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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.

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.

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.

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 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.

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.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.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).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.

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.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.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.Ultrasound elastography was able to diagnose cirrhosis, distinguish healthy from fibrotic liver tissue, and showed consistent liver stiffness values in children without liver disease.

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.

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.

PURPOSE: The aim of this study was to show the number of cases in which the use of fusion-guided ultrasonography (US) provided conclusive diagnosis of lesions in the liver seen on CT or MRI or PET/CT. A lesion is defined as a region that has suffered damage due to injury or disease. MATERIALS AND METHODS: Forty patients of whom 34 had confirmed neoplastic disease, referred to US evaluation or US-guided biopsy of liver lesions seen on CT (n = 35), MRI (n = 2) or PET/CT (n = 3), were prospectively included in the study. We used a LOGIQ prototype system with incorporated software for fusion imaging, and a convex-array 4 MHz transducer (GE Healthcare, Chalfont St. Giles, UK). All patients were initially examined with B-mode US, then by fusion-guided US and for some patients also with CEUS. All patients received follow-up after at least one year. RESULTS: Twenty-six lesions were initially indistinguishable with US. Of these, 9 became visible with fusion-guided US and another 4 became visible with CEUS, which facilitated a final diagnosis in 11 of these 13 patients. The median tumor size for all lesions included in the study was 1.5 cm (interquartile range: 1.0 - 2.4). There was no statistically significant difference in tumor size between the groups. CONCLUSION: We have successfully demonstrated an increase in the characterization of liver lesions by using fusion-guided US compared with conventional B-mode US.

Mesenteric blood flow is believed to be influenced by digestion and absorption of ingested macronutrients. We hypothesized that the intestinotrophic hormone, GLP-2 (glucagons-like peptide 2), may be involved in the regulation of mesenteric blood flow. Changes in mesenteric blood flow were measured by Doppler ultrasound scanning of the superior mesenteric artery (SMA). The aim of the study was to demonstrate the influence of GLP-2 on this flow, expressed as changes in resistance index (RI).A homogeneous group of 10 fasting healthy volunteers completed a 2-day trial. On day 1, a standard meal was given, and RI measured in the SMA. On day 2, GLP-2 was infused intravenously (IV) at rates of 0.5, 1.0 and 2.0 pmol/kg/min over 3 x 45 min separated by a 15-20 min rest period. After a further 15-20 min of rest, 450 nmol synthetic GLP-2 was given subcutaneously (SC). RI in the SMA was measured before, during and after the meal and GLP-2 infusions.After IV infusion of GLP-2, the following decreases in RI were observed: 0.5 pmol/kg/min: 2.7% (range 0-6.3%), 1.0 pmol/kg/min: 6.7% (range 0.4-15.9%), 2.0 pmol/kg/min: 15.3% (range 9.6-22.7%) p0.00802. When given SC, GLP-2 elicited a maximum average change in RI of 15.6% (range 5.0-28.1%). The standard meal elicited a 14.7% (range 8.8-21.6%) change, p0.020 There was a similar change in RI over time (0-90 min) after a standard meal and after subcutaneous GLP-2, p0.005.Our study showed a significant association between IV and SC administration of synthetic GLP-2 and changes in mesenteric blood flow. An exponential dose-response relationship was observed after IV infusion. The meal-induced changes in mesenteric blood flow over time were similar to those obtained by SC GLP-2. Thus, our results support the hypothesis that GLP-2 is an important regulator of mesenteric blood flow.

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.

Purpose: To investigate the intra- and inter-tester reproducibility of measurements of the Achilles tendon, tibialis anterior tendon, and the tibialis posterior tendon in football players using ultrasound (US) and magnetic resonance imaging (MRI). Material and Methods: Eleven asymptomatic football players were examined. Using a standardized US scanning protocol, the tendons were examined by two observers with US for thickness, width, and cross-sectional area. One observer conducted the procedure twice. The subjects also underwent an MRI examination, and the assessment of tendon size was conducted twice by two observers. Results: The best reproducibility judged by coefficient of variation (CV) and 95% confidence interval was determined for the Achilles tendon on both US and MRI. The variability of US on measurements on the tibialis anterior and tibialis posterior tendons was less than that when using MRI. In 12 out of 18 measurements, there were systematic differences between observers as judged by one-sided F-test. Conclusion: The reproducibility of the three tendons was limited. Precaution should be taken when looking for minor quantitative changes, i.e., training-induced hypertrophy, and when doing so, the Achilles tendon should be used.

To explore the reliability and validity of the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale for point-of-care ultrasonography (POC US) performance.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.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.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; P0.001).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.

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.

Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. Trial registration number: NCT00781924.

A consecutive series of 89 patients (95 limbs) with gangrene were operated on with amputation of toes or some distal part of the foot after arterial reconstruction. 43 patients had diabetes. Healing was achieved in 81/82 feet when the reconstruction was open. Amputation below or above the knee was required in 4/5 limbs when the reconstruction failed. 8 patients died before healing. The median time to healing was 30 (17-452) days, after a single amputation, and 115 (36-466) days, when more than one procedure had been necessary. We concluded that amputations on the feet for gangrene usually heal after arterial reconstruction, in patients with diabetes as well as in those with arteriosclerosis. No weight bearing and control of infection are important during the early postoperative period.

Vaginal rupture is a rare complication of hysterectomy. It is, among others, related to age and the incidence is higher in postmenopausal women. The rupture can occur spontaneously or in relation to clinical follow-up. In ovarian cancer the follow-up after surgery includes clinical examination, cancer antigen (CA)-125, and transabdominal and transvaginal ultrasonography. We experienced vaginal rupture in three patients with ovarian cancer. All patients had undergone surgery for ovarian cancer and were receiving chemotherapy. The rupture occurred shortly after transvaginal ultrasonography, performed by separate radiologists specialised in ultrasonography. All patients had acute surgery without any complications. Caution should be taken when performing transvaginal ultrasonography in hysterectomised patients and the complication of vaginal rupture should always be borne in mind.