVue as a contrast agent, and images showing liver parenchyma and the right kidney on a single screen were used for analysis in parametric imaging, which was performed using the proprietary software of the ultrasound system. The ratio between the kidney and liver arrival times was calculated. The study included 64 predominantly male (56.3%) subjects, 37 cirrhotic patients, and 27 healthy volunteers, with a mean age of 58.98 ± 8.90 years. Significant differences were found between the liver cirrhosis and healthy groups regarding CEUS-PAT, 0.83 ± 0.09 vs. 0.49 ± 0.11, p < 0.0001. The correlation between CEUS-PAT and VCTE was r = 0.81. The optimal cut-off value for detecting liver cirrhosis was >0.7, with an AUC of 0.98, p < 0.001, Se = 89.19%, Sp = 100%, PPV = 100%, and NPV = 87.1%. We demonstrate that CEUS-PAT achieves excellent performance in diagnosing liver cirrhosis and is a fast method for diagnosing liver cirrhosis that can even be applied in situations where the use of other methods is excluded.

Usefulness of Imaging and Biological Tools for the Characterization of Portal Vein Thrombosis in Hepatocellular Carcinoma.

This study aims to evaluate the performance of contrast-enhanced ultrasound (CEUS) and biological tests to characterize portal vein thrombosis (PVT). We retrospectively analyzed 101 patients with PVT, liver cirrhosis, and hepatocellular carcinoma (HCC). In all patients, demographic, biologic, imaging, and endoscopic data were collected. All patients underwent CEUS and a second line imaging technique (CE-CT/MRI) to characterize PVT. Of the 101 cirrhotic subjects, 77 (76.2%) had HCC. CEUS had 98.6% sensitivity (Se) and 89.3% specificity (Sp) for the characterization of PVT type. A significant correlation was found between alpha-fetoprotein (AFP) levels and the PVT characterization at CEUS (r = 0.28, p = 0.0098) and CT/MRI (r = 0.3, p = 0.0057). Using the AFP rule-out cutoff values for HCC (AFP < 20 ng/dL), 78% of the subjects were correctly classified as having benign PVT, while 100% of the subjects were correctly classified as tumor-in-vein (TIV) when the rule-in cutoff value was used (AFP ≥ 200 ng/dL). Using multiple regression analysis, we obtained a score for classifying PVT. The PVT score performed better than CEUS (AUC­0.99 vs. AUC­0.93, p = 0.025) or AFP serum levels (AUC­0.99 vs. AUC­0.96, p = 0.047) for characterizing PVT. In conclusion, CEUS is a sensitive method for the characterization of PVT. The PVT score had the highest performance for PVT characterization.

Is There a Place for Elastography in the Diagnosis of Hepatocellular Carcinoma?

BACKGROUND AND AIMS: Elastography can provide information regarding tissue stiffness (TS). This study aimed to analyze the elastographic features of hepatocellular carcinoma (HCC) and the factors that influence intratumoral elastographic variability in patients with liver cirrhosis. METHODS: This prospective study included 115 patients with liver cirrhosis and hepatocellular carcinoma evaluated between June 2016-November 2019. A total of 88 HCC nodules visualized in conventional abdominal ultrasound (US) met the inclusion criteria and underwent elastographic evaluation. Elastographic measurements (EM) were performed in HCC and liver parenchyma using VTQ (Virtual Touch Quantification), a point shear wave elastography (pSWE) technique. In all patients, we performed contrast-enhanced ultrasound (CEUS), and the final diagnosis of HCC was established by contrast-enhanced-CT or contrast-enhanced-MRI. RESULTS: The mean VTQ values in HCCs were 2.16 ± 0.75 m/s. TS was significantly lower in HCCs than in the surrounding liver parenchyma 2.16 ± 0.75 m/s vs. 2.78 ± 0.92 (p < 0.001). We did not find significant differences between the first five and the last five EM, and the intra-observer reproducibility was excellent ICC: 0.902 (95% CI: 0.87-0.950). However, the tumor size, heterogeneity, and depth correlated with higher intralesional stiffness variability (p < 0.001). CONCLUSIONS: VTQ brings additional information for HCC characterization. Intra-observer reproducibility for both HCC and liver parenchyma was excellent. Knowing the stiffness of HCC's might endorse an algorithm-based approach towards focal liver lesions (FLLs) in liver cirrhosis.

Contrast-enhanced ultrasound algorithm (ACR CEUS LI-RADSv 2017)- a valuable tool for the noninvasive diagnosis of hepatocellular carcinoma in patients with chronic liver disease.

AIMS: to evaluate the accuracy of LR-5 category from the latest Contrast-Enhanced Ultrasound algorithm (ACR CEUS LI-RADSv 2017) for the noninvasive diagnosis of hepatocellular carcinoma (HCC), in a real-life cohort of high-risk patients. MATERIAL AND METHODS: We retrospectively re-analysed the CEUS studies of 464 focal liver lesions (FLL) in 382 patients at high-risk for HCC (liver cirrhosis of any aetiology, chronic B or C hepatitis with severe fibrosis) using the ACR CEUS LI-RADSv 2017 algorithm. CEUS LI-RADS categories used for the diagnosis of HCC were: CEUS LR-5 (definitely HCC) and CEUS LR-TIV (HCC with macrovascular invasion). Contrast-enhanced CT, contrast-enhanced MRI, or histology were used as diagnostic reference methods to evaluate the CEUS LI-RADS classification of the 464 lesions. RESULTS: According to the reference method, the 464 lesions were classified as follows: 359 HCCs, 68 non-HCC-non-malignant lesions and 37 non-HCC malignant lesions. The diagnostic accuracy of LR-5 category for the diagnosis of hepatocellular carcinoma was 76.9%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.9%, 94.3 %, 97.7% and 49.5%, respectively. CONCLUSIONS: LR-5 category from ACR CEUS LI-RADSv 2017 algorithm, has good sensitivity, excellent specificity, and PPV for the diagnosis of HCC. The HCC rate increases from LR-3 to LR-5.

Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis.

An increasing number of tumor markers have been discovered to have potential efficacy as diagnostic and prognostic tools in gastric cancer. We aimed to assess putative correlations between claudin 18.2 expression and pathological or prognosis features in patients with gastric cancer. MEDLINE, Web of Science, EBSCO, and ClinicalTrials.gov were used to search for relevant studies from their inception to 30 October 2020. Finally, a total of six articles were included in this meta-analysis. Review Manager 5 software was applied to examine the heterogeneity among the studies and to calculate the odds ratio with 95% CI by selecting corresponding models, in evaluating the strength of the relationship. Publication bias test was also conducted. No bias and no significant correlations were found between CLDN 18.2 and TNM stages, Lauren classification, HER2, grading, or overall survival. This meta-analysis expounded that the relationship with CLDN 18.2 and pathological features depends on the percentage of staining of tumor cells for which CLDN 18.2 is considered positive. Our pooled outcomes suggest that targeted therapy for CLDN 18.2 could be effective if certain criteria were established.

Ultrasound-Guided Attenuation Parameter (UGAP) for the quantification of liver steatosis using the Controlled Attenuation Parameter (CAP) as the reference method.

AIM: Nonalcoholic Fatty Liver Disease (NAFLD) is increasing in frequency in daily practice and evaluation of liver steatosis, fibrosis and inflammation severity are essential for prognosis assessment. The aim was to evaluate the usefulnessof a new liver steatosis quantification system - Ultrasound-Guided Attenuation Parameter (UGAP) from General Electric Healthcare, using Controlled Attenuation Parameter (CAP) as the reference method. MATERIAL AND METHOD: 179 consecutive subjects, in whom liver steatosis was assessed in the same session using UGAP, implemented on LOGIQ E10 system (GE Healthcare), and CAP (FibroScan, EchoSens). To discriminate between steatosis stages by CAP, we used the cut-offs recommended by the manufacturer: S1 (mild) - 230 dB/m, S2 (moderate) - 275 dB/m, S3 (severe) - 300 dB/m. RESULTS: We classified our cohort by means of CAP into the following groups: S0 (no steatosis): 48/176 (27.2%), S1 (mild): 56/176 (31.6%), S2 (moderate): 14/176 (7.3%) and S3 (severe): 59/176 (33.9%). The mean UGAP values increased with the steatosis grade and for each group were the following: S0: 198.3±25.7 dB/m, S1: 216.86±26.3 dB/m, S2: 237.79±26.3 dB/m, and S3: 270.8±31.62 dB/m respectively (p<0.001). A very good positive correlation was found between UGAP and CAP values (r=0.73, p<0.0001). The best cut-off values for predicting different grades of liver steatosis using CAP as the reference were: S1 - 192.5 dB/m (AUC 0.83); S2 - 231 dB/m (AUC 0.90) and S3 - 248 dB/m (AUC 0.91). CONCLUSION: UGAP seems to be a good method for liver steatosis quantification and correlates strongly with CAP values.

Virtual Touch Quantification using Acoustic Radiation Force Impulse Imaging Technology versus Transient Elastography for the Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B or C using Liver Biopsy as the Gold Standard.

AIMS: Our aim was to assess the diagnostic performance of transient elastography (TE) and Virtual Touch Quantification (VTQ), a point Shear Wave Elastography (pSWE) technique, using Acoustic Radiation Force Impulse (ARFI) technology, for liver fibrosis assessment, as compared to percutaneous liver biopsy (LB), in patients with chronic hepatitis B or C. METHODS: We analyzed 157 patients (80 with chronic hepatitis B and 77 with chronic hepatitis C) with reliable liver stiffness (LS) measurements, in whom we compared TE and VTQ to the LB performed during the same session (evaluated according to the Metavir scoring system: F0-F4). LS was assessed by TE (FibroScan, EchoSens, Paris, France) and VTQ using the Siemens Acuson S2000TM ultrasound system (Siemens AG, Erlangen, Germany). We defined reliable LS measurements as the median value of 10 measurements with an IQR/M <30% for both TE (obtained using the M probe) and VTQ. The areas under receiver operating characteristic curves (AUROCs) were used to assess the diagnostic performance of TE and VTQ. Correlation analysis determined the relationship between LSM values and liver histology. RESULTS: On LB 31 (19.7%) patients had no fibrosis, 35 (22.3%) had F1, 43 (27.4%) had F2, 28 (17.8%) had F3 and 20 (12.7%) had cirrhosis. The mean size of the liver specimen in LB was 27 mm. A strong, linear correlation (Spearman ρ=0.826; p<0.001) with 95% confidence interval for rho (0.769- 0.870), was found between the TE and VTQ measurements. By comparing the AUROC curves, TE and VTQ had similar predictive values for the presence of F≥1 Metavir: AUROC TE=0.876, AUROC VTQ=0.832, p=0.358, for F≥2 Metavir: AUROC TE=0.826, AUROC VTQ=0.862, p=0.313, for F≥3 Metavir: AUROC TE=0.907, AUROC VTQ=0.880, p=0.434 and for F=4 Metavir: AUROC TE=0.981, AUROC VTQ=0.974, p= 0.423. CONCLUSIONS: Both methods, TE and VTQ (pSWE) offer excellent diagnostic accuracy for liver fibrosis assessment in patients with chronic hepatitis B or C with similar performance.

Comparative study between four ultrasound Shear Waves Elastographic methods for liver fibrosis assessment.

AIMS: Non-invasive methods to assess the severity of chronic liver diseases have become more and more popular. The aim of our study was to evaluate the correlation of four Shear Waves Elastographic methods in a cohort of patients with chronic liver diseases of mixed etiologies and to compare their performances for liver fibrosis evaluation. MATERIAL AND METHODS:  A prospective study was conducted on 127 consecutive patients with chronic liver diseases of mixed etiologies. LS measurements were performed in all subjects, in one session, during the same day, by means of 4 elastographic methods: Transient Elastography (TE), Virtual Touch Quantification (VTQ), ElastPQ and 2D-SWE.SSI. The diagnosis accuracies of VTQ, ElastPQ, 2D-SWE.SSI were then compared using TE as reference method. RESULTS: Valid LS measurements by all four shear waves ultrasound elastographic methods were obtained in 116/127 subjects with VTQ, in 108/127 subjects with 2D-SWE.SSI, in 111/127 with TE and in 109/127 with ElastPQ, so the final analysis included 82/127 subjects (64.5%). A good and significant correlation was found between all 4 elastographic methods. The diagnostic accuracy of VTQ, 2D-SWE.SSI and ElastPQ for the diagnosis of significant and severe fibrosis (F2/F3), and liver cirrhosis were similar for all elastographic techniques: VTQ vs 2D-SWE.SSI vs ElastPQ: 84.1% vs 85.3% vs. 84% (p>0.05); 93.9% vs 94% vs 94% (p>0.05). CONCLUSION: considering TE as the reference method for liver fibrosis evaluation, VTQ, ElastPQ, and 2D-SWE.SSI obtained similar accuracies for diagnosing at least significant fibrosis (F≥2) and liver cirrhosis.