The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Although liver transplantation is an effective means of treating selected patients, pretransplantation tumor progression may preclude some patients from undergoing transplantation. The aim of this study is to determine the safety and efficacy of percutaneous radiofrequency thermal ablation (RFA) in 33 consecutive patients with nonresectable HCC and advanced cirrhosis. Mean subject age was 57.2 ± 10.6 years, mean Child‐Turcotte‐Pugh score was 7.0 ± 1.4, and mean maximal tumor diameter was 3.6 ± 1.1 cm. Using contrast‐enhanced computed tomography and magnetic resonance imaging, 22 patients (66%) had a complete radiological response at 3 months post‐RFA, whereas 11 patients (33%) had an incomplete radiological response. During follow‐up, 18 patients (54%) experienced tumor progression and 9 subjects underwent repeated ablation for either residual disease or tumor progression. The overall actuarial patient survival rate of the 33 patients was 58% at 2 years, whereas the transplantation‐free patient survival rate was 34% at 2 years. Fifteen of 23 transplant candidates were successfully bridged to liver transplantation after a mean post‐RFA follow‐up of 7.9 ± 6. 7 months. The extent of tumor necrosis in the explant varied, but no subjects had evidence of tumor seeding on post‐RFA imaging, at liver transplantation, or in the explant. The 3‐year actuarial posttransplantation patient survival rate was 85%. Two patients have developed posttransplantation recurrence, and both had microscopic vascular invasion in their explants. In summary, our data show that RFA is a safe and effective treatment modality for patients with advanced cirrhosis and nonresectable HCC. Although the ability of RFA to prevent or delay tumor progression requires further prospective study, its favorable safety profile and promising efficacy make it an attractive treatment option for liver transplant candidates with nonresectable HCC.
These studies suggest that early and aggressive intima-media thickening (which is made up primarily of myofibroblasts) plays an important role in AV fistula stenosis in a pig model of AV fistula placement. Interventions that target the mechanisms and cellular phenotypes described in this model, may be effective in reducing the very significant morbidity and economic costs currently associated with AV fistula failure.
Venous stenosis is a significant problem in arteriovenous fistulae, likely due to anatomical configuration and wall shear stress profiles. To identify linkages between wall shear stress and the magnitude and pattern of vascular stenosis, we produced curved and straight fistulae in a pig model. A complete wall stress profile was calculated for the curved configuration and correlated with luminal stenosis. Computer modeling techniques were then used to derive a wall shear stress profile for the straight arteriovenous fistula. Differences in the wall shear stress profile of the curved and straight fistula were then related to histological findings. There was a marked inverse correlation between the magnitude of wall shear stress within different regions of the curved arteriovenous fistula and luminal stenosis in these same regions. There were also significantly greater differences in wall shear stress between the outer and inner walls of the straight as compared to curved arteriovenous fistula, which translated into a more eccentric histological pattern of intima-media thickening. Our results suggest a clear linkage between anatomical configuration, wall shear stress profiles, and the pattern of luminal stenosis and intima-media thickening in a pig model of arteriovenous fistula stenosis. These results suggest that fistula failure could be reduced by using computer modeling prior to surgical placement to alter the anatomical and, consequently, the wall shear stress profiles in an arteriovenous fistula.
Donation after cardiac death (DCD) is uncommon in part because clinicians cannot prospectively identify patients who are likely to die within 60 min of withdrawal of life-sustaining treatments (LST). UNOS criteria exist but have not been validated. Consecutive patients electively withdrawn from LST at five university-affiliated hospitals were prospectively enrolled. Demographic and treatment characteristics were collected. Chi-square was used to determine risk for death within 60 min and validate the UNOS criteria. A total of 533 patients were enrolled. A total of 28 were excluded from this report due to age <18 years or failure to include time of death. Of 505 (95%) patients, 227 (45%) died within 60 min, 134 (27%) in 1-6 h and 144 (29%) >6 h after withdrawal of LST. A total of 29%, 52%, 65% and 82% of patients with 0,1,2 and 3 UNOS DCD criteria, respectively, died within 60 min of withdrawal of LST. The data validate the UNOS criteria. Patients with no criteria might be excluded from consideration for DCD. Those with more than one criterion are reasonable candidates, while those with a single criterion should be considered if a 50% failure rate for DCD is acceptable.
We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.
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