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Purpose: Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer. Multimodal treatment strategies are frequently necessary to achieve total tumor elimination. This study examines the efficacy of liver resection combined with local ablative therapy in comparison to liver resection only, in the treatment of patients with ≥ 4 CRLM. Methods: This retrospective cohort study was conducted at the University Hospital RWTH Aachen, Germany. Patients with ≥ 4 CRLM in preoperative imaging, who underwent curative resection between 2010–2021, were included. Recurrent resections and deaths in the early postoperative phase were excluded. Ablation modalities included radiofrequency or microwave ablation, and irreversible electroporation. Differences in overall- (OS) and recurrence-free-survival (RFS) between patients undergoing combined resection-ablation vs. resection only, were examined. Results: Of 178 included patients, 46 (27%) underwent combined resection-ablation and 132 (73%) resection only. Apart from increased rates of adjuvant chemotherapy in the first group (44% vs. 25%, p = 0.014), there were no differences in perioperative systemic therapy. Kaplan–Meier and log-rank test analyses showed no statistically significant differences in median OS (36 months for both, p = 0.638) or RFS (9 months for combined resection-ablation vs. 8 months, p = 0.921). Cox regression analysis showed a hazard ratio of 0.891 (p = 0.642) for OS and 0.981 (p = 0.924) for RFS, for patients undergoing resection only. Conclusion: For patients with ≥ 4 CRLM, combined resection-ablation is a viable option in terms of OS and RFS. Therefore, combined resection-ablation should be considered for complete tumor clearance, in patients with multifocal disease. [ABSTRACT FROM AUTHOR]

Purpose: To examine the safety and short-term oncologic outcomes of computer-tomography-guided (CT-guided) irreversible electroporation (IRE) of recurrent, irresectable colorectal liver metastases (CRLM) after major hepatectomy deemed unsuitable for thermal ablation. Patients and Methods: Twenty-three patients undergoing CT-guided IRE of recurrent CRLM after major hepatectomy were included in this study. All tumors were located adjacent to sole remaining intrahepatic blood vessels and bile ducts, precluding thermal ablation. Patients underwent systematic clinical and imaging follow-up, including magnetic resonance imaging of the liver at 1-month and 3-month intervals thereafter. Time to local and intrahepatic tumor progression within 12 and 36 months and associated risk factors were assessed using Kaplan Meier and Cox regression analysis, respectively. Results: Complete ablation with a safety margin of at least 0.5 cm was achieved in 22/23 (95.6%) patients. No vessel injury or thrombosis occurred. Five patients developed moderate biliary stenosis after a median of 4 weeks, without requiring treatment. Local tumor-progression-free rates within 12/36 months were 64%/57.4%, respectively. Intrahepatic-progression-free rate within 12/36 months was 36.4%/19.5%, respectively. Five (23%) patients were tumor-free at the end of follow-up. Multivariate Cox regression analysis did not show any association between local tumor-progression-free rates and patient age, target tumor size, primary tumor side or synchronicity of liver metastases. Conclusion: In this highly selected patient population with local recurrences of CRLM after major surgery, IRE was shown to be a safe salvage treatment option when thermal ablation is unsuitable. [ABSTRACT FROM AUTHOR]

Objective: The aim of this prospective randomised trial was to assess the impact of the team-based learning approach on basic musculoskeletal ultrasound skills in comparison to both peer-assisted and conventional teaching and to examine the influence of gender and learning style on learning outcomes. Methods: In this prospective randomised trial, we randomly assigned 88 students to 3 groups: team-based learning (n = 19), peer-assisted learning (n = 36) and conventional teaching (n = 33). Pre-existing knowledge was assessed using a multiple-choice (MC) exam. Student performance after completing the course was measured using an Objective Structured Clinical Examination (OSCE) and a second MC exam. Students were asked to complete Kolb's Learning Style Inventory and to evaluate the course. Results: There was a significant gain in theoretical knowledge for all students (p < 0.001). The team-based learning groups' performance proved to be significantly superior on the OSCE (p = 0.001). As gender had no significant effect on practical or theoretical performance, learning style was linked to differences in the practical outcome. An evaluation showed overall satisfaction with the course and with the respective teaching methods. Conclusion: Team-based learning proved to be superior to peer-assisted and conventional teaching of musculoskeletal ultrasound skills. [ABSTRACT FROM AUTHOR]

Purpose: To compare technical parameters and success of recanalization of celiac (CA) or superior mesenteric artery (SMA) with usage of steerable vs not steerable introducer sheaths. Methods: A retrospective analysis was performed on all consecutive patients who underwent recanalization with stent implantation of CA or SMA between 2015 and 2019. Data regarding technical success (successful stent placement with restoration of sufficient blood flow by the first attempt without changing kind of introducer sheath or access site), indication for treatment, vascular access, kind of introducer sheath, fluoroscopy time and radiation dose were collected. Preinterventional CT were analyzed to classify the difficulty of catheterization of target vessels. Technical parameters were compared with independent t-test (p ≤ 0.05). Results: 66 patients underwent recanalization of CA or SMA. Usage of steerable introducer sheaths was associated with higher technical success compared to not steerable introducer sheaths with transfemoral approach respectively of 8/8 vs 15/19 for the CA and 11/11 vs 17/20 for the SMA. Steerable introducer sheaths were used in recanalization considered more technically difficult compared to not steerable introducer sheaths (58% vs 33%). Usage of steerable introducer sheath showed a statistically significant reduction of radiation dose in the recanalization of the SMA (respectively 32035 ± 15716 cGy cm2 vs 60102 ± 28432 cGy cm2; p = 0.005). Conclusion: Even if used in more difficult interventions, steerable introducer sheaths showed a higher technical success compared to not steerable introducer sheaths with transfemoral access. [ABSTRACT FROM AUTHOR]

Objective: Beyond static assessment, functional techniques are increasingly applied in magnetic resonance imaging (MRI) studies. Stress MRI techniques bring together MRI and mechanical loading to study knee joint and tissue functionality, yet prototypical axial compressive loading devices are bulky and complex to operate. This study aimed to design and validate an MRI-compatible pressure-controlled varus–valgus loading device that applies loading along the joint line. Methods: Following the device's thorough validation, we demonstrated proof of concept by subjecting a structurally intact human cadaveric knee joint to serial imaging in unloaded and loaded configurations, i.e. to varus and valgus loading at 7.5 kPa (= 73.5 N), 15 kPa (= 147.1 N), and 22.5 kPa (= 220.6 N). Following clinical standard (PDw fs) and high-resolution 3D water-selective cartilage (WATSc) sequences, we performed manual segmentations and computations of morphometric cartilage measures. We used CT and radiography (to quantify joint space widths) and histology and biomechanics (to assess tissue quality) as references. Results: We found (sub)regional decreases in cartilage volume, thickness, and mean joint space widths reflective of areal pressurization of the medial and lateral femorotibial compartments. Discussion: Once substantiated by larger sample sizes, varus–valgus loading may provide a powerful alternative stress MRI technique. [ABSTRACT FROM AUTHOR]

The muscle specific isoform of the supervillin protein (SV2), encoded by the SVIL gene, is a large sarcolemmal myosin II- and F-actin-binding protein. Supervillin (SV2) binds and co-localizes with costameric dystrophin and binds nebulin, potentially attaching the sarcolemma to myofibrillar Z-lines. Despite its important role in muscle cell physiology suggested by various in vitro studies, there are so far no reports of any human disease caused by SVIL mutations. We here report four patients from two unrelated, consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. All patients showed increased levels of serum creatine kinase but no or minor muscle weakness. Mild cardiac manifestations were observed. Muscle biopsies showed complete loss of large supervillin isoforms in muscle fibres by western blot and immunohistochemical analyses. Light and electron microscopic investigations revealed a structural myopathy with numerous lobulated muscle fibres and considerable myofibrillar alterations with a coarse and irregular intermyofibrillar network. Autophagic vacuoles, as well as frequent and extensive deposits of lipoproteins, including immature lipofuscin, were observed. Several sarcolemma-associated proteins, including dystrophin and sarcoglycans, were partially mis-localized. The results demonstrate the importance of the supervillin (SV2) protein for the structural integrity of muscle fibres in humans and show that recessive loss-of-function mutations in SVIL cause a distinctive and novel myopathy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate signal changes in T2-weighted magnetic resonance imaging of liver metastases under treatment with and without bevacizumab-containing chemotherapy and to compare these signal changes to tumor contrast enhancement. Materials and methods: Retrospective analysis of 44 patients, aged 36–84 years, who underwent liver magnetic resonance imaging including T2-weighted and dynamic contrast enhancement sequences. Patients received bevacizumab-containing (n = 22) or conventional cytotoxic chemotherapy (n = 22). Magnetic resonance imaging was obtained at baseline and at three follow-ups (on average 3, 6 and 9 months after initial treatment). Three independent readers rated the T2 signal intensity and the relative contrast enhancement of the metastases on a 5-point scale. Results: T2 signal intensity of metastases treated with bevacizumab showed a significant (p<0.001) decrease in T2 signal intensity after initial treatment and exhibit compared to conventionally treated metastases significantly (p<0.001 for each follow-up) hypointense (bevacizumab: 0.70 ± 0.83 before vs. -1.55 ± 0.61, -1.91 ± 0.62, and -1.97 ± 0.52; cytotoxic: 0.73 ± 0.79 before vs. -0.69 ± 0.81, -0.71 ± 0.68, and -0.75 ± 0.65 after 3, 6, and 9 months, respectively). T2 signal intensity was strongly correlated with tumor contrast enhancement (r = 0.71; p<0.001). Intra-observer agreement for T2-signal intensity was substantial (κ = 0.75). The agreement for tumoral contrast enhancement between the readers was considerably lower (κ = 0.39). Conclusion: Liver metastases exhibit considerably hypointense in T2-weighted imaging after treatment with bevacizumab, in contrast to conventionally treated liver metastases. Therefore, T2-weighted imaging seems to reflect the effect of bevacizumab. [ABSTRACT FROM AUTHOR]

The aim of this study was to correlate the pre-procedural magnetic-resonance-imaging-based hepatic fat fraction (hFF) with the degree of hypertrophy after portal vein embolization (PVE) in patients with colorectal cancer liver metastases (CRCLM). Between 2011 November and 2020 February, 68 patients with CRCLM underwent magnetic resonance imaging (MRI; 1.5 Tesla) of the liver before PVE. Using T1w chemical shift imaging (DUAL FFE), the patients were categorized as having a normal (<5%) or an elevated (>5%) hFF. The correlation of hFF, age, gender, initial tumor mass, history of chemotherapy, degree of liver hypertrophy, and kinetic growth rate after PVE was investigated using multiple regression analysis and Spearman's test. A normal hFF was found in 43/68 patients (63%), whereas 25/68 (37%) patients had an elevated hFF. The mean hypertrophy and kinetic growth rates in patients with normal vs. elevated hFF were 24 ± 31% vs. 28 ± 36% and 9 ± 9 % vs. 8 ± 10% (p > 0.05), respectively. Spearman's test showed no correlation between hFF and the degree of hypertrophy (R = −0.04). Multivariable analysis showed no correlation between hFF, history of chemotherapy, age, baseline tumor burden, or laterality of primary colorectal cancer, and only a poor inverse correlation between age and kinetic growth rate after PVE. An elevated hFF in a pre-procedural MRI does not correlate with the hypertrophy rate after PVE and should therefore not be used as a contraindication to the procedure in patients with CRCLM. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan–Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2–10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3–40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015). [ABSTRACT FROM AUTHOR]