Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.
Importance With the increasing prevalence of hepatocellular carcinoma (HCC), ablative therapy is a critical treatment option to achieve a cancer-free state. The anatomic location of the tumor can be a challenge, and select hepatic locations of a tumor require laparoscopic-assisted strategies to safely reach and treat the lesion. Objective To assess the association of real-time ultrasonography-augmented navigation for HCC ablation with patient survival, operative time, and rate of incomplete ablations. Design, Setting, and Participants This retrospective case-control study was conducted among a prospectively collected database of more than 750 patients with HCC who were treated with ablation therapy with and without the use of navigation at a single quaternary medical center from June 2011 to January 2021. Data were analyzed from October 2022 through June 2023. Exposure Real-time ultrasonography-augmented navigation. Main Outcomes and Measures The primary outcome was rate of incomplete ablations in patients undergoing HCC ablation with vs without navigation. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and operative time. Results The analytic cohort included 467 patients (mean [SD] age, 62.4 [7.8] years; 355 male [76.0%]; 21 Hispanic [4.5%], 67 non-Hispanic Black [14.5%], and 347 Non-Hispanic White [75.0%] among 463 patients with race and ethnicity data). The most common etiology of liver disease was hepatitis C infection (187 patients with etiology data [40.0%]), and 348 of 458 patients with TMN staging data (76.0%) had TNM stage 1 disease. There were 187 individuals treated with navigation and 280 individuals treated without navigation. Patients who underwent navigation-assisted ablation were more likely to have stage 2 disease based on TNM staging (62 of 183 patients [33.9%] vs 47 of 275 patients [17.1%] with TMN data; P < .002) and had a higher mean (SD) number of lesions (1.3 [0.5] vs 1.2 [0.5] lesions; P = .002) and a longer mean (SD) operation time (113.2 [29.4] vs 109.6 [32.3] minutes; P = .04). Patients who underwent navigation were also more likely to have tumors in segment 8 (59 patients [32.1%] vs 53 of 275 patients with segment data [19.3%] with segment data; P = .005) and less likely to have tumors in segment 4 (20 patients [10.9%] vs 54 patients with segment data [19.6%]; P = .005). Overall mean (SD) time to recurrence after treatment was 10.0 (12.5) months, with similar rates for patients with navigation vs no navigation. There were no differences in incomplete ablation rate (10 patients [9.2%] vs 10 patients [10.5%]; P = .32), OS, or PFS between patients undergoing ablation with and without navigation. Conclusions and Relevance In this study, use of navigation was associated with comparable outcomes to undergoing ablation without navigation, although patients with navigation had more locally advanced disease. These findings suggest that use of real-time navigation in laparoscopic-assisted ablation of liver cancer should be considered as a useful tool for treating challenging tumors.
Minimally invasive operative approaches for resection and thermal ablation (eg, microwave, radiofrequency) of hepatocellular carcinoma (HCC) have been successfully implemented over the last two decades, although identifying tumors can be challenging. Successfully performing laparoscopic ablation requires real-time visualization and ultrasonography skills for direct placement of the ablation probe.In this study, we introduce a novel adjunct to ultrasound imaging for tumors located near or on the surface of the liver via intravenous delivery of indocyanine green (ICG) dye. Non-resectable lesion(s) not amenable to percutaneous ablation were considered for laparoscopic microwave ablation. Each patient initially received a dose of .3125 mg ICG via peripheral IV.A total of 17 patients were included. There was brisk uptake of ICG throughout the liver parenchyma in under 2 minutes in 15 of 17 patients; the remaining 2 required a second dose of ICG. In 14 cases, a hypo-fluorescent perfusion pattern in the tumor was clearly identified.Integrating ICG and fluorescent imaging provides a complementary adjunct to ultrasound in identifying HCC nodules. While previous applications of ICG typically require injections several days prior to surgery or segmental injections, this study demonstrates a novel real-time application of ICG to aid surgeons with various experiences in laparoscopic-assisted ablation procedures for HCC.
Water-blown polyurethane (PU) foams are of enormous technological interest as they are widely applied in various fields, i.e., consumer goods, medicine, automotive or aerospace industries. The discovery of the one-way shape-memory effect in PU foams provided a fresh impetus for extensive investigations on porous polymeric actuators over the past decades. High expansion ratios during the shape-recovery are of special interest when big volume changes are required, for example to fill an aneurysm during micro-invasive surgery or save space during transportation. However, the need to program the foams before each operation cycle could be a drawback impeding the entry of shape-memory polymeric (SMP) foams to our daily life. Here, we showed that a reversible shape-memory effect (rSME) is achievable for polyurethane water-blown semicrystalline foams. We selected commercially available crystallizable poly(ε-caprolactone)-diols of different molecular weight for foams synthesis, followed by investigations of morphology, thermal, thermomechanical and shape-memory properties of obtained compositions. Densities of synthesized foams varied from 110 to 180 kg∙m-3, while peak melting temperatures were composition-dependent and changed from 36 to 47 °C, while the melting temperature interval was around 15 K. All semicrystalline foams exhibited excellent one-way SME with shape-fixity ratios slightly above 100% and shape-recovery ratios from the second cycle of 99%. The composition with broad distribution of molecular weights of poly(ε-caprolactone)-diols exhibited an rSME of about 12% upon cyclic heating and cooling from Tlow = 10 °C and Thigh = 47 °C. We anticipate that our experimental study opens a field of systematic investigation of rSMEs in porous polymeric materials on macro and micro scale and extend the application of water-blown polyurethane foams to, e.g., protective covers with zero thermal expansion or even cushions adjustable to a certain body shape.
Background & Aims: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. Approach & Results: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15–0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13–4.73) and death (aHR 2.04, 95% CI: 1.44–2.88, p < 0.0001). Conclusions: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.
