A Critical Role of the IL-22-IL-22 Binding Protein Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) ranks among the five most common cancer entities worldwide and leads to hundred-thousands of deaths every year. Despite some groundbreaking therapeutical revelations during the last years, the overall prognosis remains poor. Although the immune system fights malignant transformations with a robust anti-tumor response, certain immune mediators have also been shown to promote cancer development. For example, interleukin (IL)-22 has been associated with HCC progression and worsened prognosis in multiple studies. However, the underlying mechanisms of the pathological role of IL-22-signaling as well as the role of its natural antagonist IL-22 binding protein (IL-22BP) in HCC remain elusive. Here, we corroborate the pathogenic role of IL-22 in HCC by taking advantage of two mouse models. Moreover, we observed a protective role of IL-22BP during liver carcinogenesis. While IL-22 was mainly produced by CD4+ T cells in HCC, IL-22BP was abundantly expressed by neutrophils during liver carcinogenesis. Hepatocytes could be identified as a major target of this pathological IL-22-signaling. Moreover, abrogation of IL-22 signaling in hepatocytes in IL22ra1flox/flox × AlbCre+ mice reduced STEAP4 expression-a known oncogene-in HCC in vivo. Likewise, STEAP4 expression correlated with IL22 levels in human HCC samples, but not in healthy liver specimens. In conclusion, these data encourage the development of therapeutical approaches that target the IL-22-IL-22BP axis in HCC.

Bilateral Lung Artery Embolization Mimicking an Acute Myocardial Infarction.

Electrocardiographic abnormalities in patients with massive pulmonary embolism are common and unspecific. An 80-year-old woman was admitted to our department with severe respiratory insufficiency and hemodynamic instability. Abnormal high-sensitivity cardiac troponin I and ST-segmental elevation in II, III, aVF, and V3-V6 were present on admission. Segmental motion abnormalities of the left ventricular wall were not detectable in echocardiography. Instead, the presence of a right ventricular strain raised the suspicion of a lung artery embolization. The diagnosis was confirmed by a computed tomography of the chest, and a thrombolytic therapy with 100 mg recombinant tissue plasminogen activator (rt-PA) was administered. Though respiratory and hemodynamic stability were established, electromechanical disassociation suddenly occurred 30 hours later and the patient died. Electrocardiographic changes mimicking a myocardial infarction may occur after a massive pulmonary embolism and constitute a diagnostic challenge for clinicians being active in the field of emergency medicine and intensive care.

Accurate Orientation of the t-Branch Off-the-Shelf Multibranched Endograft After Deployment in Urgent Cases.

PURPOSE: To evaluate the orientation of the standardized off-the-shelf multibranched t-Branch after implantation in urgent thoracoabdominal aortic aneurysm (TAAA) repairs, to characterize the impact of branch malorientation on procedural success, and to identify any predictive factors associated with malorientation. METHODS: A retrospective analysis was conducted of 42 consecutive patients (mean age 73.3±7 years; 25 men) with urgent TAAA presentation treated with the t-Branch from January 2014 to June 2017. The primary objective was to quantify the preoperative clock position of the target vessels and determine any rotational deviation between the pre- and postoperative measurements and between the postoperative measurements and the standard branch configuration. Secondary outcomes were to identify factors influencing malorientation (>2 clock face hours) that could affect outcome. Results were compared for early (learning curve; n=18) vs late (n=24) experience and for adherence to (n=23) vs nonobservance of (n=19) the instructions for use (IFU). RESULTS: Technical success was 93% (39/42). No significant difference in rotational deviation was identified between patients treated within the IFU vs outside the IFU. Seven (17%) patients had at least one target vessel maloriented after the procedure, which was not associated with total procedure time, fluoroscopy time, contrast volume, radiation dose, or adherence to the IFU. Female gender was associated with increased rotational deviation in postprocedure measurement for the celiac trunk (p=0.044) and superior mesenteric artery (SMA; p=0.006). Female gender was also associated with increased rotational deviation between the branch origin after deployment and the standard configuration of the t-Branch for every target vessel [celiac trunk (p=0.005), SMA (p=0.001), right renal artery (p=0.037), and left renal artery (p=0.003)]. CONCLUSION: The implantation of the t-Branch device in urgent cases achieved accurate apposition without rotational deviation between the target vessels and the position of the endograft branches. Gender may have an impact on orientation of the device. The t-Branch appears to have a "forgiving" nature for higher malorientation with no effect on procedure time, target vessel revascularization, or early branch patency.

Early Outcomes of the t-Branch Off-the-Shelf Multibranched Stent-Graft in Urgent Thoracoabdominal Aortic Aneurysm Repair.

PURPOSE: To assess the short-term outcomes of the multibranched off-the-shelf t-Branch stent-graft for urgent thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the impact on outcomes of the learning curve and adherence to the instruction for use (IFU). METHODS: Between 2014 and 2017, 42 patients (mean age 73.3±7 years; 26 men) underwent urgent TAAA treatment using the t-Branch stent-graft [18 in the early (2014-2015) period and 24 in the late (2016-2017) period]. Nearly half the patients were symptomatic (n=18) and 12 had contained rupture. Aneurysm diameter >80 mm was present in 12 (mean diameter 77.7±13.2 mm). Nineteen patients did not meet the IFU for the t-Branch due to target vessel anatomy. The primary endpoints were spinal cord ischemia (SCI), renal function impairment, and 30-day mortality. Target vessel patency and endoleak incidence were assessed at 30 days. Multivariate analyses examined associations between perioperative variables and outcomes; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: The technical success rate was 93% (39/42). Successful catheterization was achieved in 150/155 target vessels (97%). The postoperative SCI rate was 21% (5 paraplegia/4 transient paraparesis) and was correlated with age (OR 1.26, 95% CI 1.01 to 1.56, p=0.04). The renal function impairment rate was 23% (10/42; 2 temporary, 2 permanent dialysis) and was correlated with early experience (OR 7.74, 95% CI 1.3 to 43.9, p=0.019). The 30-day mortality was 14% (no intraoperative deaths); no factor was associated with mortality. During the first month, the incidences of type I, II, and III endoleaks were 0%, 43%, and 0%, respectively; branch patency was 99% (150/151). Procedure time decreased in the later experience (479±333 vs 407±25 minutes, p=0.09), though it was increased in cases outside the IFU (497±135 vs 389±118 minutes, p=0.009), along with fluoroscopy time (121±48 vs 92±33 minutes, p=0.036). CONCLUSION: Endovascular repair of urgent TAAA using the t-Branch is a feasible treatment option with acceptable 30-day mortality and morbidity in terms of SCI and renal function impairment. Adherence to the IFU prolonged procedure time but had no effect on outcomes. Increased experience of such cases over time may improve outcomes.