Aggressive local treatment for recurrent intrahepatic cholangiocarcinoma-Stereotactic radiofrequency ablation as a valuable addition to hepatic resection.

BACKGROUND: To evaluate the efficacy, safety and overall clinical outcome of local treatment for recurrent intrahepatic cholangiocellular carcinoma after hepatic resection. METHODS: Between 2007 and 2019 72 consecutive patients underwent hepatic resection for primary intrahepatic cholangiocellular carcinoma. If amenable, recurrent tumors were aggressively treated by HR or stereotactic radiofrequency ablation with local curative intent. Endpoints consisted of morbidity and mortality, locoregional and de novo recurrence, disease free survival, and overall survival. RESULTS: After a median follow-up of 28 months, recurrence of intrahepatic cholangiocellular carcinoma was observed in 43 of 72 patients undergoing hepatic resection (60.3%). 16 patients were subsequently treated by hepatic resection (n = 5) and stereotactic radiofrequency ablation (n = 11) with local curative intention. The remaining 27 patients underwent palliative treatment for first recurrence. Overall survival of patients who underwent repeated aggressive liver-directed therapy was comparable to patients without recurrence (p = 0.938) and was better as compared to patients receiving palliative treatment (p = 0.018). The 5-year overall survival rates for patients without recurrence, the repeated liver-directed treatment group and the palliative treatment group were 54.3%, 47.7% and 12.3%, respectively. By adding stereotactic radiofrequency ablation as an alternative treatment option, the rate of curative re-treatment increased from 11.9% to 37.2%. CONCLUSION: Repeated hepatic resection is often precluded due to patient morbidity or anatomical and functional limitations. Due to the application of stereotactic radiofrequency ablation in case of recurrent intrahepatic cholangiocellular carcinoma, the number of patients treated with curative intent can be increased. This leads to favorable clinical outcome as compared to palliative treatment of intrahepatic cholangiocellular carcinoma recurrence.

Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections.

Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 ± 39.0 ng/mL) and TCC (11.03 ± 8.52 µg/mL) in patients compared to healthy controls (p < 0.01 and p < 0.0001, respectively). Furthermore, systemic NETosis was significantly augmented in patients (5.87 (±3.71) × 106 neutrophils/mL) compared to healthy controls (0.82 (±0.74) × 106 neutrophils/mL) (p < 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections.

Ultrasound-Guided Fibrin Glue Injection for Treatment of Iatrogenic Femoral Pseudoaneurysms.

INTRODUCTION: Arterial pseudoaneurysms (PSAs) are the most common access site complication following transarterial catheter intervention. Ultrasound-guided injection of thrombogenic substances into perfused arterial PSAs followed by compression therapy is a well-established and less invasive treatment option than surgical repair. Different agents are available to induce thrombosis including thrombin and a fibrin-based tissue glue, which is used as first-line treatment at our institution. This paper deals with our experience using ultrasound-guided fibrin glue injection (UGFI). MATERIALS AND METHODS: Retrospective data analysis: all patients (55) treated for iatrogenic femoral PSA following digital subtraction angiography of the lower extremities between January 1, 2010, and December 31, 2018, were included. Data on epidemiology, PSA location and size, vascular risk factors, fibrin glue injection (fibrin glue volume), primary success rate of UFGI, and complications related to the treatment were analyzed. RESULTS: A total of 55 consecutive femoral iatrogenic PSAs were treated during the defined period and 32 (58.2%) of the patients were female. Imaging was performed using ultrasound in all cases. The most common PSA location (80.0%) was the common femoral artery, mean PSA size (± SD) was 2.7 ± 1.2 cm, and neck length was 1.6 ± 1.0 cm. The dose (mean ± SD) of fibrin glue was 2.6 mL (± 1.0; maximum: 6 mL). Primary UGFI success rate was 87.3% and conversion rate to open surgery was 12.7%. Two (4%) patients required embolectomy for peripheral embolization after UGFI. CONCLUSION: Early results achieved with UGFI for treatment of iatrogenic femoral PSA are promising. In our cohort, UGFI was a safe and effective first-line alternative to traditional open surgery, which then was unnecessary in the vast majority of PSA cases. Further prospective studies for comparison of ultrasound-guided techniques should be encouraged.

Improved non-calcified plaque delineation on coronary CT angiography by sonogram-affirmed iterative reconstruction with different filter strength and relationship with BMI.

PURPOSE: To prospectively compare non-calcified plaque delineation and image quality of coronary computed tomography angiography (CCTA) obtained with sinogram-affirmed iterative reconstruction (IR) with different filter strengths and filtered back projection (FBP). METHODS: A total of 57 patients [28.1% females; body mass index (BMI) 29.2±6.5 kg/m(2)] were investigated. CCTA was performed using 128-slice dual-source CT. Images were reconstructed with standard FBP and sinogram-affirmed IR using different filter strength (IR-2, IR-3, IR-4) (SAFIRE, Siemens, Germany). Image quality of CCTA and a non-calcified plaque outer border delineation score were evaluated by using a 5-scale score: from 1= poor to 5= excellent. Image noise, contrast-to-noise ratio (CNR) of aortic root, left main (LM) and right coronary artery, and the non-calcified plaque delineation were quantified and compared among the 4 image reconstructions, and were compared between different BMI groups (BMI <28 and ≥28). Statistical analyses included one-way analysis of variance (ANOVA), least significant difference (LSD) and Kruskal-Wallis test. RESULTS: There were 71.9% patients in FBP, 96.5% in IR-2, 96.5% in IR-3 and 98.2% in IR-4 who had overall CCTA image quality ≥3, and there were statistical differences in CCTA exam image quality score among those groups, respectively (P<0.001). Sixty-one non-calcified plaques were detected by IR-2 to IR-4, out of those 11 (18%) were missed by FBP. Plaque delineation score increased constantly from FBP (2.7±0.4) to IR-2 (3.2±0.3), to IR-3 (3.5±0.3) up to IR-4 (4.0±0.4), while CNRs of the non-calcifying plaque increased and image noise decreased, respectively. Similarly, CNR of aortic root, LM and right coronary artery improved and image noise declined from FBP to IR-2, IR-3 and IR-4. There were no significant differences of image quality and plaque delineation score between low and high BMI groups within same reconstruction (all P>0.05). Significant differences in image quality and plaque delineation scores among different image reconstructions both in low and high BMI groups (all P<0.001) were found. I4f revealed the highest image quality and plaque delineation score. CONCLUSIONS: IR offers improved image quality and non-calcified plaque delineation as compared with FBP, especially if BMI is increasing. Importantly, 18% of non-calcified plaques were missed with FBP. IR-4 shows the best image quality score and plaque delineation score among the different IR-filter strength.

Serum IGF-I is not a reliable pharmacodynamic marker of exogenous growth hormone activity in mice.

Serum IGF-I is a well-established pharmacodynamic marker of GH administration in humans and has been used for this purpose in animal studies. However, its general suitability in wild-type laboratory mice has not been demonstrated. Here we show that treatment with recombinant human GH (rhGH) in four different strains of laboratory mice increases body weight, lean body mass, and liver weight but does not increase hepatic expression and release of IGF-I. In contrast and as expected, hypophysectomized rats show a rapid increase in serum IGF-I after rhGH administration. The lack of IGF-I up-regulation in mice occurs despite hepatic activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and is not explained by GH dose, route of administration, origin of GH (i.e. recombinant human, bovine, and murine GH), treatment duration, genetic background, sex, or formation of neutralizing antibodies. Effects on other components of the GH/IGF pathway were highly influenced by genetic background and sex but not consistently affected by rhGH treatment. We conclude that IGF-I is not a reliable indicator of the biological effects of exogenous GH treatment in genetically and pharmacologically unmodified mice. We speculate that IGF-I release is already maximal in these animals and cannot be further increased by exogenous GH treatment. This is also suggested by the observation of restored IGF-I up-regulation in isolated murine hepatocytes after rhGH treatment. Total body weight, lean body mass, and liver weight may be more reliable phenotypic indicators in these models.