The impact of ultrasound on testicular loss in cases of testicular torsion in children.

PURPOSE: Ultrasound as a diagnostic tool in suspicion of testicular torsion is still highly debated. In this investigation, we aimed to evaluate whether time spent on scrotal ultrasonography had a negative impact on testicular loss. METHODS: Patients' records containing a scrotal ultrasound and/or surgical procedure codes for testicular interventions on suspicion of testicular torsion were examined. Patients aged 0-15 years admitted during 2015-2019 at Copenhagen University Hospital, Rigshospitalet were included. RESULTS: In total, 1566 patients underwent an ultrasound and 142 of these proceeded to surgery while 13 patients proceeded directly to surgery without an ultrasound. The rate of testicular loss with a preceding ultrasound was 23% versus 42% without (p = 0.18). Four cases of testicular torsion were misdiagnosed by ultrasound resulting in a sensitivity of 95.4% and specificity of 95.6%. The mean diagnostic delay from ultrasound examination was 55 ± 39 min, and the mean time from ultrasound to surgery was at 169 ± 76 min versus 171 ± 72 min without ultrasound. CONCLUSION: In a clinical setting, ultrasound provided a reliable tool for the diagnosis of testicular torsion and did not seem to increase the orchiectomy rate.

Noninvasive Prediction of Advanced Fibrosis in Pediatric Liver Disease-Discriminatory Performance of 2D Shear Wave Elastography, Transient Elastography and Magnetic Resonance Elastography in Comparison to Histopathology.

Background: Elastography can be measured with different imaging techniques and is increasingly used for noninvasive assessment of hepatic fibrosis. Little is known about the performance, and interrelation of different elastographic techniques, in prediction of hepatic fibrosis in pediatric liver disease. Objectives: We aimed to determine the discriminatory value for advanced fibrosis (Metavir F3-4) and evaluate the applicability of 2D shear wave ultrasound elastography (USe), Transient Elastography (TE) and Magnetic Resonance elastography (MRe) in pediatric liver disease. Methods: In patients with pediatric liver disease aged 0−19 years, USe, TE and MRe were compared with histopathological fibrosis stage. Multivariate logistic regression models for advanced fibrosis were considered. Discriminative performance was assessed by the area under the receiver operating characteristic curve and the Brier Score. Primary analyses included complete cases. Multiple imputation was used as sensitivity analysis. Results: In 93 histologically evaluated patients USe, TE and MRe were performed 89, 93 and 61 times respectively. With increased liver stiffness values, significantly increased odds for presenting F3-4 were seen in individual models for ALT < 470 U/L, whereas the effect for ALT > 470 U/L was non-significant. Area under the curve and Brier Score for discrimination of advanced fibrosis were 0.798 (0.661−0.935) and 0.115 (0.064−0.166); 0.862 (0.758−0.966) and 0.118 (0.065−0.171); 0.896 (0.798−0.994) and 0.098 (0.049−0.148) for USe, TE and MRe respectively. No significant increase in discriminatory ability was found when combining elastographic modalities. Conclusions: In pediatric liver disease, USe, TE and MRe had a good discriminatory ability for assessment of advanced liver fibrosis, although TE and MRe performed best. In most children with pediatric liver disease, TE is a reliable and easily applicable measure.

Lower urinary tract obstruction caused by fibroepithelial polyp in a newborn boy.

In this rare case we report a 3-week-old boy with postnatal continues stomach pains, crying and severe dysuria, caused by bladder outlet obstruction due to a histopathological confirmed fibroepithelial polyp in the prostatic urethra. The condition was diagnosed and fully treated with ultrasound and a therapeutic cystoscopy.

Ensuring competence in ultrasound-guided procedures-a validity study of a newly developed assessment tool.

OBJECTIVES: To investigate the validity of the Interventional Ultrasound Skills Evaluation (IUSE) tool for assessment of procedural competence in ultrasound-guided procedures in a clinical environment, including a pass/fail score. METHODS: Novices and experienced radiologists were recruited from four hospitals and were observed and assessed while performing ultrasound-guided procedures. Performances were assessed using the IUSE tool by two independent raters. Validity evidence was gathered in accordance with Messick's framework: response process was ensured by standardisation of written rater instructions. Internal structure was explored using Cronbach's alpha for internal consistency reliability; inter-rater reliability was calculated as Pearson's r independently across all ratings, and test-retest reliability was reported using Cronbach's alpha. Relationship to other variables was investigated by comparing performances of the participants in each group. Consequences evidence was explored by calculating a pass/fail standard using the contrasting groups method. RESULTS: Six novices and twelve experienced radiologists were enrolled. The IUSE tool had high internal consistency (Cronbach's alpha = 0.96, high inter-rater reliability (Pearson's r = 0.95), and high test-retest reliability (Cronbach's alpha = 0.98), and the mean score was 33.28 for novices and 59.25 for experienced with a highly significant difference (p value < 0.001). The pass/fail score was set at 55 resulting in no false positives or false negatives. CONCLUSIONS: Validity evidence from multiple sources supports the use of the IUSE tool for assessment of competence in ultrasound-guided procedures in a clinical environment and its use in high-stakes assessment such as certification. A credible pass/fail criterion was established to inform decision-making. KEY POINTS: • A multi-site validity investigation established that the Interventional Ultrasound Skills Evaluation (IUSE) tool can be used to assess procedural competence in ultrasound-guided procedures. • Validity evidence was gathered according to Messick's framework validity from the following sources: response process, internal structure, relationship to other variables, and consequences evidence. • The IUSE tool can be used for both formative and summative assessment, and a credible pass/fail score was established to help inform decision-making such as certification.

Liver fibrosis in patients with tetralogy of Fallot, an unrecognised complication?

OBJECTIVES: Improved survival has led to a growing population of adults with congenital heart disease (CHD), followed by numerous reports of late complications. Liver disease is a known complication in some patients, with most studies focusing on Fontan associated liver disease. Whether liver disease also exists in other patients with CHD is not fully investigated. Elevated central venous pressure is considered pivotal in the development of liver disease in Fontan associated liver disease, and other patients with alterations in central venous pressure may also be at risk for developing liver fibrosis. We wanted to see if liver fibrosis is present in patients with tetralogy of Fallot. Many patients with tetralogy of Fallot have severe pulmonary regurgitation, which can lead to elevated central venous pressure. Patients with tetralogy of Fallot may be at risk of developing liver fibrosis. MATERIALS AND METHODS: Ten patients (24-56 years) with tetralogy of Fallot and pulmonary regurgitation were investigated for liver fibrosis. All patients were examined with magnetic resonance elastography of liver, hepatobiliary iminodiacetic acid scan, indocyanine green elimination by pulse spectrophotometry, elastography via FibroScan, abdominal ultrasound including liver elastography, and blood samples including liver markers. RESULTS: Three out of ten patients had findings indicating possible liver fibrosis. Two of these had a liver biopsy performed, which revealed fibrosis stage 1 and 2, respectively. The same three patients had an estimated elevated central venous pressure in previous echocardiograms. CONCLUSIONS: Mild liver fibrosis was present in selected patients with tetralogy of Fallot and may be related to elevated central venous pressure.

Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.

Purpose: Pediatric cancers are often difficult to classify and can be complex to treat. To ensure precise diagnostics and identify relevant treatment targets, we implemented comprehensive molecular profiling of consecutive pediatric patients with cancer relapse. We evaluated the clinical impact of extensive molecular profiling by assessing the frequency of identified biological onco-drivers, altered diagnosis, and/or identification of new relevant targeted therapies. Patients and Methods: Forty-six tumor samples (44 fresh-frozen; two formalin-fixed paraffin embedded), two bone marrow aspirates, three cerebrospinal fluid samples, and one archived DNA were obtained from 48 children (0-17 years; median 9.5) with relapsed or refractory cancer, where the disease was rapidly progressing in spite of their current treatment or they had exhausted all treatment options. The samples were analyzed by whole-exome sequencing (WES), RNA sequencing (RNAseq), transcriptome arrays, and SNP arrays. Final reports were available within 3-4 weeks after patient inclusion and included mutation status, a description of copy number alterations, differentially expressed genes, and gene fusions, as well as suggestions for targeted treatment. Results: Of the 48 patients, 33 had actionable findings. The most efficient method for the identification of actionable findings was WES (39%), followed by SNP array (37%). Of note, gene fusions were identified by RNAseq in 21% of the samples. Eleven findings led to clinical intervention, i.e., oncogenetic counseling, targeted treatment, and treatment based on changed diagnosis. Four patients received compassionate use targeted therapy. Six patients experienced direct benefits in the form of stable disease or response. Conclusion: The application of comprehensive genetic diagnostics in children with recurrent cancers allowed for discovery and implementation of effective targeted therapies and hereby improvement of outcome in some patients.

Effect of Liraglutide Treatment on Jejunostomy Output in Patients With Short Bowel Syndrome: An Open-Label Pilot Study.

BACKGROUND: An impaired hormonal "ileo-colonic brake" may contribute to rapid gastric emptying, gastric hypersecretion, high ostomy losses, and the need for parenteral support in end-jejunostomy short bowel syndrome (SBS) patients with intestinal failure (IF). Liraglutide, a glucagon-like peptide 1 receptor agonist, may reduce gastric hypersecretion and dampen gastric emptying, thereby improving conditions for intestinal absorption. MATERIALS AND METHODS: In an 8-week, open-label pilot study, liraglutide was given subcutaneously once daily to 8 end-jejunostomy patients, aged 63.4 ± 10.9 years (mean ± SD) and with small bowel lengths of 110 ± 66 cm. The 72-hour metabolic balance studies were performed before and at the end of treatment. Food intake was unrestricted. Oral fluid intake and parenteral support volume were kept constant. The primary end point was change in the ostomy wet weight output. RESULTS: Liraglutide reduced ostomy wet weight output by 474 ± 563 g/d from 3249 ± 1352 to 2775 ± 1187 g/d (P = .049, Student t test). Intestinal wet weight absorption tended to increase by 464 ± 557 g/d (P = .05), as did urine production by 765 ± 759 g/d (P = .02). Intestinal energy absorption improved by 902 ± 882 kJ/d (P = .02). CONCLUSION: Liraglutide reduced ostomy wet weight output in end-jejunostomy patients with SBS-IF and increased their intestinal wet weight and energy absorption. If larger, randomized, placebo-controlled studies confirm these effects, it adds to the hypothesis that many ileo-colonic brake hormones in conjunction may be involved in the process of intestinal adaptation. By identification of key hormones and addressing their potential synergistic effects, better treatments may be provided to patients with SBS-IF. This trial was registered at clinicaltrialsregister.eu as 2013-005499-16.

Competency-based assessment in surgeon-performed head and neck ultrasonography: A validity study.

OBJECTIVE: Head and neck ultrasonography (HNUS) increasingly is used as a point-of-care diagnostic tool by otolaryngologists. However, ultrasonography (US) is a very operator-dependent image modality. Hence, this study aimed to explore the diagnostic accuracy of surgeon-performed HNUS and to establish validity evidence for an objective structured assessment of ultrasound skills (OSAUS) used for competency-based assessment. STUDY DESIGN: A prospective experimental study. METHODS: Six otolaryngologists and 11 US novices were included in a standardized test setup for which they had to perform focused HNUS of eight patients suspected for different head and neck lesions. Their diagnostic accuracy was calculated based on the US reports, and two blinded raters assessed the video-recorded US performance using the OSAUS scale. RESULTS: The otolaryngologists obtained a high diagnostic accuracy on 88% (range 63%-100%) compared to the US novices on 38% (range 0-63%); P < 0.001. The OSAUS score demonstrated good inter-case reliability (0.85) and inter-rater reliability (0.76), and significant discrimination between otolaryngologist and US novices; P < 0.001. A strong correlation between the OSAUS score and the diagnostic accuracy was found (Spearman's ρ, 0.85; P < P 0.001), and a pass/fail score was established at 2.8. CONCLUSION: Strong validity evidence supported the use of the OSAUS scale to assess HNUS competence with good reliability, significant discrimination between US competence levels, and a strong correlation of assessment score to diagnostic accuracy. An OSAUS pass/fail score was established and could be used for competence-based assessment in surgeon-performed HNUS. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1346-1352, 2018.

Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy.

Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured. Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy and the evaluation CT scan, leaving twelve patients for analysis. Early changes in perfusion parameters using DCE-US did not correlate well with subsequent CT changes. A subgroup analysis of eight patients receiving bevacizumab, however, demonstrated a statistically significant correlation (p = 0.045) between early changes in perfusion measures of peak enhancement at DCE-US and tumor shrinkage at CT scan. The study indicates that early changes in DCE-US perfusion measures may predict subsequent treatment response of colorectal liver metastases in patients receiving bevacizumab.

Ultrasound Elastography Is Useful for Evaluation of Liver Fibrosis in Children-A Systematic Review.

OBJECTIVES: Adult studies have proven ultrasound elastography as a validated measure of liver fibrosis. The present study aimed to review the available literature on ultrasound elastography in children to evaluate the ability of the method to distinguish healthy from fibrotic liver tissue and investigate whether cutoff values for liver fibrosis in children have been established. METHODS: A literature search was performed in MEDLINE, EMBASE, the Cochrane Library, and Web of Science to identify studies on ultrasound elastography of the liver in children. Only original research articles in English concerning ultrasound elastography in children with and without liver disease, younger than 18 years, were included. All reference lists of the included articles were hand-searched for further references. RESULTS: Twenty-seven articles were included. Elastography in children without liver disease was investigated in 14 studies and were comparable to those existing for adults. Twelve studies compared elastography with liver biopsy in children with liver disease and found that cirrhosis was correctly diagnosed, whereas it was more difficult to assess severe fibrosis correctly. For the distinction between no, mild, and moderate fibrosis in children with liver disease the method was less accurate. Ultrasound elastography was able to differentiate between children with and without liver fibrosis. In children without liver disease ultrasound, elastography showed consistent liver stiffness values comparable to those found in adults. No fibrosis-specific cutoffs were proposed. CONCLUSIONS: Ultrasound elastography was able to diagnose cirrhosis, distinguish healthy from fibrotic liver tissue, and showed consistent liver stiffness values in children without liver disease.

Transfer from point-of-care Ultrasonography training to diagnostic performance on patients--a randomized controlled trial.

BACKGROUND: Clinicians are increasingly using point-of-care ultrasonography for bedside examinations of patients. However, proper training is needed in this technique, and it is unknown whether the skills learned from focused Ultrasonography courses are being transferred to diagnostic performance on patients. METHODS: Thirty-one physicians were randomized to participate in a focused Ultrasonography course or control circumstances before they examined 4 patients with different abdominal conditions by ultrasonography. Performance scores and diagnostic accuracy were compared using independent samples t test and binary logistic regression, respectively. RESULTS: There was a significant difference in the performance score between the intervention group (27.4%) and the control group (18.0%, P = .004) and the diagnostic accuracy between the intervention group (65%) and the control group (39%, P = .014). CONCLUSIONS: Clinicians could successfully transfer learning from an Ultrasonography course to improve diagnostic performance on patients. However, our results also indicate a need for more training when new technologies such as point-of-care ultrasonography are introduced.

Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L-asparaginase. We tested whether serial ultrasound examinations could predict asparaginase-associated pancreatitis (AAP). METHODS: Children (aged 1.0-17.9 years) with childhood ALL treated at the University Hospital Rigshopitalet, Copenhagen, according to the standard or intermediate risk arms of the NOPHO ALL2008 protocol, with PEG-asparaginase of 2 or 6 week intervals, for 30 weeks had their pancreas monitored using serial ultrasound in order to detect early signs of inflammation. RESULTS: Nineteen of 31 eligible patients were included. Three of the included patients developed AAP. None of the patients, including the three patients that developed AAP, had signs of inflammatory edema or pancreas enzymes above three times the upper normal limit prior to AAP. CONCLUSION: We found no signs of inflammatory edema within the pancreas on ultrasound during treatment with PEG-asparginase in our cohort prior to development of AAP or in patients that did not develop AAP.

Reliable and valid assessment of point-of-care ultrasonography.

OBJECTIVE: To explore the reliability and validity of the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale for point-of-care ultrasonography (POC US) performance. BACKGROUND: POC US is increasingly used by clinicians and is an essential part of the management of acute surgical conditions. However, the quality of performance is highly operator-dependent. Therefore, reliable and valid assessment of trainees' ultrasonography competence is needed to ensure patient safety. METHODS: Twenty-four physicians, representing novices, intermediates, and experts in POC US, scanned 4 different surgical patient cases in a controlled set-up. All ultrasound examinations were video-recorded and assessed by 2 blinded radiologists using OSAUS. Reliability was examined using generalizability theory. Construct validity was examined by comparing performance scores between the groups and by correlating physicians' OSAUS scores with diagnostic accuracy. RESULTS: The generalizability coefficient was high (0.81) and a D-study demonstrated that 1 assessor and 5 cases would result in similar reliability. The construct validity of the OSAUS scale was supported by a significant difference in the mean scores between the novice group (17.0; SD 8.4) and the intermediate group (30.0; SD 10.1), P = 0.007, as well as between the intermediate group and the expert group (72.9; SD 4.4), P = 0.04, and by a high correlation between OSAUS scores and diagnostic accuracy (Spearman ρ correlation coefficient = 0.76; P < 0.001). CONCLUSIONS: This study demonstrates high reliability as well as evidence of construct validity of the OSAUS scale for assessment of POC US competence. Hence, the OSAUS scale may be suitable for both in-training as well as end-of-training assessment.

[Management of patients with liver traumas].

Development of a hepatic pseudoaneurysm (HPA) is a well-known, yet rare complication after liver trauma. We found 135 cases reported in the literature since 1965. Ruptured HPAs may have severe consequences with sudden massive haemorrhage and death. A clear strategy towards diagnosis and management of HPA post liver trauma is needed and outlined in this paper. We recommend early detection and definitive treatment before enlargement and rupture.

Staging of cervical lymph nodes in oral squamous cell carcinoma: adding ultrasound in clinically lymph node negative patients may improve diagnostic work-up.

INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US) is a non-expensive, accessible and non-ionising imaging modality this method is not consistently used. This study aimed to investigate if addition of US of patients classified as clinically LN negative (cN0) by CT and/or MRI, increases the detection of LN metastases. Also, we aimed to identify which of the sonographic characteristics: echogenicity, border, shape, appearance of hilum and nodal blood-flow pattern best detect metastases in this patient group. METHOD: Fifty-one patients with OSCC classified as cN0 by CT/MRI were consecutively included and prospectively examined with US prior to sentinel node biopsy or selective neck dissection. Localisation, size and sonographic characteristics were registered for each LN and compared with the pathological findings. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different size measurements and sonographic characteristics. RESULTS: We found that short axial diameter was the best size criterion for detection of metastases. However, the sonographic characteristics were better predictors than size and the presence at least four of the sonographic characteristics: hypo-echoic or heterogeneous appearance; irregular border; spherical shape; absence of nodal hilum; and peripheral nodal blood-flow resulted in a sensitivity of 43.8; specificity 91.4; PPV 70.0; and NPV 78.0. The number of patients with occult metastases decreased from 16 out of 51 (31%) to nine out of 51 (18%). Three patients (6%) were over-staged by US. CONCLUSION: The addition of US to the clinical work-up of patients with cN0 OSCC increases the detection of metastases, thus US potentially reduces the number of patients requiring a secondary neck surgery after sentinel node biopsy.

[Acute, severe liver insufficiency caused by extrahepatic biliary atresia in a newborn]. / Akut, svær leverinsufficiens forårsaget af binyretumor hos nyfødt.

A newborn female was hospitalized due to metabolic acidosis and conjugated hyperbilirubinaemia. Extrahepatic biliary atresia (EHBA) was suspected why a (99m)Tc-mebrofenin cholescintigraphy was performed. It showed poor hepatocyte tracer uptake and no drainage to the gut. The hepatocyte dysfunction was caused by an obstructing adrenal gland neuroblastoma later visualised by ultrasound and MRI. The cholescintigraphy is a non-invasive modality to exclude or confirm the suspicion of EHBA. Furthermore neonatal conjugated hyperbilirubinaemia demands the use of a multimodality imaging strategy for differential diagnosis to EHBA.

Positron emission tomography/computed tomography in the staging and treatment of anal cancer.

PURPOSE: This study was intended to determine the role of PET/CT in the staging of anal cancer as a supplement to three-dimensional transanal ultrasound (TAUS) and inguinal ultrasound (US). The impact of the PET/CT on the initial stage and treatment plan proposed by TAUS/US was assessed. METHODS AND MATERIALS: Ninety-five (95) patients referred to our clinic between July 1, 2005, and December 31, 2009, were retrospectively reviewed. All patients had biopsy-proven primary squamous cell cancer of the anal canal. There were 65 females (68%) and 30 males (32%), and the median age was 58 years (range, 35-88 years). Six (6%) of the patients were HIV positive. All patients were staged with TAUS/US and PET/CT. RESULTS: Twenty-eight (28) patients were diagnosed with suspicious perirectal node metastases. TAUS visualized 24 of these, whereas PET/CT detected 15. Suspicious inguinal nodes were visualized on either US or PET/CT in 41 patients. Seventeen (17) of these had confirmed malignant disease on biopsy, and 15 had confirmed benign disease. All 17 patients (100%) with malignant inguinal nodes were diagnosed by PET/CT, whereas US identified 16 (94%). Ten patients were diagnosed with suspicious inguinal nodes on PET/CT that had not been seen on US. One of these was malignant, three were benign, and six were not biopsied. PET/CT diagnosed eight metastatic sites, whereas TAUS/US diagnosed three. PET/CT discovered three of the five synchronous cancers seen in this study. PET/CT upstaged the disease in 14% of the cases and changed the treatment plan proposed by TAUS/US in 17%. CONCLUSION: PET/CT has great potential influence on the staging and treatment of anal cancer. TAUS is important in the staging of the primary tumor and N1-stage, whereas PET/CT seems necessary for the N2/3-stage, the M-stage and synchronous cancers.

Improving Accuracy for Image Fusion in Abdominal Ultrasonography.

Image fusion involving real-time ultrasound (US) is a technique where previously recorded computed tomography (CT) or magnetic resonance images (MRI) are reformatted in a projection to fit the real-time US images after an initial co-registration. The co-registration aligns the images by means of common planes or points. We evaluated the accuracy of the alignment when varying parameters as patient position, respiratory phase and distance from the co-registration points/planes. We performed a total of 80 co-registrations and obtained the highest accuracy when the respiratory phase for the co-registration procedure was the same as when the CT or MRI was obtained. Furthermore, choosing co-registration points/planes close to the area of interest also improved the accuracy. With all settings optimized a mean error of 3.2 mm was obtained. We conclude that image fusion involving real-time US is an accurate method for abdominal examinations and that the accuracy is influenced by various adjustable factors that should be kept in mind.