The majority of patients with acute liver failure (ALF) die waiting for orthotopic liver transplantation (OLT). No other treatment modality is shown to improve survival. This study was conducted to assess the safety and feasibility of hepatocyte transplantation (HT) and subsequent engraftment and function of donor cells. Functional and structural integrity of cryopreserved and thawed human hepatocytes were assessed by their morphological characteristics, induction of P-4501A1 transcription, and survival in vivo by xenotransplantation into rats. Five patients with severe ALF underwent intrasplenic (4 patients) and/or intrahepatic (2 patients) HT through angiography under cyclosporine immunosuppression. All patients had grade III to IV encephalopathy and factor V levels less than 0.5 U/mL, were ventilator and dialysis dependent, and were not OLT candidates. Three of the 5 patients who survived 48 hours after HT had substantial improvement in encephalopathy scores, arterial ammonia levels, and prothrombin times. Clinical improvement was paralleled by an increase in aminopyrine and caffeine clearances. All 3 patients lived substantially longer than expected based on clinical experience after HT (12, 28, and 52 days) but eventually died. Postmortem examination showed the presence of transplanted hepatocytes in liver and spleen by light microscopy and fluorescent in situ hybridization (FISH). Cryopreserved and thawed human hepatocytes can be transplanted into recipients with ALF with some acceptable but definite complications. Engraftment of donor hepatocytes was proven by histological examination and FISH by both transjugular biopsy and at autopsy. Improvement in brain edema, encephalopathy grade, and clearance of antipyrine and caffeine suggested function, albeit with a 24- to 72-hour delay posttransplantation.
Important predictors of adverse outcomes of thrombosis in children, including postthrombotic syndrome (PTS), have recently been identified. Given this knowledge and the encouraging preliminary pediatric experience with systemic thrombolysis, we sought to retrospectively analyze our institutional experience with a thrombolytic regimen versus standard anticoagulation for acute, occlusive deep venous thrombosis (DVT) of the proximal lower extremities in children in whom plasma factor VIII activity and/or D-dimer concentration were elevated at diagnosis, from within a longitudinal pediatric cohort. Nine children who underwent the thrombolytic regimen and 13 who received standard anticoagulation alone were followed from time of diagnosis with serial clinical evaluation and standardized PTS outcome assessments conducted in uniform fashion. The thrombolytic regimen was associated with a markedly decreased odds of PTS at 18 to 24 months compared with standard anticoagulation alone, which persisted after adjustment for significant covariates of age and lag time to therapy (odds ratio
PURPOSE
Young individuals with occlusive, proximal limb DVT who have acutely elevated plasma levels of factor VIII and D-dimer are at high risk for post-thrombotic syndrome (PTS) when treated with conventional anticoagulation alone. We sought to evaluate our experience with adjunctive percutaneous mechanical/pharmacomechanical thrombolysis (PMT/PPMT) in such patients.
PATIENTS AND METHODS
Among 95 children 11 to 21 years of age enrolled in a prospective cohort of venous thromboembolism between March 1, 2006 and November 1, 2009, 16 met eligibility criteria and underwent PMT/PPMT, typically with adjunctive catheter-directed thrombolytic infusion (CDTI) of tissue-type plasminogen activator given post-procedure.
RESULTS
Median age was 16 years (range: 11–19 years). Thirteen cases (81%) involved lower limbs. Underlying stenotic lesions were disclosed in 53%, with endovascular stents deployed in all cases of May-Thurner. There were no peri-procedural major bleeding events and one symptomatic pulmonary embolism. Technical success rate was 94%. Early (<30 days) locally recurrent DVT developed in 40%, of which 83% were successfully re-lysed. Late recurrent DVT rate (median follow-up duration: 14 months [range: 1–42 months]) was 27%. Cumulative incidence of physically and functionally significant PTS at 1–2 years was 13%.
CONCLUSION
This experience provides prospective evidence that PMT/PPMT with adjunctive CDTI can be used safely and effectively in adolescents with DVT at high risk for PTS.
We retrospectively analyzed all listed patients having hepatic artery chemoembolization (HACE) for hepatocellular carcinoma (HCC) stage T2 or less. Outcomes were transplantation, waiting list removal, death, and HCC recurrence. Twenty patients (mean age 55.7 years; 15 males) were identified. Twelve (60%) were transplanted, seven (35%) were removed from the list and one (5%) remains listed. Fourteen (70%) are alive. All 12 transplanted patients are alive (mean 2.94 years); one of seven removed from the list is alive (mean 1.45 years). Survival was significantly higher for those transplanted or listed vs. removed from the list (100% vs. 14.3%, p = = 0.0002). No HCC's recurred. Three patients (15%) were removed from the list after prolonged waiting times before MELD. Hepatic artery chemoembolization induced deterioration and removal from the list of one (5%) patient. Survival for those transplanted was excellent(100%), but overall survival was significantly lower (61.3%) at a mean 5.48 years. Hepatic artery chemoembolization for listed patients with ≤ ≤ C = T2 stage HCC is beneficial, but must be weighed against decreased waiting times and risk of HACE-induced deterioration. This balance is influenced greatly by the MELD system's determination of waiting times for HCC patients.
Considering the inherent difficulties in identifying patients at risk for TAI and the effectiveness of chest CT as a screening tool for aortic injury, we recommend liberal use of chest CT in blunt chest trauma. Guidelines for determining the need for aortic imaging are outlined.
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