A preoperative magnetic resonance imaging can aid in staging and treatment choice for upper tract urothelial carcinoma.

Objectives: The aim was to investigate the predictive abilities of a preoperative diffusion-weighted MRI (dwMRI) among patients with surgically treated upper tract urothelial carcinoma (UTUC). Materials and methods: Written consent was obtained from all participants in this prospective and ethically approved study. Thirty-five UTUC patients treated with radical surgery were examined with a preoperative dwMRI and prospectively included during 2017-2022. Two radiologists examined the CT scans and dwMRIs for radiological stage, and the apparent diffusion coefficient (ADC) in the tumours at the dwMRI was registered. The radiologists were blinded for patient history, final histopathology and the readings of the other radiologist. The radiological variables were analysed regarding their abilities to predict muscle-invasive disease (MID, T2-T4) and tumour grade at final pathology after radical surgery. The predictive abilities were assessed using chi-square tests, Student's t-test and calculating the area under the curve in a receiver operating characteristic (ROC) curve. Correlation between the two radiologists was quantified calculating the intra-class correlation coefficient. P-values <0.05 were considered statistically significant. Results: Mean age was 72 years, 20 had high-grade tumour, and 13 patients had MID. The ADC values at the dwMRI were significantly lower among patients with MID compared to patients with non-muscle-invasive disease (930 vs 1189, p = <0.001). The area under the ROC curve (AUC) in an ROC curve to predict MID was 0.88 (CI 0.77-0.99, p = <0.001). The ADC values were significantly lower among patients with high-grade tumours compared to low-grade tumours (1005 vs 1210, p = 0.002). The correlation of the ADC measurements between the two radiologists was of 0.93 (CI 0.85-0.96, p < 0.001). Conclusion: Tumour ADC at the MRI emerges as a potential biomarker for aggressive disease. The results are promising but should be validated in a larger, multicentre study.

EUS-guided coil placement for acute gastric variceal bleeding induced by non-EUS-guided variceal glue injection (with video).

Background and study aims Endoscopic ultrasound (EUS)-guided coil placement is a new emerging technique for management of gastric varices. In this video case report, we describe an EUS-guided coil placement for managing acute bleeding of gastric varices, following an unsuccessful glue injection to achieve hemostasis.

Impaired lymphatic function accelerates cancer growth.

Increased lymphangiogenesis is a common feature of cancer development and progression, yet the influence of impaired lymphangiogenesis on tumor growth is elusive. C3HBA breast cancer and KHT-1 sarcoma cell lines were implanted orthotopically in Chy mice, harboring a heterozygous inactivating mutation of vascular endothelial growth factor receptor-3, resulting in impaired dermal lymphangiogenesis. Accelerated tumor growth was observed in both cancer models in Chy mice, coinciding with reduced peritumoral lymphangiogenesis. An impaired lymphatic washout was observed from the peritumoral area in Chy mice with C3HBA tumors, and the number of macrophages was significantly reduced. While fewer macrophages were detected, the fraction of CD163+ M2 macrophages remained constant, causing a shift towards a higher M2/M1 ratio in Chy mice. No difference in adaptive immune cells was observed between wt and Chy mice. Interestingly, levels of pro- and anti-inflammatory macrophage-associated cytokines were reduced in C3HBA tumors, pointing to an impaired innate immune response. However, IL-6 was profoundly elevated in the C3HBA tumor interstitial fluid, and treatment with the anti-IL-6 receptor antibody tocilizumab inhibited breast cancer growth. Collectively, our data indicate that impaired lymphangiogenesis weakens anti-tumor immunity and favors tumor growth at an early stage of cancer development.

Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema.

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling--predominantly collagen and fat deposition--may dictate tissue swelling and govern interstitial transport in lymphedema.

Isolation of interstitial fluid from skeletal muscle and subcutis in mice using a wick method.

Until recent years, mice were sparsely used in physiological experiments, and therefore, data on the basic cardiovascular parameters of mice are lacking. Our aim was to gain access to interstitial fluid and thereby study transcapillary fluid dynamics in this species. Using a modified wick method, we were able to isolate interstitial fluid from subcutis and skeletal muscle in mice. Three-stranded, dry, nylon wicks were inserted post mortem in an attempt to avoid local inflammation and thus eliminate protein extravasation and wick contamination. Colloid osmotic pressure (COP) was measured with a colloid osmometer for submicroliter samples and averaged (means +/- SE) 18.7 +/- 0.4 in plasma, 9.1 +/- 0.4 in subcutis, and 12.3 +/- 0.5 mmHg in muscle. HPLC of plasma and wick fluid showed similar patterns except for some minor peaks eluting in the <40-kDa region. Plasma protein extravasation as determined by 125I-labeled human serum albumin showed that contamination of wick fluid by plasma proteins was negligible (<2%). Capillary hyperfiltration induced by intravenous infusion of saline (10% of body wt) was reflected in tissue fluid isolated by wicks as shown by the average postinfusion COP values of 14.5 +/- 0.6, 6.8 +/- 0.3, and 7.7 +/- 0.4 mmHg in plasma, subcutis, and muscle, respectively. We conclude that the wick technique can be easily adapted for use in mice and may represent a reliable method to isolate interstitial fluid and study transcapillary fluid flux in this species.