Programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis in hepatocellular carcinoma: prognostic and therapeutic perspectives.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. There have been tremendous efforts in the development of therapeutic strategies in the last decades. As opposed to other cancer entities immunotherapy has just recently gained popularity in HCC. Among various immunotherapy approaches, programmed cell death protein-1 (PD-1), and its ligand programmed death receptor ligand-1 (PD-L1) axis became one of the most promising pathway of the decade. The scientific interest in PD-1/PD-L1 axis is definitely justified due to: ability to detect PD-L1 expression in patients that underwent resection for HCC with prognostic values; the role of serum PD-L1 as a tool to identify early recurrences and to monitor treatment outcome; PD-1/PDL1 is a highly targetable pathway, with possible predictive markers, and with high clinical applicability that might help us in selecting a subgroup of HCC patients who are most likely to benefit from PD-1/PD-L1 inhibitors. In this review we will first discuss the prognostic role of PD-1/PD-L1 as a bio-marker in various clinical scenarios. Afterwards we will critically analyse the recently published trials with PD-1/PD-L1 inhibitors in HCC either alone or in combination with other treatment modalities. The higher focus will be on clinical rather than preclinical studies. Nevertheless, the strengths and limits of PD-1/PD-L1 axis in both prognosis and therapy of HCC will be highlighted.

Clinical Impact and Safety of Anticoagulants for Portal Vein Thrombosis in Cirrhosis.

OBJECTIVES: Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy. METHODS: The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion. RESULTS: The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan-Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival (HR:0.30, CI:0.10-0.91, p = 0.014). The Child-Turcotte-Pugh classes B/C negatively influenced survival (hazard ratio, (HR):3.09, confidence interval (CI):1.14-8.36, p = 0.027 for Child-Turcotte-Pugh B and HR:9.27, CI:2.67-32.23, p < 0.001 for Child-Turcotte-Pugh C). Bleeding complications occurred in 22 (21.8%) untreated and 16 (19.7%) treated patients, but in only four cases was it judged to be related to the anticoagulant treatment. No death was reported as a consequence of the bleeding events. CONCLUSIONS: Anticoagulant treatment is a safe and effective treatment leading to partial or complete recanalization of the portal venous system in 56.8% of cases, improving the survival of patients with cirrhosis and PVT. Discontinuation of the therapy is associated with a high rate of PVT recurrence.

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.

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).

Percutaneous sclerotherapy of liver and renal cysts, comments on the EFSUMB guidelines.

Cystic lesions in the liver and kidneys are common incidental findings. They are generally benign and require no treatment. They can appear sporadically or as part of a syndrome, and are characterised by their anechoic structure and posterior enhancement in ultrasound imaging. Increased size, haemorrhage or infection of a cyst can lead to development of symptoms. Along with surgical options and laparoscopic cyst fenestration, ultrasound-guided sclerotherapy of symptomatic cysts represents an effective and safe minimally invasive treatment option.

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).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Short Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version/ short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Long Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version).

Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a prospective multicenter study of its usefulness in clinical practice.

PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS: CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patient's informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS: A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION: CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis.

Non-invasive biochemical markers are useful to distinguish between nonalcoholic steatohepatitis (NASH) and simple steatosis. The aim of this study was to test the diagnostic value of a panel of biomarkers derived from the pathophysiological events involved in the development of NASH. A total of 79 patients: 20 not-NASH and 59 NASH were included in the study. Definitive NASH was defined according to Kleiner's classification. In all subjects, parameters of the metabolic syndrome, insulin resistance (HOMA-IR), adiponectin, interleukin-6 (IL-6) and total cytokeratin-18 (M65 antigen) were determined. Univariate and multivariate analysis were used to identify independent predictors of NASH. In multivariate analysis three markers were independently predictors of NASH: adiponectin, IL-6 and M65 levels. In decreasing order, the independent predictors of NASH (NAS≥5) were M65 with an AUROC of 0.791, IL-6 with an AUROC of 0.727 and adiponectin with an AUROC of 0.709. The combination of two biomarkers yelded an AUROC of 0.828 for M65 and IL-6, 0.841 for adiponectin and M65 and 0.852 for adiponectin and IL-6. The best value was obtained by triple combination: adiponectin, M65 and IL-6 with and AUROC of 0.903, Sp=85.7% (PPV=94.2%) and Se=84.5% (NPV=66.7%). In conclusion, a novel pathophysiological - based panel of biomarkers combining total CK-18, IL-6 and adiponectin may be useful to predict NASH.

Intestinal obstruction secondary to appendiceal mucocele.

Few cases of intestinal obstruction complicating an appendiceal mucocele have been recorded. We report the case of a young woman who presented to the emergency room with diffusely abdominal pain, nausea, vomiting and disruption of bowel movements. Her abdomen was mildly distended and tympanic. A flat film of the abdomen revealed dilated small bowel loops with air-fluid levels suggestive of small bowel obstruction. She also had leukocytosis. An emergency operation was performed under the diagnosis of intestinal obstruction. The intraoperatory findings showed a tumoral appendiceal mass permeated into the ileum in two distinct points, causing an enteral stenosis. We performed an appendectomy "en bloc" with two enteral loop resections of the permeated ileum followed by two T-T enteral anastomoses. The pathologic examination revealed appendiceal mucinous cystadenoma. Postoperative course was favorable, the patient being discharged on the seventh postoperative day. Postoperative checks performed at 3, 6, 12 and 24 months (including colonoscopy) have not showed pathological changes.