Refining Liver Biopsy in Hepatocellular Carcinoma: An In-Depth Exploration of Shifting Diagnostic and Therapeutic Applications.

The field of hepatocellular carcinoma (HCC) has faced significant change on multiple levels in the past few years. The increasing emphasis on the various HCC phenotypes and the emergence of novel, specific therapies have slowly paved the way for a personalized approach to primary liver cancer. In this light, the role of percutaneous liver biopsy of focal lesions has shifted from a purely confirmatory method to a technique capable of providing an in-depth characterization of any nodule. Cancer subtype, gene expression, the mutational profile, and tissue biomarkers might soon become widely available through biopsy. However, indications, expectations, and techniques might suffer changes as the aim of the biopsy evolves from providing minimal proof of the disease to high-quality specimens for extensive analysis. Consequently, a revamped position of tissue biopsy is expected in HCC, following the reign of non-invasive imaging-only diagnosis. Moreover, given the advances in techniques that have recently reached the spotlight, such as liquid biopsy, concomitant use of all the available methods might gather just enough data to improve therapy selection and, ultimately, outcomes. The current review aims to discuss the changing role of liver biopsy and provide an evidence-based rationale for its use in the era of precision medicine in HCC.

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for patients with intrahepatic cholangiocarcinoma.

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case. From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome.

Multisystemic Inflammatory Syndrome in Children, A Disease with Too Many Faces: A Single-Center Experience.

BACKGROUND AND AIM: Multisystemic inflammatory syndrome in children (MIS-C) is a rare and severe condition associated with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection in children with onset approximately 4-6 weeks after infection. To date, the precise mechanism that causes MIS-C is not known and there are many questions related to the etiology, risk factors, and evolution of this syndrome. We aimed to describe the clinical manifestations, treatment methods, and disease evolution and analyze the main risk factors for MIS-C in children hospitalized in our clinic. MATERIAL AND METHODS: We performed a retrospective study including children with MIS-C followed-up in the 2nd Pediatric Clinic of the Emergency Clinical Hospital for Children Cluj-Napoca, Romania, for 13 months (November 2020-December 2021). RESULTS: We included in our cohort 34 children (mean age 6.8 ± 4.6 years) who met MIS-C criteria: high and prolonged fever associated with organ dysfunction (heart, lungs, kidneys, brain, skin, eyes, bone marrow or gastrointestinal organs), and autoantibodies and/or polymerase chain reaction positives for SARS-CoV-2. Nineteen patients (55.88%) had a severe form of the disease, with multiorgan failure and shock, and myocardial or respiratory failure. The number of organs affected in the severe forms was significantly higher (more than 6 in 73.70%) than in mild forms (2-3 in 60%). Cardiac dysfunction, hypoalbuminemia, hypertriglyceridemia and hyponatremia were more important in severe forms of MIS-C. These patients required respiratory support, resuscitation with fluid boluses, vasoactive drugs, or aggressive therapy. All patients with mild forms had fully recovered compared to 63.16% in severe forms. The others with severe forms developed long-term complications (dilation of the coronary arteries, premature ventricular contraction, or myocardial fibrosis). Two patients had an extremely severe evolution. One is still waiting for a heart transplant, and the other died (hemophagocytic lymphohistiocytosis syndrome with multiorgan failure). CONCLUSIONS: From mild to severe forms with multiorgan failure, shock, and many other complications, MIS-C represents a difficult challenge for pediatricians, who must be aware of the correct diagnosis and unpredictable, possibly severe evolution.

Pulmonary complications of portal hypertension: The overlooked decompensation.

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.

Novel approaches in search for biomarkers of cholangiocarcinoma.

Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

The added value of CEUS and ultrasound-guided biopsy in diagnosing an aggressive desmoplastic small round cell tumour of peritoneum in a young male. A case report.

Desmoplastic small round cell tumour (DSRCT) is a rare and highly aggressive mesenchymal neoplasm with poor prognosis that develops in male adolescents and young adults. We report the case of a 32-year-old male admitted with abdominal distension and ascites. An ultrasonography (US) scan showed multiple peritoneal masses with large ascites. The dominant mass had a hypervascular homogenous aspect at contrast-enhanced ultrasound with wash-out in the venous phase. Thoracoabdominal CT, performed for staging the disease, confirmed the US aspect. The US-guided percutaneous biopsy revealed DSRCT of the peritoneum. Chemotherapy was then started with minimal clinical improvement, increase in tumoral burden and death after three months. US and US-guided biopsy played an essential role in diagnosing this case. The aggressive course of the disease and seeding at paracentesis sites are the particularities of the presented case.

Contrast enhancement for ultrasound-guided interventions: when to use it and what to expect?

The use of contrast-enhanced ultrasonography (CEUS) has recently become synonymous with high-standard ultrasonography (US). From expanding the reach of US diagnostics to improving the precision of various invasive procedures, CEUS is rapidly becoming a standard in numerous niches. However, proficiency in CEUS comes with a cost, both from a learning curve and material standpoint, and as every growing field, lacks firm evidence and standardization. Therefore, in the current paper, we aim to provide an evidence-based review of available methods and to discuss the advantages and pitfalls of CEUS in interventional procedures, trying to provide strong evidence whenever available, or at least an educated expert opinion if data are lacking.

Ultrasound or Sectional Imaging Techniques as Screening Tools for Hepatocellular Carcinoma: Fall Forward or Move Forward?

Hepatocellular carcinoma (HCC) is probably the epitome of a screening target, with a well-defined high-risk population, accessible screening methods, and multiple curative-intent treatments available for early disease. Per major societies guideline consensus, biannual ultrasound (US) surveillance of the at-risk patients is the current standard of care worldwide. Yet, despite its documented success in the past decades, this standard is far from perfect. While the whole community is working to further tighten the knots, a worrying number of cases still slip through this safety net. Consequently, these patients lose their chance to a curative solution which leads to a high disease burden with disproportionate mortality. While US will probably remain the fundamental staple in the screening strategy, key questions are seeking better answers. How can its caveats be addressed, and the technique be improved? When are further steps needed? How to increase accuracy without giving up on accessibility? This narrative review discusses the place of US surveillance in the bigger HCC picture, trying to navigate through its strengths and limits based on the most recent available evidence.

Serum levels of soluble programmed death-ligand 1 (sPD-L1): A possible biomarker in predicting post-treatment outcomes in patients with early hepatocellular carcinoma.

BACKGROUND: There have been great advances in hepatocellular carcinoma management over the last years. However, there are still no prognostic biomarkers that can identify patients who will benefit the most from curative treatments. We aimed to investigate whether sPD-L1 levels measured before curative treatment is a prognostic biomarker of survival in patients with HCC. METHODS: HCC patients from a prospectively collected database were selected and soluble programmed death-ligand1(sPD-L1) levels were determined. The association of sPD-L1 levels and overall survival (OS) and disease-free survival (DFS) was assessed. RESULTS: One hundred twenty-one patients with HCC were included. The best cut-off value of sPD-L1 for both DFS and OS was 96 pg/mL. Patients with a high sPD-L1 value (>96 pg/mL) had a shorter disease free survival and OS (hazard ratio 5.42, 95% confidence interval 2.28-12.91, p < 0.001, and hazard ratio 9.67, 95% confidence interval 4.33-21.59, p < 0.001). High sPD-L1 levels were associated with mortality independently from other known survival predictors. We found a positive correlation between sPD-L1 and PD-L1 expression in cancer cells (p = 0.01). In 16 out of 38 patients, sPD-L1 levels decreased from baseline value on week 6 after treatment and in 22 out of 38 patients, sPD-L1 levels increased from the baseline value. However, fluctuations of sPD-L1 in time had no influence on survival (p = 0.148). CONCLUSION: We conclude that a high sPD-L1 level is a biomarkerfor a poor outcome in HCC. The predictive value of sPD-L1 levels for a successful anti-PD1/PD-L1 therapy should be investigated in the future.

Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma (HCC) we do have a far-reaching arsenal. Moreover, because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options-from surgery to immunotherapy trials-it leaves the clinician a wide range of options. The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies, discussing their advantages and flaws in comparison to the current standard of care. One particular combination therapy seems to be in the forefront: Transarterial chemoembolization plus ablation for medium-size non-resectable HCC (3-5 cm), which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B. Not only does it improve the outcome in contrast to each individual therapy, but it also seems to have similar results to surgery. Also, the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC. Although the path of combination therapies in HCC is still filled with uncertainty and caveats, in the following years the hepatology and oncology fields could witness an HCC guideline revolution.

Endoscopic or percutaneous biliary drainage in hilar cholangiocarcinoma: When and how?

Hilar cholangiocarcinoma (hCCA) is a primary liver tumor associated with a dim prognosis. The role of preoperative and palliative biliary drainage has long been debated. The most common techniques are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD); however, recently developed endoscopic ultrasound-assisted methods are gaining more atention. Selecting the best available method in any specific scenario is crucial, yet sometimes challenging. Thus, this review aimed to discuss the available techniques, indications, perks, pitfalls, and timing-related issues in the management of hCCA. In a preoperative setting, PTBD appears to have some advantages: low risk of postprocedural complications (namely cholangitis) and better priming for surgery. For palliative purposes, we propose ERCP/PTBD depending on the experience of the operators, but also on other factors: the level of bilirubin (if very high, rather PTBD), length of the stenosis and the presence of cholangitis (PTBD), ERCP failure, or altered biliary anatomy.

Microwave ablation in the treatment of liver tumors. A better tool or simply more power?

It has been a long time since tumor ablation was first tested in patients with liver cancer, especially hepatocellular carcinoma. Since than it has become a first line treatment modality for hepatocellular carcinoma. Over the years, the indications of thermal ablation have expanded to colorectal cancer liver metastases and intrahepatic cholangiocarcinoma as well. Together with the new indication for ablation, new ablation devices have been developed as well. Among them microwave ablation shows potential in replacing radiofrequency ablation as the preferred method of thermal ablation in liver cancer. The debate whether radiofrequency or microwave ablation should be the preferred method of treatment in patients with liver cancer remains open. The main purpose of this review is to offer some answers to the question: Microwave ablation in liver tumors: a better tool or simply more power? Various clinical scenarios will be analyzed including small, medium, and intermediate size hepatocellular carcinoma, colorectal cancer liver metastases and intrahepatic cholangiocarcinoma. Furthermore, the advantages, limitations, and technical considerations of MWA treatment will be provided also.

Percutaneous ultrasound guided radiofrequency and microwave ablation in the treatment of hepatic metastases. A monocentric initial experience.

AIM: Percutaneous radiofrequency (RFA) and microwave ablation (MWA) are currently the best treatment options forpatients with liver metastases (LM) who cannot undergo a liver resection procedure. Presently, few studies have evaluated theefficacy of tumor ablation in beginner's hands but none at all in hepatic metastasis. Our aim was to report the initial experiencewith ultrasound as a tool to guide tumor ablation in a low volume center with no experience in tumor ablation. MATERIAL AND METHODS: We conducted a retrospective cohort study, on a series of 61 patients who had undergone percutaneous US-guided ablations for 82 LM between 2010 and 2015. Long term outcome predictors were assessed using univariate and multivariate analysis. RESULTS: Complete ablation was achieved in 86.9% of cases (53/61). All MWA sessions (20/20) attained ablation margins >5mm, compared to 79% (49/62) for RFA sessions (p=0.031). Ablation time was significantly shorter for MWA, with a median duration of 10 minutes (range: 6-12) vs. 14 minutes (range: 10-19.5, p=0.003). There was no statistically significant difference in local tumor progression (LTP)-free survival rates between MWA and RFA (p=0.154). On univariate analysis, significant predictors for local recurrence were multiple metastases (p=0.013) and ablation margins <5 mm (p<.001), both retaining significance on multivariate analysis. Significant predictors for distant recurrence on both univariate and multivariate analysis were multiple metastases (p<0.001) and non-colorectal cancer metastases (p<0.05). CONCLUSION: A larger than 5 mm ablation size is critical for local tumor control. We favor the use of MWA due to its ability to achieve ablation in significantlyshorter times with less incomplete ablations.

Real-Time Contrast-Enhanced-Guided Biopsy Compared with Conventional Ultrasound-Guided Biopsy in the Diagnosis of Hepatic Tumors on a Background of Advanced Chronic Liver Disease: A Prospective, Randomized, Clinical Trial.

We aimed to compare contrast-enhanced-guided liver biopsy (CEUSLB) and ultrasound-guided liver biopsy (USLB) in the diagnosis of focal liver lesions (FLLs) developed on a background of advanced chronic liver disease (ACLD). Between 2011 and 2019, patients diagnosed with liver tumors on a background of ACLD were evaluated for inclusion in the study. Patients were randomly assigned to the CEUSLB or USLB group. In total, 144 patients were randomly assigned to either CEUSLB (n = 79) or USLB (n = 65). Overall, in the CEUSLB group, the sensitivity was significantly better (94.74% vs. 74.6%, respectively; p = 0.001). Both the fragment length of the biopsy specimen and the single puncture success rate were statistically higher in the CEUSLB group (p = 0.022 and p = 0.0006, respectively). There was no difference in terms of major or minor complications (p = 0.682). CEUSLB is a feasible technique that increases the diagnostic sensitivity for liver tumors developed in ACLD.

Prognostic Factors after Percutaneous Radiofrequency Ablation in the Treatment of Hepatocellular Carcinoma. Impact of Incomplete Ablation on Recurrence and Overall Survival Rates.

AIMS: To report on the long-term impact of tumor and non-tumor related parameters on local recurrence, distant recurrence and survival in patients with naïve or recurrent type hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA). METHODS: We performed 240 RFA sessions on 133 patients with 156 HCC nodules developed on a background of liver cirrhosis and analyzed the outcomes. RESULTS: Contrast-enhanced ultrasound performed one month after RFA showed complete ablation in 119 out of 133 (89.65%) patients. With a median follow-up of 46 months, 3-, 5- and 7-year survival rates were 61.7%, 35.7%, and 22.6%, respectively. Previous ethanol injection and histological grade were significantly related to local tumor progression. Child-Pugh class, incomplete ablation, histological grade, previous ethanol injection, alpha-fetoprotein level before the treatment, and local recurrence were all significantly related to distant recurrence. Multivariate analysis demonstrated that age, Child-Pugh class, distant recurrence and multiple incomplete ablations were significantly related to survival. CONCLUSION: Radiofrequency ablation could be locally curative for HCC, resulting in a survival longer than 7 years. Previous ethanol injection and incomplete ablations were strongly associated with poor outcomes.

What's new in musculoskeletal ultrasound in pediatric rheumatology?

Musculoskeletal ultrasound (MSUS) has become almost indispensable in the rheumatology settings nowadays, allowing early diagnosis, careful guidance during procedures such as joint injections and therapy monitoring. Nonetheless, the applicability of MSUS in pediatric population is still limited. Recently, a standardized MSUS examination procedure in pediatric patients with rheumatic diseases, definitions for synovitis and the sonographic features of joints in healthy children has been developed. Also, important data on age-related  vascularization and ossification of joints in children have been published. Much work still needs to be done in the field. As juvenile idiopathic arthritis seems to be the most common use of MSUS in pediatric rheumatology, specific definitions and assessment techniques for enthesitis, tenosynovitis, bone and cartilage damage in children are very much expected. In this article, we will review briefly the current evidence-based knowledge regarding MSUS potential applications in the pediatric rheumatology clinical practice, along with an overview of the recent information about US appearance of musculoskeletal structures in healthy children.

Evaluation of anti-cyclic citrullinated peptide antibodies may be beneficial in RF-negative juvenile idiopathic arthritis patients.

Despite the high diagnostic and prognostic performance in adult rheumatoid arthritis, the role of antibodies to cyclic citrullinated peptide (anti-CCP) in juvenile idiopathic arthritis (JIA) is controversial. Occurrence of anti-CCP was mainly seen in rheumatoid factor (RF)-positive polyarthritis patients. In the present study, our aim was to investigate the prevalence and significance of anti-CCP for subjects with JIA in our population. We evaluated anti-CCP reactivity in the sera of 70 patients with various subtypes of JIA in a prospective cohort study. Anti-CCP titres were correlated with the evolution of joint involvement and the presence of joint damage. Nine JIA patients were seropositive for anti-CCP with respect to the cut-off value of the test. In our cohort, 34 patients had a polyarticular joint disease, most of them being RF-negative (30/34, 88 %). All four RF-positive polyarthritis patients had high anti-CCP concentrations and an aggressive erosive disease. In the RF-negative JIA patients, anti-CCP reactivity was in lower titres but significantly associated with polyarticular joint involvement (p = 0.016) and also with the presence of joint damage (p < 0.001). Presence of anti-CCP, at both low and high concentration, was significantly associated with a more severe articular disease in our JIA patients. Investigating anti-CCP should clearly be taken into consideration even among patients with JIA subtypes other than RF-positive polyarthritis.

Prospective comparison between real time contrast enhanced and conventional ultrasound guidance in percutaneous biopsies of liver tumors.

AIMS: The performance of percutaneous echo-guided biopsy in the hepatic tumoral diagnosis is limited (90% sensitivity) by several factors, among which tumor characteristics (type, size, and location) play an important role. Contrast enhanced ultrasound guided percutaneous biopsy (CEUS-PLB) is a new developed technique aimed at increasing the accuracy of percutaneous biopsies. The objective of our study was to evaluate the feasibility and performance of CEUS as a guiding method in performing liver biopsy (PLB). MATERIAL AND METHODS: One hundred and seventy one patients with liver tumors referred to the ultrasound department for LB were prospectively included in the study. PLB was performed with CEUS guidance in 90 patients (46 in patients with and 44 in patients without liver cirrhosis), in the remaining 81 (37 in patients with liver cirrhosis and 44 in patients without) with conventional US guidance. The lesions in the CEUS -PLB group were larger than those in the US-LB group (mean diameter 7.73 cm vs. 6.11 cm, p>0.05). In both groups the lesions were further divided in: a) lesions on cirrhosis; b) poorly visualized tumors; c) large tumors (>6 cm); d) cystic tumors; e) recurrences after ablation; and f) portal vein thrombosis. RESULTS: Real time CEUS-PLB was technically successful in 84 of the 86 procedures (97.6% technical success rate). The rate of successful single puncture attempt in CEUS-PLB (43.02%) was higher than in the US-PLB group (23.4%) (p<0.05). The sensitivity of LB was significantly higher in the CEUS-PLB group than in the conventional US-LB group for all lesions (96.5% vs. 81.48%, p<0.05), for lesions on liver cirrhosis (95.2% vs. 75%, p<0.05), for large (> 6 cm) (97.8% vs. 82%, p<0.05), and for poorly visible lesions (100 vs. 66.6%, p=0.029). The patients with inconclusive pathological results after conventional guided LB were then biopsied with CEUS guidance. In all cases the final diagnosis could be established. One major complication occurred in each group (p>0.05). CONCLUSIONS: Percutaneous LB performed with CEUS guidance is a feasible and safe technique. It significantly improves the overall sensitivity of the procedure especially in patients with large lesions and in those poorly visualized on conventional ultrasound.

Primary complement and antibody deficiencies in autoimmune rheumatologic diseases with juvenile onset: a prospective study at two centers.

BACKGROUND: Our aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset. METHODS: A total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively. RESULTS: Our cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7%), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8%) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8%), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap). CONCLUSIONS: Our findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.

Contrast enhanced ultrasound of renal masses. A reappraisal of EFSUMB recommendations and possible emerging applications.

The main imagistic method for characterization of renal lesions is contrast enhanced computed tomography (CECT). Disadvantages of CECT are a contrast-induced nephropathy in patients with renal impairment, allergic reactions and high costs. Contrast-enhanced ultrasound (CEUS) evaluation of hepatic and non-hepatic lesions is a relatively new, but increasingly utilised, diagnostic method. In 2011 the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) updated the Guidelines and Recommendations on the Clinical Practice of CEUS and included in the recommendation the renal pathology. However, there are several possible new indications that have not been discussed (pyelocaliceal masses and renal vein thrombosis) and several issues that remain controversial such as the differentiation of benign and malignant tumours or the differentiation of lymphoma and metastasis. This study aims to review literature data, as well as reveal the latest findings in the field of renal CEUS.