Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.

PURPOSE: PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. METHODS: Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. RESULTS: Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort (n = 6). No significant reduction in affected tissue volume was observed (mean -4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). CONCLUSION: Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.

The infragluteal fold: An appraisal by MRI combined with an anatomic study.

PURPOSE: The gluteal region is a key element of beauty balance and sexual appearance. However, there is no clear anatomical description of the infragluteal fold, nor any classification exists allowing standardizing treatment of this area in case of jeopardisation. The purpose of this study was to perform an anatomical description of the infragluteal fold (IGF) matching radiological and anatomical findings in describing specifically raise of the fibrous component at the bone level. METHODS: Six volunteers (three males and three females) underwent an MRI scan (Siemens Aera® 1.5 T) of the pelvic region. T1 Vibe Morpho T2, Sag Space 3D, and Millimetric slices were performed in order to obtain a more detailed selection of the gluteal landmark. Trabecular connective tissue of the region was analyzed using Horos® ROI (region of interest) segmentation function. Four fresh cadavers (two males, two females, accounting for 8 hemipelvis) were dissected in order to compare the radiological findings. RESULTS: The infragluteal fold is a connectival fibrous band extending from the ramus of the ischium (but not involving the ischial tuberosity, for a length of 21 mm ± 2 and 21 mm ± 3), the apex of the sacrum (for a length of 13 ± 2 and 11 mm ± 2), and the coccyx (for a length of 19 mm ± 2 and 20 mm ± 2, all measures referring to volunteers and cadavers, respectively) reaching superficially the dermis of the medial one-third of the cutaneous fold. No significant difference was found between volunteer and cadaver group in MRI measurement of bony origins, or between MRI and cadaveric dissection measurements. CONCLUSION: Knowledge of this structure will define novel surgical techniques in infragluteal fold restoration.

Endovascular stenting for chronic femoro-iliac venous obstructive disease: Clinical efficacy and short-term outcomes.

PURPOSE: To report the clinical efficacy and mid-term outcomes of endovascular treatment in patients with chronic, symptomatic, post-thrombotic femoro-iliac venous obstruction. MATERIALS AND METHODS: Forty-two patients with post-thrombotic syndrome (PTS) presenting with femoro-iliac venous obstructive lesions treated in our institution by endovascular approach between March 2012 and October 2017 were retrospectively included. There were 27 women and 15 men with a mean age of 47.3±17 (SD) years (range: 22-86 years). Procedure included first venous recanalization, then pre-dilatation and self-expandable metallic stenting of the narrowed or occluded iliac and/or femoral veins. Severity of PTS and quality of life were assessed at baseline and 3 months after the intervention respectively, using Villalta score and Chronic Venous Insufficiency Questionnaire (CIVIQ-20) scale. Imaging follow-up evaluation of stent patency was based on the results of duplex Doppler ultrasound and computed tomography. RESULTS: Immediate technical success was achieved in 41/42 (97.6%) patients, without any major complications. Primary patency, primary assisted patency and secondary patency at the end of the median imaging follow-up of 18.1 months (IQR, 9.7-34.4) were achieved in 29/42 (66.7%) patients, 33/42 (78.6%) patients and 37/42 (88.1%) patients, respectively. Median Villalta and CIVIQ-20 scores decreased from 14 (IQR, 10-19) and 57 (IQR, 39-72) at baseline, respectively, to 5 (IQR, 2-9) and 30 (IQR, 24-50) 3 months after the procedure, respectively (P<0.0001), showing significant decrease in the severity of PTS and improvement in the quality of life. The multiple linear regression model showed that both baseline Villalta and CIVIQ-20 scores ([95% CI: -7.80-3.79; P<0.0001] and [95% CI: 0.07-0.20; P<0.0001], respectively), age (95% CI: 0.04-0.19; P=0.002) and stenting expanse (95% CI: 0.97-5.65; P=0.006) were independent variables related to Villalta gain. Baseline Villalta (95% CI: 0.89-2.23; P<0.0001) was the single independent variable related to CIVIQ-20 gain. CONCLUSION: This study confirms the high clinical efficacy and favorable mid-term outcomes of endovascular stenting in patients with chronic symptomatic femoro-iliac venous obstructive lesions.

Computer-aided diagnosis system for characterizing ISUP grade≥2 prostate cancers at multiparametric MRI: A cross-vendor evaluation.

PURPOSE: To assess the performance of a computer-aided diagnosis (CADx) system trained at characterizing International Society of Urological Pathology (ISUP) grade≥2 peripheral zone (PZ) prostate cancers on multiparametric magnetic resonance imaging (mpMRI) examinations from a different institution and acquired on different scanners than those used for the training database. PATIENTS AND METHODS: Preoperative mpMRIs of 74 men (median age, 65.7 years) treated by prostatectomy between 2014 and 2017 were retrospectively selected. One radiologist outlined suspicious lesions and scored them using Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2); their CADx score was calculated using a classifier trained on an independent database of 106 patients treated by prostatectomy in another institution. The lesions' nature was assessed by comparison with prostatectomy whole-mounts. Diagnostic accuracy was estimated with areas under receiver operating characteristic curves (AUCs). Sensitivity and specificity were calculated using a CADx threshold (≥0.21) that yielded 95% sensitivity in the training database, and a PI-RADSv2≥3 threshold. RESULTS: A total of 127 lesions (PZ, n=104; transition zone [TZ], n=23) were described. In PZ, CADx and PI-RADSv2 scores had similar AUCs for characterizing ISUP grade≥2 cancers (0.78 [95% confidence interval (CI): 0.69-0.87] vs. 0.74 [95%CI: 0.62-0.82], respectively) (P=0.59). Sensitivity and specificity were respectively 89% (95%CI: 82-97%) and 42% (95%CI: 26-58%) for the CADx score, and 97% (95%CI: 93-100%) and 37% (95%CI: 22-52%) for the PI-RADSv2 score. In TZ, both scores showed poor specificity. CONCLUSION: In this external cohort, the CADx and PI-RADSv2 scores showed similar performances in characterizing ISUP grade≥2 cancers.

Reliability and reproducibility of the American Association for the Surgery of Trauma scaling for renal injury and impact on radiologic follow-up.

INTRODUCTION: The American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) is the most used classification for renal trauma. It determines the radiologic monitoring, only recommended for high-grade injuries. The aim of this study was to assess the subjectivity of AAST scaling and its impact on short-term follow-up. METHODS: We retrospectively reviewed all patients with blunt renal injuries admitted at a university hospital between 2010 and 2015. Computed Tomography (CT) scan were analyzed and injuries graded according to AAST OIS independently by a senior radiologist, a senior urologist who was blind to clinical data and a resident urologist. Grading disagreements were analyzed collegially to obtain a final rating. The agreement of AAST scaling was evaluated through the Cohen's Kappa coefficient. RESULTS: Ninety-seven patients had 101 renal injuries: low grade in 58.4% (11.9% grade I, 17.8% grade II, 28.7% grade III) and high grade in 41.6% of cases (23.6% grade IV and 17.8% grade V). The agreement was fair with Kappa coefficient at 0.36. The agreement was moderate in severity sub-division analysis (low or high grade): Kappa coefficient at 0.59. There was a disagreement in 49.5% between the senior urologist's and the senior radiologist's ratings. Those differences brought to a severity group change and radiologic follow-up modification in 34% (n=17). CONCLUSION: AAST OIS for renal trauma suffers from subjectivity but is improved by severity sub-group analysis. This subjectivity influences the radiologic follow-up but could be reduced by collegiate rating. LEVEL OF EVIDENCE: 4.

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with Type 2 diabetes.

AIMS: To evaluate the application of the recently proposed recommendations by the European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity for the diagnosis, treatment and follow-up of non-alcoholic fatty liver disease in people with Type 2 diabetes. METHODS: A total of 179 people with Type 2 diabetes were included in this study. Liver fat content (assessed using proton magnetic resonance spectroscopy), fatty liver index score, non-alcoholic fatty liver disease fibrosis score, and SteatoTest and FibroTest scores were determined. RESULTS: According to proton magnetic resonance spectroscopy, 68.7% of participants had steatosis (liver fat content >5.5%). The application of the guidelines using several combinations (fatty liver index + non-alcoholic fatty liver disease fibrosis scores, Steatotest + FibroTest scores, proton magnetic resonance spectroscopy + non-alcoholic fatty liver disease fibrosis score, proton magnetic resonance spectroscopy + FibroTest) resulted in a referral to a liver clinic for 33.5-84.9% people with Type 2 diabetes. CONCLUSIONS: The application of these new algorithms for the diagnosis, and follow-up of non-alcoholic fatty liver disease would lead to an excessive number of people with Type 2 diabetes being referred to a liver clinic. We suggest that new clinical and/or biological biomarkers of steatosis and fibrosis be specifically validated in people with Type 2 diabetes.

Imaging of Von Meyenburg complexes.

Von Meyenburg complexes, or biliary hamartomas, are frequently incidentally detected. They are usually easy to characterize with magnetic resonance imaging. However, in some occasions they are difficult to differentiate from other liver lesions, in particular from small liver metastases. Von Meyenburg complexes are developmental malformations of the ductal plate. They can be found in association with Caroli disease and Caroli syndrome. Like other ductal plate malformations, Von Meyenburg complexes associated with cholangiocarcinoma have been described and their relationship has been established. This review provides an update on the etiopathogenesis of Von Meyenburg complexes, illustrates the imaging features on ultrasound, CT and MRI of this condition and discusses the most common diagnostic pitfalls. The relationships between Von Meyenburg complexes and the various ductal plate malformations and the most recent literature data regarding the relationships between Von Meyenburg complexes and cholangiocarcinoma are presented.

Transcatheter arterial embolization for acute nonvariceal upper gastrointestinal bleeding: Indications, techniques and outcomes.

Over the past three decades, transcatheter arterial embolization has become the first-line therapy for the management of acute nonvariceal upper gastrointestinal bleeding that is refractory to endoscopic hemostasis. Advances in catheter-based techniques and newer embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the treatment of bleeding for a variety of indications. Transcatheter arterial embolization is a fast, safe, and effective minimally invasive alternative to surgery, when endoscopic treatment fails to control acute bleeding from the upper gastrointestinal tract. This article describes the role of arterial embolization in the management of acute nonvariceal upper gastrointestinal bleeding and summarizes the literature evidence on the outcomes of endovascular therapy in such a setting.

Transjugular intrahepatic portosystemic shunt for acute variceal gastrointestinal bleeding: Indications, techniques and outcomes.

Acute variceal bleeding is a life-threatening condition that requires a multidisciplinary approach for effective therapy. The transjugular intrahepatic portosystemic shunt (TIPS) procedure is a minimally invasive image-guided intervention used for secondary prevention of bleeding and as salvage therapy in acute bleeding. Emergency TIPS should be considered early in patients with refractory variceal bleeding once medical treatment and endoscopic sclerotherapy fail, before the clinical condition worsens. Furthermore, admission to specialized centers is mandatory in such a setting and regional protocols are essential to be organized effectively. This procedure involves establishment of a direct pathway between the hepatic veins and the portal veins to decompress the portal venous hypertension that is the source of the patient's bleeding. The procedure is technically challenging, especially in critically ill patients, and has a mortality of 30%-50% in the emergency setting, but has an effectiveness greater than 90% in controlling bleeding from gastro-esophageal varices. This review focuses on the role of TIPS in the setting of variceal bleeding, with emphasis on current indications and techniques for TIPS creation, TIPS clinical outcomes, and the role of adjuvant embolization of varices.

Current role of transcatheter arterial embolization for bladder and prostate hemorrhage.

Intractable hematuria from the bladder or the prostate can be life-threatening and its management remains a difficult clinical problem. Severe bleeding can arise as a result of radiation cystitis, bladder carcinoma, cyclophosphamide-induced cystitis, severe infection, transurethral resection of the prostate and prostate cancer. When irrigation of the bladder through a three-way catheter and fulguration of the bleeding lesions fail to stop the hematuria, a life-threatening situation can develop, when blood transfusion fails to keep pace with the rate of blood loss. Patients with massive uncontrollable hematuria are often elderly and unfit for cystectomy as a treatment. Many urologists have had to manage this difficult problem, and several different treatments have been attempted and described, with varying degrees of success. Transcatheter arterial embolization of the vesical or prostatic arteries is occasionally indicated in these patients when all other measures have failed. There is limited published experience with this procedure, but success in 90% of patients is reported when the vesical or prostatic arteries can be identified. The aim of this review is to describe the current place of transcatheter arterial embolization in the management of severe bladder or prostate bleeding after failed conservative therapy, and to review its efficacy and morbidity.

Multidisciplinary management strategies for acute non-variceal upper gastrointestinal bleeding.

BACKGROUND: The modern management of acute non-variceal upper gastrointestinal bleeding is centred on endoscopy, with recourse to interventional radiology and surgery in refractory cases. The appropriate use of intervention to optimize outcomes is reviewed. METHODS: A literature search was undertaken of PubMed and the Cochrane Central Register of Controlled Trials between January 1990 and April 2013 using validated search terms (with restrictions) relevant to upper gastrointestinal bleeding. RESULTS: Appropriate and adequate resuscitation, and risk stratification using validated scores should be initiated at diagnosis. Coagulopathy should be corrected along with blood transfusions, aiming for an international normalized ratio of less than 2·5 to proceed with possible endoscopic haemostasis and a haemoglobin level of 70 g/l (excluding patients with severe bleeding or ischaemia). Prokinetics and proton pump inhibitors (PPIs) can be administered while awaiting endoscopy, although they do not affect rebleeding, surgery or mortality rates. Endoscopic haemostasis using thermal or mechanical therapies alone or in combination with injection should be used in all patients with high-risk stigmata (Forrest I-IIb) within 24 h of presentation (possibly within 12 h if there is severe bleeding), followed by a 72-h intravenous infusion of PPI that has been shown to decrease further rebleeding, surgery and mortality. A second attempt at endoscopic haemostasis is generally made in patients with rebleeding. Uncontrolled bleeding should be treated with targeted or empirical transcatheter arterial embolization. Surgical intervention is required in the event of failure of endoscopic and radiological measures. Secondary PPI prophylaxis when indicated and Helicobacter pylori eradication are necessary to decrease recurrent bleeding, keeping in mind the increased false-negative testing rates in the setting of acute bleeding. CONCLUSION: An evidence-based approach with multidisciplinary collaboration is required to optimize outcomes of patients presenting with acute non-variceal upper gastrointestinal bleeding.

Interventional radiology for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20% of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive locoregional image-guided interventional managements including intra-arterial and percutaneous ablative therapies. In this paper, we review these interventional approaches. Catheter-based therapies include embolotherapy/chemotherapy-based treatments (such as transarterial chemoembolization, bland embolization, transcatheter arterial chemoinfusion, and chemoembolization with drug-eluting beads), and radiotherapy-based treatments (such as radioembolization with yttrium-90 and injection of iodine-131-labeled lipiodol). Ablative therapeutic approaches include chemical therapies (such as ethanol or acetic acid injection), and thermal therapies (such as radiofrequency ablation, laser induced thermotherapy, microwave ablation, cryoablation, and high-intensity focused ultrasound ablation). Each method has its advantages and drawbacks. As a result of the technical development of locoregional approaches for HCC during the recent decades, the range of combined interventional therapies has been continuously extended. In this article, an evidence-based approach is used to review the current role of interventional radiology in the management of unresectable HCC.

Packing technique for endovascular coil embolisation of peripheral arterial pseudo-aneurysms with preservation of the parent artery: safety, efficacy and outcomes.

OBJECTIVES: To evaluate the endovascular treatment of pseudo-aneurysms (PAs) with super-selective coil embolisation using the 3D packing technique. DESIGN: Retrospective study of consecutive patients in one academic centre. MATERIALS: From 2002 to 2009, 16 patients (mean age 51.6 years, range 24-82) underwent PA sac packing with coils. Four patients were asymptomatic, nine had PA rupture, and three had other symptoms. Lesion location was as follows: splenic artery (8), carotid artery (2), hepatic artery (2), superior mesenteric artery (1), cystic artery (1), uterine artery (1), and hypogastric artery (1). METHODS: The sac was packed with 0.018-inch controlled-detachable microcoils, preserving the parent artery. Magnetic resonance angiography was done within 6 months, at 12 months then yearly. RESULTS: Technical success rate was 100%. Complete definitive PA exclusion was achieved with a single procedure in 15 (93.8%) patients. One patient with a secondary bleeding arterio-digestive fistula underwent successful surgery. No major complications or late recanalisations occurred during follow-up (mean, 24.7 months; range 6-49). CONCLUSIONS: Coil PA embolisation by 3D sac packing is safe and effective and may induce less morbidity than complete parent vessel occlusion, stent placement, or open surgery. This procedure should be used whenever possible, as it preserves parent artery patency.