BACKGROUND & AIMS:The transjugular (TJ) technique is recommended for the simultaneous evaluation of portal hypertension and hepatic fibrosis, with the hepatic venous pressure gradient (HVPG) and liver biopsy (LB), respectively. Unfortunately, technical challenges have restricted access to HVPG, and TJ LB is often of suboptimal quality. Endoscopic ultrasound (EUS) is a novel approach capable of obtaining portal pressure gradient (PPG) and LB. Our aim was to compare EUS-guided PPG LB with TJ HVPG LB. METHODS:Patients with chronic liver disease simultaneously evaluated for portal hypertension and liver fibrosis at the McGill University Health Centre were randomly assigned to EUS-guided PPG LB or TJ HVPG LB. The primary endpoint was the combination of adequate LB (guideline recommendation: ≥25 mm total length and ≥11 complete portal tracts) and reliable HVPG/PPG (expert consensus: 2 measures within ≤1 mm Hg). Secondary endpoints assessed technical success, LB quality, HVPG/PPG reliability, patient satisfaction, and adverse events. Intention-to-treat analyses were conducted. RESULTS:Fifty-eight patients were randomized; 29 were EUS and 29 were TJ. Technical success was 90.0% for EUS and 96.6% for TJ (relative risk [RR], 0.93; 95% confidence interval [CI], 0.81-1.07). Combined adequate LB and reliable HVPG/PPG was 82.8% for EUS and 41.4% for TJ (RR, 2.00; 95% CI, 1.26-3.18). Proportion of adequate LB was 93.1% for EUS and 41.4% for TJ (RR, 2.25; 95% CI, 1.44-3.51). Proportion of reliable HVPG/PPG was 89.7% for EUS and 58.6% for TJ (RR, 1.53; 95% CI, 1.10-2.13).We found no between-group difference in adverse events. CONCLUSIONS:EUS is superior to TJ for simultaneous acquisition of adequate LB and reliable PPG, suggesting that it has an important role in evaluating chronic liver diseases. CLINICALTRIALS:gov, Number: NCT05118308.

INTRODUCTION:Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are respiratory conditions requiring regular chest radiography (CXR) surveillance to monitor pulmonary disease. However, CXR is insensitive for lung disease in CF and PCD. Lung ultrasound (LU) is a radiation-free alternative showing good correlation with severity of lung disease in CF but has not been studied in PCD. METHOD:Standardized, six-zone LU studies and CXR were performed on a convenience sample of children with PCD or CF during a single visit when well. LU studies were graded using the LU scoring system, while CXR studies received a modified Chrispin-Norman score. Scores were correlated with clinical outcomes. RESULT:Data from 30 patients with PCD and 30 with CF (median age PCD 11.5 years, CF 9.1 years) with overall mild pulmonary disease (PCD median FEV1 90% predicted, CF FEV1 100%) were analyzed. LU abnormalities appear in 11/30 (36%) patients with PCD and 9/30 (30%) with CF. Sensitivity, specificity, positive predictive, and negative predictive values for abnormal LU compared to the gold standard of CXR are 42%, 61%, 42%, and 61% in PCD, and 44%, 81%, 50%, and 77% in CF, respectively. Correlation between LU and CXR scores are poor for both diseases (PCD r = -0.1288, p = 0.4977; CF r = 0.0343, p = 0.8571), and LU score does not correlate with clinical outcomes in PCD. CONCLUSION:The correlation of LU findings with CXR surveillance studies is poor in patients with mild disease burdens from PCD or CF, and LU scores do not correlate with clinical outcomes in PCD.

Rationale: Imatinib is used in the treatment of Philadelphia chromosome positive (Ph+) leukemias and has been reported to have a direct effect on bone physiology. Presentation: To report on a child with Ph+ acute lymphoblastic leukemia who presented with bilateral flank pain and gross hematuria. Diagnosis: She was diagnosed with obstructive kidney stones 101 days after commencing daily oral imatinib. Stone analysis revealed the presence of calcium phosphate. Interventions and outcome: The patient passed the stones spontaneously with medical therapy that included the use of thiazide, allopurinol, and potassium citrate, but she required temporary insertion of a double-J stent to relieve an obstruction. Novel findings: Imatinib inhibits receptor tyrosine kinases and stimulates the flux of calcium from the extracellular fluid into bone, resulting in hypocalcemia with a compensatory rise in parathyroid hormone that may result in phosphaturia and the formation of calcium phosphate stones. Given that kidney stones are rare events in children, we believe that monitoring for kidney stone formation needs to be performed in children receiving imatinib.

Urinary fistulas are usually managed with diversion, and persistent fistulas may require nephrectomy. For refractory cases in adults, rare reports have described percutaneous glues as an alternative to nephrectomy. We present the case of a child with persistent urinary leak after partial nephrectomy for recurrent microabscesses. In order to spare the child nephrectomy, the fistula was treated percutaneously with the application of cyanoacrylate glue and a vascular occlusion plug. This is the first report of percutaneous glue treatment with an adjunct vascular occlusion device for a urinary leak, and the first report of percutaneous management of a pediatric urinary fistula.

DICER1 syndrome is caused by germline pathogenic mutations in the DICER1 gene. Multinodular goiter (MNG) is a common clinical feature of DICER1 syndrome in children and adults. The aim of this study was to determine the ultrasound (US) characteristics of MNG in patients with DICER1 syndrome. This retrospective study evaluated thyroid US in patients with DICER1 germline mutations ( DICER1 mut+) performed between 2011 and 2018 at a single center by the same pediatric endocrinologist, and the images were re-examined by an independent pediatric radiologist from another academic center. Patients < 18 years with DICER1 mut+ and DICER1 mut+ parents without previous thyroidectomy were included. Ultrasound phenotypes of MNG in the setting of DICER1 mutations were compared with known US features of thyroid malignancy. Thirteen DICER1 mut+ patients were identified (10 children, 3 adults). Three children had a normal thyroid US; therefore, thyroid abnormalities were assessed in seven children and three adults. In both children and adults, multiple (≥ 3) mixed (cystic/solid) nodules predominated with single cystic, single cystic septated and single solid nodules, occasionally with a “spoke-like” presentation. All solid lesions were isoechogenic, and in only one with multiple solid nodules, intranodular blood flow on power/color Doppler was observed. Remarkably, macrocalcifications were present in all three adults. The spectrum of ultrasonographic findings of MNG in DICER1 mut+ patients is characteristic and largely distinct from typical features of thyroid malignancy and therefore should inform physicians performing thyroid US of the possible presence of underlying DICER1 syndrome.

Transhepatic duodenal stent placement may be a solution when endoscopy fails or when duodenal and biliary stents are needed simultaneously. This approach is usually not considered as an option when the duodenal stent must be deployed across the ampulla of Vater. The authors present a series of 10 patients who underwent a novel transhepatic technique to place a duodenal stent across the ampulla of Vater by establishing a wire scaffold from the liver toward the jejunum and then curving back on itself retrogradely through the duodenal tumor and out the mouth. Technical success was 90% with no associated mortality.

A large hepatic mixed echoic mass occupying the left fetal abdomen was identified at 266/7 weeks. The mass showed peripheral and internal vascularity. Other ultrasound findings included edema of the fetal head and face, macrosomia, shortened long bones, abnormal posture of hands, small stomach, polyhydramnios and biventricular hypertrophy. Fetal magnetic resonance imaging confirmed a hypervascular mass replacing the lateral left hepatic lobe, suggestive of a congenital hemangioma. The fetus was delivered by cesarean section at 282/7 weeks. The baby was stabilized at day 3 of life, and underwent successful selective tumor embolization. The baby remained stable for 3 days, then deteriorated with a progressive thickening of the myocardium. The child then passed away on day 11 from severe progressive hypertrophic cardiomyopathy, with almost complete obliteration of the left ventricular cavity; an autopsy was declined. Postnatal investigations reported a de novo heterozygous pathogenic HRAS variant (NM_005343.3(HRAS): c.35_36 delinsTT, p.Gly21Val), previously reported in 8 cases associated with the early, lethal form of Costello syndrome.

Background Image-guided procedures for treatment of liver diseases can be painful and require heavy sedation of the patient. Local-regional nerve blocks improve pain control and reduce oversedation risks, but there are no documented liver-specific nerve blocks. Purpose To develop a safe and technically simple liver-specific nerve block. Materials and Methods Between March 2017 and October 2019, three cadavers were dissected to evaluate the hepatic hilar anatomy. The hepatic hilar nerves were targeted with transhepatic placement of a needle adjacent to the main portal vein, under US guidance, and evaluated with use of an injection of methylene blue. A hepatic nerve block, using similar technique and 0.25% bupivacaine, was offered to patients undergoing liver tumoral ablation. In a prospective pilot study, 12 patients who received the nerve block were compared with a control group regarding complications, safety, pain scores, and intraoperative opioid requirement. Student t tests were used to compare the groups' characteristics, and Mann-Whitney U tests were used for the measured outcomes. Results Cadaver results confirmed that the hepatic nerves coursing in the hepatic hilum can be targeted with US for injection of anesthetic agents, with adequate spread of injected methylene blue around the nerves in the hepatic hilar perivascular space. The 12 participants (mean age ± standard deviation, 66 years ± 13; eight men) who received a hepatic hilar block before liver thermal ablations demonstrated reduced pain compared with a control group of 12 participants (mean age, 63 years ± 15; eight men) who received only intravenous sedation. Participants who received the nerve block had a lower mean visual analog scale score for pain than the control group (3.9 ± 2.4 vs 7.0 ± 2.8, respectively; P = .01) and decreased need for intraprocedural fentanyl (mean dose, 152 μg ± 78.0 vs 235.4 μg ± 58.2, respectively; P = .01). No major complications occurred in the hepatic hilar nerve block group. Conclusion A dedicated hepatic hilar nerve block with 0.25% bupivacaine can be safely performed to provide anesthesia during liver tumoral ablation. © RSNA, 2021.

Abstract Germline mutations in DICER1 cause a pleiotropic susceptibility syndrome characterized by the development of pediatric or early-onset tumors including pleuropulmonary blastoma, Wilms tumors, pineoblastomas, multinodular goiter (MNG) and thyroid cancers. Somatic mutations in the other two microprocessors DROSHA and DGCR8 have been found in Wilms Tumors and pineoblastomas. We present here two families with peripheral schwannomatosis and thyroid tumors carrying a germline variant c.1552G>A;p.E518K in DGCR8. Family one had six affected members with early-onset MNG and five of them developed schwannomatosis. All five members were heterozygous for the variant. One of the carriers had also been diagnosed with a choroid plexus papilloma at 7 years old. The common second event in all tumors tested was the loss of chromosome 22 at the somatic level. In family two, a 35-year-old male was diagnosed with a peripheral schwannoma at the age of 12. Since then, he has developed seven extra peripheral schwannomas (one of which was an ancient schwannoma) and papillary thyroid cancer. DGCR8 lies on chromosome 22q, adjacent to the three schwannoma genes: LZTR1, SMARCB1 and NF2. The variant, c.1552G>A;p.E518K localizes to the first RNA-binding domain of DGCR8 and structural modelling predicts that it abolishes proper binding of RNA. It is also a hotspot somatic mutation in Wilms tumors. Using miRNA profiling, we show that this variant disrupts global microRNA production and DGCR8 mutated tumors show a specific miRNA profile different from DGCR8 wild type tumors. These findings reinforce DGCR8 as a novel susceptibility gene for schwannomatosis and thyroid tumors.

This detailed genetic and molecular analysis of a three-generation family reveals a new form of autosomal dominant tumor susceptibility syndrome entitled familial multinodular goiter (MNG) with schwannomatosis. Biallelic alterations of the DGCR8 gene were found in all affected patients: First, all patients harbored the same heterozygous germline mutation p.E518K. Secondly, all thyroid nodules and all schwannomas analyzed from the patients showed somatic loss of the whole chromosome 22 in addition to the p.E518K germline mutation, resulting in loss of heterozygosity. DGCR8 is key element of the canonical microRNA production pathway by forming a trimeric nuclear complex called microprocessor. The biallelic alteration of DGCR8 at the tumor tissue levels caused disrupted microprocessor function, resulting in reduced precursor and mature microRNA expression due to disrupted cleavage of precursor microRNA from primary RNA.

Establishment of long-term central venous access imposes the risk of procedural adverse events (air embolism, pneumothorax, accidental arterial cannulation of the great vessels, tricuspid valve damage and cardiac tamponade) as well as the risk of increased morbidity and mortality due to catheter related blood stream infections, vessel stenosis, deep vein thrombosis and the often high risk anaesthetic management of syndromic children. This narrative review aims to provide a historical and clinical background for the development and use of CVADs (central venous access devices), origin and management of the most common complications (catheter related thrombosis, infections and persistent withdrawal occlusion) and present the reader with an update on the "why, what, where, who and how" in paediatric long-term central venous access. Finally, we will present the reader with a clinical method for applying a retrograde inserted tunnelled and cuffed catheter using the left brachiocephalic vein access.

Mesenchymal hamartoma of the liver (MHL) is a benign tumor affecting children that is characterized by a primitive myxoid stroma with cystically dilated bile ducts. Alterations involving chromosome 19q13 are a recurrent underlying cause of MHL; these alterations activate the chromosome 19 microRNA cluster (C19MC). Other cases remain unexplained. We describe two children with MHLs that harbored germline DICER1 pathogenic variants. Analysis of tumor tissue from one of the children revealed two DICER1 "hits." Mutations in DICER1 dysregulate microRNAs, mimicking the effect of the activation of C19MC. Our data suggest that MHL is a new phenotype of DICER1 syndrome.

BACKGROUND. DICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions. Other susceptibility genes for familial forms of MNG likely exist. METHODS. Whole-exome sequencing of a kindred with early-onset MNG and schwannomatosis was followed by investigation of germline pathogenic variants that fully segregated with the disease. Genome-wide analyses were performed on 13 tissue samples from familial and nonfamilial DGCR8-E518K-positive tumors, including MNG, schwannomas, papillary thyroid cancers (PTCs), and Wilms tumors. miRNA profiles of 4 tissue types were compared, and sequencing of miRNA, pre-miRNA, and mRNA was performed in a subset of 9 schwannomas, 4 of which harbor DGCR8-E518K. RESULTS. We identified c.1552G>A;p.E518K in DGCR8, a microprocessor component located in 22q, in the kindred. The variant identified is a somatic hotspot in Wilms tumors and has been identified in 2 PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the DGCR8 locus, was found in all 13 samples harboring c.1552G>A;p. E518K. miRNA profiling of PTCs, MNG, schwannomas, and Wilms tumors revealed a common profile among E518K hemizygous tumors. In vitro cleavage demonstrated improper processing of pre-miRNA by DGCR8-E518K. MicroRNA and RNA profiling show that this variant disrupts precursor microRNA production, impacting populations of canonical microRNAs and mirtrons. CONCLUSION. We identified DGCR8 as the cause of an unreported autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter with schwannomatosis.

Purpose To evaluate the effectiveness of superior hypogastric nerve block (SHNB) in reducing narcotic use after uterine artery embolization (UAE). Materials and Methods This study was a prospective, randomized, double-blind, parallel clinical trial in patients referred to a tertiary care university teaching hospital for UAE. Forty-four participants were enrolled (mean age, 46 years; range, 32-56 years). No consenting patient was excluded. All participants were randomized 1:1 to undergo either a sham procedure or SHNB. There were 22 participants in each group. One participant was lost to follow-up regarding home survey results. Use of narcotics and antiemetics was recorded in-hospital. Pain scores were recorded at home for 10 days with use of a visual analog scale (range, 1-10). Statistical analysis was performed by using the t test and χ2 test, with P < .05 considered indicative of a statistically significant difference. The full study protocol can be found at www.clinicaltrials.gov (NCT02270255). Results Participant demographic characteristics, fibroid volume, symptoms, and perceived sensitivity to pain were similar in both groups. Immediately after embolization, the pain score was lower in the SHNB group than in the sham group (mean, 1.0 ± 2.1 vs 2.6 ± 2.0, respectively; P = .01). The total need for fentanyl in the postanesthesia care unit was lower in the SHNB group than in the sham group (mean, 56 μg ± 67 vs 124 μg ± 91, respectively; P = .009). The morphine-equivalent dose needed was lower in the SHNB group than in the sham group (mean, 5.1 mg ± 5.8 vs 11.0 mg ± 9.0, respectively; P = .014). Of the 22 participants in the SHNB group, five (23%) needed antiemetics versus 12 of 22 participants (55%) in the sham group (P = .03). No difference in hospital admissions was observed between the two groups, and no major complications occurred from the SHNB. Conclusion Use of superior hypogastric nerve block reduces the amount of pain-related narcotics and antiemetics after uterine artery embolization. © RSNA, 2018.

PURPOSE:To assess frequency of adverse events, efficacy, and clinical outcomes of percutaneous portal vein embolization (PVE) in patients with bilobar colorectal liver metastases undergoing staged hepatectomy with preservation of segment IV ± I only. MATERIALS AND METHODS:Retrospective analysis was performed of 40 consecutive patients who underwent right PVE after successful left lobectomy between 2005 and 2013. Rates of adverse events, future liver remnant (FLR) > 30% compared with baseline liver volume, clinical success (completion of staged hepatectomy with clearance of liver metastases), and overall survival were analyzed. RESULTS:PVE was performed using polyvinyl alcohol particles (n = 7; 17.5%), particles plus coils (n = 23; 57.5%), and N-butyl cyanoacrylate glue plus ethiodized oil (n = 10; 25%). Technical success was 100%. After PVE, 20% (n = 8) of patients exhibited portal venous thrombosis, ranging from isolated intrahepatic portal branch thrombosis to massive thrombosis of the main portal vein (n = 3) and responsible for periportal cavernoma and portal hypertension in 5 patients. Of patients, 23 (57.5%) had FLR ≥ 30%, and 21 (52.5%) had clinical success. Six patients had significant stenosis or occlusion of the left portal vein or biliary system after original left lobectomy, which was independently associated with FLR < 30% (R2 = 0.24). Clinical success was the only independent variable associated with survival (R2 = 0.25). CONCLUSIONS:PVE for staged hepatectomy with preservation of segment IV ± I only is technically feasible, leading to adequate hypertrophy and clinical success rates in these patients with poor oncologic prognosis. Portal venous thrombosis is greater after the procedure than in the setting of standard PVE.

Purpose: Gastrojejunostomy tubes (GJTs) enable enteral nutrition in infants/ children with feeding intolerance. However, complicationsmay be increased in small infants. We evaluated our single-institution GJT complication rate and systematically reviewed existing literature.Methods: With REB approval, a retrospective single-institution analysis of GJT placements between 2009 and 2015 was performed. For the systematic review, MOOSE guidelines were followed.Results: At our institution, 48 children underwent 154/159 successful insertions primarily for gastroesophageal reflux (n - 27; 55%) and aspiration (n - 11; 23%). Median age at first GJT insertion was 2.2 years (0.2-18). Thirty-five (73%) had an index insertion when <= 10 kg. GJTs caused 2 perforations and 1 death. The systematic review assessed 48 articles representing 2726 procedures. Overall perforation rate was estimated as 2.1% (n = 36 studies, 23/1092, 95% CI: 1.0-3.2). Perforation rates in children <10 kg versus = 10 kg were estimated as 3.1%/ procedure (95% CI: 1.1%-5.0%) and 0.1%/ procedure (95% CI: 0%-0.3%), respectively. The relative risk of perforation was 9.4 (95% CI: 2.8-31.3). Overall mortality was estimated as 0.9%/ patient (n = 39 studies; 95% CI: 0.2-1.6%). Most perforations (19/23; 83%) occurred = 30 days of attempted tube placement.Conclusion: Gastrojejunostomy tubes are associated with significant complications and frequently require revision/replacement. Insertion in patients <10 kg is associated with increased perforation risk. Caution is warranted in this subgroup. (C) 2017 Elsevier Inc. All rights reserved.

This study is to assess whether a temporary nerve block performed immediately prior to thermal ablation for treatment of hepatic tumors reduces the need for IV medication induced conscious sedation during the ablation. Retrospective study performed between September 2015 and July 2016 during which some patients had received a celiac plexus or hepatic hilar nerve block for periprocedural pain control and others did not, based on operator ease and experience at performing the blocks. All patients having had ablation performed under conscious sedation rather than general anesthesia were included. Use of IV sedation during the procedure is provided by nursing staff following a standard protocol which includes 1 mg midazolam and 50 mcg fentanyl prior to starting the procedure. Exclusion criteria were patients in which IV sedation use was not recorded adequately or was not available. Nerve blocks were performed by the IR just before the thermal ablation. The control group of patients was those that did not receive a block. Consumption of fentanyl and midazolam recorded during the procedure were compared between both groups. 23 patients fit the inclusion and exclusion criteria. 10 did not receive any nerve block and 13 received a nerve block: 7 patients had a celiac plexus block and 6 patients had a hepatic hilum plexus block. Similar average tumor characteristics, Ablation time, and distance from tumor to capsule between groups. The average consumption for midazolam was 1.68 mg ( ± 0,59 SD) in patients who receive a nerve block and 2.55 mg ( ± 0,8 SD) in patients who did not (p = 0.013). The consumption of fentanyl in patients who received a nerve block was 123 μg ( ± 52 SD) and 195 μg ( ± 88 SD) in those who did not (p = 0.035). Only one of the patients who received a block had a self resolving bradycardia with no clinical implication. No major complications occurred in the nerve block group. Within the limits of a retrospective study, data demonstrates that hepatic hilum or celiac plexus blocks are safe and feasible tools to reduce use of IV sedation needed during liver thermal ablation. A prospective study would be needed to confirm this.

Understand the technique of superior hypogastric nerve block (SHNB) in uterine fibroid embolisation (UFE), its advantages and potential complications. Compare SHNB with other pain relief methods. UFE is commonly associated with severe pelvic pain that may require hospitalization for pain control, often with IV opioid analgesia. The pain typically begins during or soon after UFE, lasting for 8-12 hours, after which the pain reduces significantly. The superior hypogastric nerve plexus supplies uterine sensory innervation. It runs in the pre-vertebral space along S1 to L4 before crossing behind the aortic bifurcation superiorly. SHNB is performed via an anterior abdominal approach under fluoroscopic guidance. The catheter over the aortic bifurcation is used as a landmark after embolising the left uterine artery. A small gauge needle is advanced percutaneously to the centre of L5 below the aortic bifurcation. Contrast injection confirms needle tip in retroperitoneum. Regional block is performed by injecting long acting local anaesthetic. Intravascular anesthetic injection may lead to cardiac dysrhythmia and convulsions, easily avoided by test injection of contrast under fluoroscopy. Bacteremia from needle transgression of bowel is very rare. Injection of contrast into the vertebral disk can occur with no clinical significance. SHNB can eliminate the need for IV and epidural methods of pain control in UFE. It is safe and well tolerated; however, it adds approximately 10 minutes to overall UFE procedure time. SHNB makes the recovery period more comfortable for the patient and allows for same day discharge making UFE more cost-effective and accessible. Complications are rare.