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Purpose: The purpose of this study was to evaluate the clinical benefits of nivolumab with/without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with pretreated metastatic biliary tract cancer (mBTC)., Patients and Methods: The study was a phase 2 randomized trial with Simon's optimal two-stage design requiring 36 evaluable patients per group after second stage. Sixty-one patients were included from September 2018 to January 2022 and randomized (1:1) to receive SBRT (15 Gy × 1 on day 1 to a primary or metastatic lesion) and nivolumab (3 mg/kg intravenously on day 1 and every 2 weeks) with/without ipilimumab (1 mg/kg intravenously on day 1 and every 6 weeks). Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients with complete response, partial response, or stable disease. Decision to continue accrual into the second stage depended on the CBR from the first stage., Results: Forty-two patients received SBRT/nivolumab/ipilimumab with a CBR of 31.0% [95% confidence interval (CI), 17.6-47.1]. Five patients (11.9%) achieved partial response with median duration of 4.4 months (range, 1.1-21.5). Nineteen patients received SBRT/nivolumab. This group was closed after the initial stage based on a CBR of 10.5% (95% CI, 1.3-33.1). Adverse events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Grade ≥3 treatment-related adverse events occurred in 13 (31%) and 3 (16%) patients in the SBRT/nivolumab/ipilimumab and SBRT/nivolumab groups, respectively. One patient died from immune-related hepatitis in the SBRT/nivolumab/ipilimumab group., Conclusions: Combining SBRT, nivolumab, and ipilimumab is well tolerated, feasible, and shows response in a subgroup of patients with mBTC., (©2024 American Association for Cancer Research.)

Background: Individual placement and support (IPS) is an evidence-based practice that helps individuals with mental illness gain and retain employment. IPS was implemented for young adults at a municipality level through a cross-sectoral collaboration between specialist mental healthcare, primary mental healthcare, and the government funded employment service (NAV). We investigated whether IPS implementation had a causal effect on employment outcomes for all young adults in receipt of a temporary health-related rehabilitation (work assessment allowance, WAA) welfare benefit, measured at the societal level compared to municipalities that did not implement IPS., Method: We used a difference in differences design to estimate the effects of IPS implementation on the outcome of workdays per year using longitudinal registry data. We estimate the average effect of being exposed to IPS implementation during four-years of implementation compared to ten control municipalities without IPS for all WAA recipients., Results: We found a significant, positive, causal effect on societal level employment outcomes of 5.6 ( p = 0.001, 95% CI 2.7-8.4) increased workdays per year per individual, equivalent to 12.7 years of increased work in the municipality where IPS was implemented compared to municipalities without IPS. Three years after initial exposure to IPS implementation individuals worked, on average, 10.5 more days per year equating to 23.8 years of increased work., Conclusions: Implementing IPS as a cross sectoral collaboration at a municipality level has a significant, positive, causal, societal impact on employment outcomes for all young adults in receipt of a temporary health-related rehabilitation welfare benefit.

Background: Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical study NCT03715985 showed that the personalized peptide-based neoantigen vaccine EVX-01, formulated in the liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific T cell responses in patients with metastatic melanoma. Here, we present results from the dose-escalation part of the study, evaluating the feasibility, safety, efficacy, and immunogenicity of EVX-01 in addition to anti-PD-1 therapy., Methods: Patients with metastatic melanoma on anti-PD-1 therapy were treated in three cohorts with increasing vaccine dosages (twofold and fourfold). Tumor-derived neoantigens were selected by the AI platform PIONEER and used in personalized therapeutic cancer peptide vaccines EVX-01. Vaccines were administered at 2-week intervals for a total of three intraperitoneal and three intramuscular injections. The study's primary endpoint was safety and tolerability. Additional endpoints were immunological responses, survival, and objective response rates., Results: Compared with the base dose level previously reported, no new vaccine-related serious adverse events were observed during dose escalation of EVX-01 in combination with an anti-PD-1 agent given according to local guidelines. Two patients at the third dose level (fourfold dose) developed grade 3 toxicity, most likely related to pembrolizumab. Overall, 8 out of the 12 patients had objective clinical responses (6 partial response (PR) and 2 CR), with all 4 patients at the highest dose level having a CR (1 CR, 3 PR). EVX-01 induced peptide-specific CD4+ and/or CD8+T cell responses in all treated patients, with CD4+T cells as the dominating responses. The magnitude of immune responses measured by IFN-γ ELISpot assay correlated with individual peptide doses. A significant correlation between the PIONEER quality score and induced T cell immunogenicity was detected, while better CRs correlated with both the number of immunogenic EVX-01 peptides and the PIONEER quality score., Conclusion: Immunization with EVX-01-CAF09b in addition to anti-PD-1 therapy was shown to be safe and well tolerated and elicit vaccine neoantigen-specific CD4+and CD8+ T cell responses at all dose levels. In addition, objective tumor responses were observed in 67% of patients. The results encourage further assessment of the antitumor efficacy of EVX-01 in combination with anti-PD-1 therapy., Competing Interests: Competing interests: MD has received honoraria for lectures from Roche and Novartis (past 2 years). IMS has received honoraria for lectures and consultancies from Novartis, Roche, MSD, BMS, and Pierre Fabre. KB has received honoraria (institutional) for lectures and advisory boards of MSD, Pierre Fabre, and BMS. CCIT-DK has been granted economic support for personal wages from Evaxion Biotech A/S, Denmark. SRH is a cofounder of PokeACell and coinventor of several licensed patents. ABS, DK-K, AJ, NVP, NT and JK are employees of Evaxion Biotech A/S and have a financial interest in the company. All other authors have declared that they have no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In this study we investigated the health-related rehabilitation trajectories of young Norwegian adults between 2004-2019. The study period is interesting because it overlaps with an extensive welfare system reform that occurred in Norway between 2006-2011. In parallel with the reform there was a substantial increase in health-related welfare dependency among young people due to mental health conditions. To better understand this group, we addressed three questions: 1) what were the most typical health-related rehabilitation trajectories for young Norwegians aged 23-27 between 2004-2019, 2) did the trajectories and composition of health-related benefit recipients change overtime and 3) in parallel with the welfare reform, do we see improved labour market outcomes in our study population?, Methods: Using high-quality Norwegian registry data, we established four cohorts of Norwegian health-related rehabilitation benefit recipients aged 23-27 in either 2004 (cohort 1), 2008 (cohort 2), 2011 (cohort 3) or 2014 (cohort 4). The follow-up period for each cohort was six years. We used sequence and cluster analyses to identify typical health-related rehabilitation trajectories. In addition, descriptive statistics and multinomial logistic regression were used to scrutinise the relationship between trajectory types, sociodemographic characteristics and cohort membership., Results: The majority follow trajectories consisting of welfare dependency, unemployment and unstable, low-income work. Both the trajectories and composition of the study population changed across cohorts. Over the observation period there was a 1) three-fold increase in the proportion following a trajectory ending in permanent disability benefits, 2) nine-fold increase in the proportion following trajectories characterised by long periods of health-related rehabilitation, 3) five-fold decrease in the share following unemployment occupational handicap trajectories 4) 6.9% increase in the proportion of early school leavers and 5) 8.9% decrease in the share with disabled parents., Conclusion: Our study population is a vulnerable group with suboptimal mental health, functioning and employment outcomes. In conjunction with the welfare reform, we witnessed a significant drop in use of work-related benefits, accompanied by a substantial increase in uptake of health-related rehabilitation- and disability benefits. Thus, it appears that rather than improving employment outcomes, welfare policy changes have created a new problem by steering a greater proportion into disability benefits., (© 2023. The Author(s).)

Purpose: Ablation is a valuable treatment alternative to surgery for colorectal liver metastases. This study reports the long-term clinical outcomes in patients treated with ablation for colorectal liver metastases with or without extrahepatic metastases., Methods: Patients with colorectal liver metastases treated with ultrasound-guided ablation at Herlev Hospital, Denmark were included in this retrospective study., Results: This study included 284 patients with 582 metastases. Complete ablation was obtained in 258 patients (91%) evaluated within 6 weeks. During follow-up, 94 patients (33%) developed local recurrence. The median survival for all patients was 31 months, with 1-, 3-, and 5-year survival rates of 82%, 45%, and 21%, respectively. The median survival for patients with extrahepatic metastases (n=49, 17%) was 24 months compared with 33 months for patients without (P=0.142). Propensity score-adjusted Cox regression showed that extrahepatic metastases were associated with increased mortality, with a hazard ratio (HR) of 1.45 (95% confidence interval [CI], 1.02 to 2.05; P=0.039). In multivariate Cox regression analysis for all patients, increased mortality risk was found for a diameter ≥2.6 cm (HR, 1.59; 95% CI, 1.23 to 2.05), >1 metastasis (HR, 1.66; 95% CI, 1.28 to 2.16), and extrahepatic metastases (HR, 1.45; 95% CI, 1.04 to 2.03). Male sex (HR, 0.75; 95% CI, 0.58 to 0.98) and receiving chemotherapy (HR, 0.69; 95% CI, 0.52 to 0.92) were associated with decreased mortality., Conclusion: Ablation for colorectal liver metastases offers acceptable survival rates, including for patients with extrahepatic metastases. In addition, chemotherapy was associated with improved survival for both patients with and without extrahepatic metastases.

Background: Interleukin-6 blockade and radiation combined with immunotherapy may modulate the tumour microenvironment to overcome immune resistance. We assessed the efficacy of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy (SBRT) in patients with refractory pancreatic cancer (PC)., Methods: Patients with PC who had progressive disease (PD) or intolerance to gemcitabine- or fluorouracil-containing regimens were enrolled in Part A of the two-part, single-centre, phase 2 study (NCT04258150). SBRT with 15 Gy was administered on day one of the first cycle. Ipilimumab was administered (1 mg/kg every 6 weeks) for a maximum of two infusions. Nivolumab (6 mg/kg) and tocilizumab (8 mg/kg) were given every four weeks until the PD or unacceptable toxicity, or for up to one year. The primary end-point was the objective response rate, with a threshold of 15%., Results: Twenty-six patients were enrolled and treated between April 17, 2020, and January 25, 2021. The median follow-up time at the time of data cutoff (February 7, 2022) was 4.9 months (interquartile range 2.1-7.7). No responses were observed. Five patients (19%; 95% confidence intervals [CI], 7-39) achieved a stable disease. The median progression-free survival was 1.6 months (95% CI 1.4-1.7), and the median overall survival was 5.3 months (95% CI 2.3-8.0). Overall, 19 (73%) experienced adverse events related to the treatment including two (8%) with grade 3 or higher events., Conclusion: The combination of ipilimumab, nivolumab, tocilizumab, and SBRT in patients with PC did not meet the prespecified criteria for expansion for full accrual., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Immunotherapy with checkpoint inhibitors (CPIs) has revolutionised cancer treatment but has no convincing effect in metastatic castration-resistant prostate cancer (mCRPC). It has been suggested that a combination of CPI and hypofractionated stereotactic body radiotherapy (SBRT) may work synergistically, and recent trials have supported this. We hypothesise that adding SBRT to CPI treatment can improve response rates in patients with mCRPC., Methods and Analysis: The CheckPRO trial is an open-label, randomised, two-stage, phase II trial. We aim to enrol and randomise 80 evaluable patients with mCRPC who progressed following ≥2 lines of treatment. Enrolment started in November 2019 with 38 months expected enrolment period. The participants receive treatment for 52 weeks including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment.Co-primary endpoints are the objective response rate and prostate-specific antigen (PSA) response rate. Secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life and overall survival. Exploratory endpoints include translational analyses of tumour biopsies and consecutive blood samples. Biopsies from metastatic sites are collected at baseline, before the third treatment and at the end of treatment. Blood sampling for immune monitoring and circulating tumour DNA is performed consecutively at baseline and every radiographic assessment., Ethics and Dissemination: This study follows the Helsinki Declaration and is approved by the Danish Ethics Committee System (journal no. H-19016100). All participants must receive written and oral information and provide a signed informed consent document prior to inclusion. The study results will be published in an international peer-review journal., Trial Registration Number: EudraCT number: 2018-003461-34., Clinicaltrials: gov ID NCT05655715., Competing Interests: Competing interests: DLN, EVH, GA-F and ST have no conflict of interest. NJS has received conference participation from Pfizer Inc and a research grant from Herlev Hospital and Rigshospitalet, sponsored by Varian Medical Systems. Within the last two years IMS has received honoraria for consultancies and lectures from IO Biotech, Novartis, MSD, Pierre Fabre, BMS, Novo Nordisk, TILT Bio; research grants from IO Biotech, BMS, Lytix, Adaptimmune, TILT Bio. Within the last two years GFP has received conference participance from MSD, Daiichi Sankyo and Pfizer Pierre Fabre. Research grants from Varian Medical Systems and honoraria for consultancies and lectures from Astra Zeneca. RLE has received honoraria for consultancies and lectures from Amgen and received funding of study drugs from Bristol-Myers Squibb in the CheckPRO trial., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The World Federation of Ultrasound in Medicine and Biology (WFUMB) is addressing the issue of incidental findings with a series of position papers to give advice on characterization and management. The biliary system (gallbladder and biliary tree) is the third most frequent site for incidental findings. This first part of the position paper on incidental findings of the biliary system is related to general aspects, gallbladder polyps and other incidental findings of the gallbladder wall. Available evidence on prevalence, diagnostic work-up, malignancy risk, follow-up and treatment is summarized with a special focus on ultrasound techniques. Multiparametric ultrasound features of gallbladder polyps and other incidentally detected gallbladder wall pathologies are described, and their inclusion in assessment of malignancy risk and decision- making on further management is suggested., Competing Interests: Conflict of Interest disclosure The authors and participating institutions have no conflicts of interest related to this article. No funding was received to support data acquisition or preparation of this position paper. All fugures were provided by the authors, and data was acquired according to protocols approved by the institutional review boards of the authors. According to these protocols, participants gave consent for the use of their fully anonymized data (ultrasound images) in this article., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC)., Methods: Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status (ClinicalTrials.gov identifier: NCT02866383). The primary end point was the clinical benefit rate (CBR), defined as the percentage of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon's 2-stage phase II optimal design was used independently for both arms, with CBR determining expansion to the second stage. Secondary end points included safety, response rate, duration of response, progression-free survival, and overall survival. Exploratory analyses included biomarkers related to the benefits., Results: Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (8.0 to 30.6) for patients receiving SBRT/nivolumab and 37.2% (24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient receiving SBRT/nivolumab and lasted for 4.6 months. Six patients receiving SBRT/nivolumab/ipilimumab achieved a PR with a median duration of response of 5.4 months (4.2 to not reached). Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) and 13 (30.2%) patients in the SBRT/nivolumab and SBRT/nivolumab/ipilimumab groups, respectively. Programmed cell death ligand-1 expression by tumor proportion score or combined positivity score of ≥ 1% was not associated with clinical benefits. On-treatment decreased serum interleukin-6, interleukin-8, and C-reactive protein levels were associated with better overall survival., Conclusion: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory mPC. However, the contribution from SBRT is unknown. Further studies are warranted.

Background: Since the 1990's, structural transformations in the Norwegian economy have decreased employment opportunities for low-skilled young people lacking formal education credentials. In parallel with these economic changes, there has been a strong increase in the proportion of young disability pensioners. Preventing labour market exit requires a thorough understanding of the disability process. We aim to 1) identify the most typical trajectories into disability pension for young Norwegian inhabitants between 1993 and 2014 and 2) investigate if the trajectories and composition of young disability pensioners changed over time., Methods: Using high-quality Norwegian registry data, we established two population-based cohorts of Norwegian inhabitants aged 29-39 years in either 2003 (cohort 1) or 2014 (cohort 2) who were not disability pensioners during the first month of their cohort period but had been granted a disability pension by the cohort end-date. Cohort 1 was followed from the beginning of 1993 through 2003, cohort 2 from 2004 through 2014. We used sequence and cluster analyses to identify typical disability pension trajectories and investigate how they changed overtime., Results: The majority follow trajectories characterised by little or no previous work participation. Both the trajectories and composition of young disability pensioners changed overtime. Between the two cohorts there was 1) a doubling in the probability of following 'precarious income trajectories', 2) a decrease in the probability of following 'work and/or education trajectories' and 3) an increase in the proportion of early school leavers., Conclusion: Current initiatives such as the Norwegian Inclusive Workplace Agreement (IA) focus on preventing transitions from employment to disability benefits. However, such initiatives have little relevance for young disability pensioners as the majority have weak labour market attachment. Policymakers should therefore consider placing more emphasis on non-workplace interventions., Competing Interests: None., (© 2022 The Authors.)

Background: The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer., Methods: HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO 2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes., Discussion: To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy., Trial Registration: The study was prospectively registered at ClinicalTrials.gov on February 10 th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467., (© 2022. The Author(s).)

Background: The increased use of neoadjuvant chemotherapy (NACT) facilitates an increase in breast-conserving surgery and immediate breast reconstruction. While NACT is considered to have the same oncological safety as adjuvant chemotherapy, evidence on the impact of NACT on surgical outcomes following breast surgery is unclear and varies across studies. The aim of this systematic review and meta-analysis was to assess the impact of NACT on surgical complications in breast cancer patients undergoing any kind of breast surgery., Methods: Database searches were conducted (March 26, 2021) to identify studies assessing the impact of NACT on postoperative complications. Studies were included if they compared a group of patients treated with NACT to a control group that was not, and if they reported at least one of our defined outcomes. Primary effect measures were odds ratios (ORs) and mean difference with a 95% confidence interval. Study quality was assessed by the Newcastle-Ottawa Scale., Results: Twenty-six studies comprising 134,191 patients were included. NACT was not associated with an increased complication rate for overall complications (OR: 1.13, 95% CI: 0.86 to 1.47, p = 0.38), individual postoperative complications, nor surgery duration. There was a non-significant trend towards NACT increasing the risk of seroma, wound complications, skin or nipple necrosis, flap ischemia or loss, and implant loss. A significant difference in blood loss was found, favouring NACT (MD = -75.85, 95% CI: -107.47 to -44.23, p < 0.00001). Heterogeneity was significant between the studies (I 2 >50%)., Conclusion: Compared to a control group, NACT was not found to affect the surgical complications adversely., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis., Material and Methods: Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed., Results: A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% ( n  = 72) of the patients. A total of 31.3% ( n  = 25) of the patients received therapy either as targetable therapy outside an available trial ( n  = 2), FDA approved therapy ( n  = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% ( n  = 21)., Conclusion: Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.

Importance: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy., Objective: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs., Design, Setting, and Participants: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks., Main Outcomes and Measures: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity., Results: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups., Conclusions and Relevance: This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.

Neurofibromatosis type 1 (NF1) is a genetic disorder affecting the skin, nervous system, eyes and bones. Pulmonary involvement is unknown to many physicians. Yet, patients may be affected by lung bullae and cysts, which represent an increased risk for secondary spontaneous pneumothorax (SSP). We present a 56-year-old patient with a pathogenic variant of the NF1 gene, who suffered from NF1 with lung manifestations and recurrent SSP. It is essential to identify the patients having an increased risk of developing SSP as preventive surgery seem to decrease the risk of new events. Pneumothorax can be a clinical manifestation of NF1 but is not yet widely acknowledged as such., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This article represents part 3 of the EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound (GIUS). It provides an overview of the examination techniques recommended by experts in the field of endorectal/endoanal ultrasound (ERUS/EAUS), as well as perineal ultrasound (PNUS). The most important indications are rectal tumors and inflammatory diseases like fistula and abscesses in patients with or without inflammatory bowel disease (IBD). PNUS sometimes is more flexible and convenient compared to ERUS. However, the technique of ERUS is quite well established, especially for the staging of rectal cancer. EAUS also gained ground in the evaluation of perianal diseases like fistulas, abscesses and incontinence. For the staging of perirectal tumors, the use of PNUS in addition to conventional ERUS could be recommended. For the staging of anal carcinomas, PNUS can be a good option because of the higher resolution. Both ERUS and PNUS are considered excellent guidance methods for invasive interventions, such as the drainage of fluids or targeted biopsy of tissue lesions. For abscess detection and evaluation, contrast-enhanced ultrasound (CEUS) also helps in therapy planning.

US-guided percutaneous biopsy of focal liver lesions (FLL) is a classic interventional procedure performed by almost all radiology units. Typically, an incidental focal finding on US or a focal indeterminate lesion diagnosed on CT, MRI or PET/CT is referred for US-guided biopsy for final diagnosis. The introduction of microbubble US contrast agents has overcome some of the limitations of standard US in diagnosing FLLs by displaying the microvasculature together with the US morphology, which has increased both the sensitivity and the specificity. The combination of CEUS and intervention is facilitated by newer US equipment providing split-screen mode, which displays the CEUS mode alongside the standard US mode simultaneously on a single monitor. The puncture line is displayed in both modes as well as on the monitor. The interventional device (i. e., biopsy needle) is typically best visualized in the standard US mode, while the characteristic tissue pattern in an FLL is typically best visualized in CEUS mode. There are 3 main categories in which CEUS has an impact on US-guided biopsy of FLLs: • CEUS improves the visualization of FLLs • CEUS improves the quality of the biopsy specimen from an FLL • CEUS reduces the need for US-guided biopsy of an FLL In the two first categories, CEUS is utilized simultaneously with US-guided biopsy to ensure correct needle targeting. In the last category, US-guided biopsy of the FLL becomes superfluous as a result of the CEUS examination.

The aim of this article is to provide an inventory of the use of contrast-enhanced ultrasound (CEUS) in relation to percutaneous interventional procedures. The article is structured into a systematic literature review followed by a clinical part relating to percutaneous CEUS-guided procedures. A literature search identified 3109 records. After abstract screening, 55 articles were analyzed and supplemented with pictorial material to explain the techniques. In conclusion, the best-evidenced indications for CEUS-guided interventions are biopsy and ablation of inconspicuous or B-mode-invisible tumors, intraprocedural ablation control and follow-up, as well as percutaneous transhepatic cholangiography and drainage procedures., (© 2017 by the American Institute of Ultrasound in Medicine.)

Insufficient integration of immigrants into the labour market has been identified as a major problem in the Scandinavian countries Denmark, Norway and Sweden. Integration depends, inter alia, on immigration and integration policy, and for most of the post-war period the policies of the three countries displayed strong similarities. However, in the early 2000s Denmark increasingly deviated from its two neighbours, introducing more restrictive immigration and stricter integration policies. Comparing both pre- and post-reform immigrants across Scandinavia, we assess the wider impact of this comprehensive policy reversal by tracking the evolution of employment and earnings gaps between 1993 and 2006. We use large data sets with individual-level register information allowing us to account for immigrant labour force composition and to examine sub-groups of immigrants. The results do not indicate that the Danish reforms had any clear-cut effect on either employment or earnings among non-Western immigrants. Moreover, integration in Norway and Sweden was not unequivocally worse despite the absence of similar reforms, raising questions regarding the aptness of the Danish reversal., Competing Interests: Compliance with Ethical StandardsThere are no conflicts of interest.

Background and Aims: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development., Methods: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices., Results: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001)., Conclusions: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. All rights reserved.)

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Neoplasm seeding is a serious complication after liver metastases biopsy. Reported incidences vary between 10% and 19% for colorectal cancer (CRC) and are unknown for breast cancer (BC). The aim of this retrospective study was to determine the frequency of tumor seeding after ultrasound-guided percutaneous biopsy of CRC and BC liver metastases., Material and Methods: Unselected liver biopsies performed in the period of 2005-2012 at our institution were extracted from the National Pathology Registry. Medical records including imaging from patients with biopsy-verified BC and CRC liver metastases were retrospectively reviewed. The endpoint was the development of abdominal wall recurrence following liver biopsy., Results: Of total 2981 biopsies we identified 278 patients with CRC and 155 patients with BC biopsy-verified liver metastases. During the median follow-up of 25 months after biopsy (range 3-253 months), no seeding was recorded in patients with BC. Within the median follow-up of 34 months (3-111 months), seeding was registered in 17/278 (6%) of patients with CRC; three patients of 278 (1%) had undoubtedly biopsy-related seeding, which became apparent six, nine, and 26 months after biopsy, respectively; and in nine patients (3%) seeding occurred due to either biopsy or other interventions; and five patients had seeding, which were assessed as a consequence of other invasive procedures than biopsies. The median overall survival of the 17 patients with seeding was 70 months compared to 39 months of patients without seeding., Conclusions: The results showed no seeding in BC patients. Seeding rate after biopsy in CRC patients is not negligible, however, without affecting outcome.

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The intent of this review is to discuss and comment on common clinical scenarios in which contrast-enhanced ultrasonography (CEUS) may play a decisive role and to illustrate important points with typical cases. With the advent of CEUS, the scope of indications for ultrasonography has been dramatically extended, and now includes functional imaging and tissue characterization, which in many cases enable tumor diagnosis without a biopsy. It is virtually impossible to imagine the practice of modern medicine as we know it in high-income countries without the use of imaging, and yet, an estimated two thirds of the global population may receive no such care. Ultrasound imaging with CEUS has the potential to correct this inequity.

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound (INVUS) assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, and safe and effective performance of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

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

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

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (short version; the long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Hepatic metastases (HM) are amongst the most important prognostic factors in patient survival from colorectal cancer. The diagnostic imaging techniques for accurate detection and characterization of colorectal metastases are therefore vital. In a review of the literature, MRI showed the highest sensitivity for detection of HM lesions < 1 cm, but the amount of MR scanners is insufficient. Contrast-enhanced ultrasound and computed tomography have similar sensitivity for detection of HM, but each method also have limitation such as operator dependency or enhanced risk of cancer due to ionizing radiation.

Introduction: Most institutions perform percutaneous liver biopsy with a post-biopsy patient observation period lasting up to eight hours, which is resource-demanding. This study aimed to evaluate the safety of liver biopsy performed in a fast-track set-up with an only one-hour post-biopsy observation time., Methods: Patients referred to our institution underwent fast-track ultrasound-guided 18-gauge Tru-Cut liver biopsy procedures. Each single biopsy procedure was followed by a post-procedure observational period of one hour and an additional focused assessment with sonography for trauma before patient discharge. All patients underwent a clinical follow-up programme at revisit in order to register any delayed onset of major complications., Results: Out of 200 completed biopsy procedures, two major complications were registered post biopsy and they were treated appropriately. All patients were safely discharged from our institution. No fatality or long-term complications were found during this study., Conclusion: The fast-track approach reported herein is a feasible option when adequate patient information is given. Besides the obvious, positive effect on patient logistics and departmental throughput, this approach may also reduce diagnostic work-up time and bring financial benefits. Therefore, we encourage the use of this approach in institutions comparable to our own., Funding: not relevant., Trial Registration: not relevant.

Ectopic decidual reaction has been described in various intraperitoneal locations. We present a case of unusual ectopic decidual reaction in the groin mimicking inguinal lymphoma on ultrasound in a pregnant woman. This case contributes evidence illustrating the variability of the clinical presentation of ectopic decidual reaction.

Ultrasound (US) is an image modality providing the examiner with real-time images which reflect the morphological properties in soft tissue. Different types of transducers are used for different kind of exams. US is cheap, fast, and safe. US is widely used in abdominal imaging including obstetrics and gynaecology plus cardiology. Furthermore, US has gained significant interest in rheumatology, orthopaedics and anaesthetics. Colour Doppler and spectral Doppler is useful in vascular imaging. The use of US contrast increases accuracy in liver imaging. US can guide for different interventional procedures.

Background: Hospitals are merging to become more cost-effective. Mergers are often complex and difficult processes with variable outcomes. The aim of this study was to analyze the effect of mergers on long-term sickness absence among hospital employees., Methods: Long-term sickness absence was analyzed among hospital employees (N = 107 209) in 57 hospitals involved in 23 mergers in Norway between 2000 and 2009. Variation in long-term sickness absence was explained through a fixed effects multivariate regression analysis using panel data with years-since-merger as the independent variable., Results: We found a significant but modest effect of mergers on long-term sickness absence in the year of the merger, and in years 2, 3 and 4; analyzed by gender there was a significant effect for women, also for these years, but only in year 4 for men. However, men are less represented among the hospital workforce; this could explain the lack of significance., Conclusions: Mergers has a significant effect on employee health that should be taken into consideration when deciding to merge hospitals. This study illustrates the importance of analyzing the effects of mergers over several years and the need for more detailed analyses of merger processes and of the changes that may occur as a result of such mergers.

Objectives: To achieve international consensus across multiple specialties on a generic ultrasound rating scale using a Delphi technique., Methods: Ultrasound experts from Obstetrics-Gynaecology, Surgery, Urology, Radiology, Rheumatology, Emergency Medicine, and Gastro-Enterology representing North America, Australia, and Europe were identified. A multi-round survey was conducted to obtain consensus between these experts. Of 60 invited experts, 44 experts agreed to participate in the first Delphi round, 41 remained in the second round, and 37 completed the third Delphi round. Seven key elements of the ultrasound examination were identified from existing literature and recommendations from international ultrasound societies. All experts rated the importance of these seven elements on a five-point Likert scale in the first round and suggested potential new elements for the assessment of ultrasound skills. In the second round, the experts re-rated all elements and a third round was conducted to allow final comments. Agreement on which elements to include in the final rating scale was pre-defined as more than 80% of the experts rating an element four or five, on importance to the ultrasound examination., Results: Two additional elements were suggested by more than 10% of the experts in the first Delphi round. Consensus was obtained to include these two new elements along with five of the original elements in the final assessment instrument: 1) Indication for the examination 2) Applied knowledge of ultrasound equipment 3) Image optimization 4) Systematic examination 5) Interpretation of images 6) Documentation of examination and 7) Medical decision making., Conclusion: International multispecialty consensus was achieved on the content of a generic ultrasound rating scale. This is the first step to ensure valid assessment of clinicians in different medical specialties using ultrasound.

Purpose: The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS)., Materials and Methods: 39 patients (17 women and 22 men) with a total of 125 liver metastases were treated with percutaneous or intraoperative CEUS-guided MW ablation. The primary tumor was colorectal cancer (n = 31), breast cancer (n = 6), carcinoid tumor (n = 1), and gastrointestinal stromal tumor (GIST) (n = 1). The median number of metastases ablated in the 45 treatment sessions was 2 (range 1 - 11). The median size (maximum diameter) of the 125 metastases was 1.5 cm (range, 0.6 - 4.0 cm). Nineteen (15 %) of the 125 metastases were bigger than 2 cm. Metastases smaller than 2 cm were treated with a single needle, metastases bigger than 2 cm were treated with 2 or 3 parallel needles., Results: The 45 MW ablation sessions were performed percutaneously (n = 30), during laparotomy (n = 3), or during laparotomy combined with liver resection (n = 12). The 39 patients were followed up for at least 4 months with a median duration of 11 months (range, 4 - 20 months). The technical success rate was 100 %. The clinical effectiveness was 100 % with complete coverage of the metastasis by the avascular coagulation zone evaluated on immediate post-ablation CEUS. Local tumor progression (local recurrence) was seen in 12 (9.6 %) of the 125 treated metastases, and affected 10 (26 %) of the 39 patients. One major complication was observed in the form of a liver abscess that easily resolved after percutaneous drainage. Four minor complications were observed: Three cases of pain located at the puncture site and one case of ascites. CEUS was valuable in all phases of ablation including pre-ablation staging and procedure planning, placement of MW needles in the tumor, immediate post-ablation control of coagulation size, and finally in the long term follow-up regime., Conclusion: CEUS-guided MW ablation of liver metastases is an efficient and safe ablation technique with several advantages compared to other ablation modalities., (© Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study was to demonstrate and evaluate the ultrasound-guided drainage of deep pelvic abscesses in which transabdominal percutaneous access could not be performed because of overlying structures. A retrospective analysis of 32 consecutive patients with 33 deep pelvic abscesses was performed. The underlying causes of the abscesses included postsurgical fluid collection or surgical complications in 18 of the 32 patients, and 11 of these patients underwent recent rectal cancer surgery. The locations of the abscesses, which had a median diameter of 6 cm (range 2-10 cm), were as follows: perirectal (n=13), presacral (n=9), pouch of Douglas (n=7), internal genitals (n=2) and between the bowel loops (n=2). The abscesses were all drained using ultrasound (US) guidance with a transrectal (n=18), transvaginal (n=11), transperineal ( n=2) or transgluteal (n=2) approach. Of the larger abscesses (median diameter 7 cm), 19 were treated with catheter drainage and 18 of these cases resulted in favorable clinical outcomes. Of the smaller abscesses (median diameter 4 cm), 14 were treated with needle drainage. In two of these cases, follow-up US showed that a repeat puncture and drainage was necessary. All needle drainages resulted in favorable clinical outcomes. Sixteen of the 29 transrectal or transvaginal drainage procedures were performed without any anesthesia (10 were performed with a needle and six were performed with a catheter). Apart from minor discomfort during the drainage procedure and the subsequent in-dwelling catheter period, there were no serious complications related to the drainage procedures. We conclude that ultrasound-guided transrectal, transvaginal, transperineal and transgluteal drainage of deep pelvic abscesses are safe and effective treatment approaches. Based on our findings, needle drainage will be our most common first-line treatment approach because of the simplicity of the procedure, improved patient comfort and reduced costs. Catheter drainage will be reserved for large multiloculated abscesses., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

A 71-year-old man had a coarse needle biopsy performed. After the biopsy symptoms of abdominal bleeding were deteced. An acute ultrasound examination was performed as Focussed Assessment with Sonography in Trauma (FAST). The findings were inconclusive and a Contrast Enhanced Ultrasound (CEUS) was carried out. CEUS immediately demonstrated as well a rim around the liver with clear borders as a large amount of abdominal fluid. Upon these findings immediate surgery was performed. CEUS improves the contrast between areas with and without perfusion, which enhance the presence of haemorrhagic fluid, independently of the fluid's echo-pattern. CEUS seems to be a fast and valuable extension to FAST.

Background and Aim: Dendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(−) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b., Results: Of 46 patients who initiated treatment, 10 stopped treatment within 1-4 weeks because of rapid disease progression and deterioration. After 8 weeks, 36 patients were evaluable: no patient had an objective response, 11 patients had stable disease (SD); six had continued SD after 4 months, and three patients had prolonged SD for more than 6 months. The mean overall survival time was 9 months, with a significantly longer survival (18.4 months) of patients who attained SD compared with patients with progressive disease (PD) (5 months). Induction of antigen-specific T-cell responses was analyzed by multidimensional encoding of T cells using HLA-A2 major histocompatibility complex (MHC) multimers. Immune responses against five high-affinity vaccine peptides were detectable in the peripheral blood of six out of 10 analyzed HLA-A2+ patients. There was no observed correlation between the induction of immune responses and disease stabilization. A significant lower blood level of regulatory T cells (CD25(high) CD4 T cells) was demonstrable after six vaccinations in patients with SD compared with PD., Conclusions: Vaccination was feasible and safe. Treatment-associated SD was observed in 24% of the patients. SD correlated with prolonged survival suggesting a clinical benefit. Differences in the level of regulatory T cells among SD and PD patients could indicate a significant role of these immune suppressive cells.

In the presented case, liver metastases were not visible on conventional ultrasound imaging. After a contrast agent was given, multiple metastases were seen, and an ultrasound-guided biopsy was performed, guided by the contrast image.

Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients obtained disease stabilization (SD) for more than 8 weeks. An antigen-specific immune response was demonstrated in 6/6 patients tested. Furthermore, significant alterations in serum YKL-40 and IL-6 were found during treatment. In conclusion, DC vaccination in our setting is feasible and without severe toxicity. Almost half of the patients obtained SD, and in more than 1/3 of the patients, SD persisted for more than 6 months. However, the evaluation of SD is difficult to interpret in the absence of a randomized trial and, therefore, these results should be interpreted with caution. Antigen-specific immune responses were observed in a subset of the treated patients.

Purpose: To evaluate the effectiveness and safety of percutaneous radiologic gastrostomy (PRG) under ultrasonographic (US) and fluoroscopic guidance using a simplified gastropexy technique., Material and Methods: One hundred and fifty-four (154) patients (mean age 73, range 22-93 years) were referred for PRG. Indication for PRG was neurologic disease, head/neck cancer, and other disease in 73%, 15%, and 12%, respectively. Initially, the stomach was filled with 300-500 cm3 of tap water via a nasogastric tube. The fluid-filled stomach was punctured under US guidance. A guidewire and a single T-fastener were introduced. Under fluoroscopic guidance, the tract was dilated over the guidewire until a 16F dilator with a peel-away sheath could be introduced. During dilatation, the external suture string to the T-fastener was held tight to fixate the gastric wall. A 14F balloon-retained gastrostomy tube was introduced and inflated. The T-fastener was then released, and the gastrostomy tube was retracted gently to affix the gastric wall to the abdominal wall (tube gastropexy). Technical success was assured by aspiration of gastric fluid and fluoroscopically by injection of a water-soluble contrast medium., Results: The primary technical success rate was 98%. At 30-day follow-up, 3.2% had major complications and 14% minor complications. Three patients (1.9%) died of complications related to the procedure. Thirteen cases (8%) of simple tube displacement without other complications occurred., Conclusion: PRG guided by US and fluoroscopy is a relatively safe technique with a high success rate, provided the stomach can be properly distended with fluid. However, tube gastropexy alone does not seem to protect against early dislodgement.