The role of hepatic transplantation in patients with nonresectable liver or bile duct cancer remains a controversial issue. An analysis of 95 consecutive cases was undertaken to evaluate retrospectively the pathological tumor stage--in accordance with the TNM system--and outcome after transplantation. Included were patients with the following diagnoses: hepatocellular carcinoma (n = 52), cholangiocellular carcinoma (n = 10), hepatoblastoma (n = 2), hemangiosarcoma (n = 2), bile duct carcinoma (n = 20), and liver metastases from different primary tumors (n = 9). The overall actuarial survival rate at 5 years was 20.4%. Median survival improved significantly within the last 4 years as compared to the preceding era (18.06 vs. 4.0 months). Currently 27 patients are alive, with the longest follow-up more than 12 years. The incidences of residual or recurrent tumor were 27 and 28, respectively. Particularly in patients who underwent transplantation for hepatocellular or bile duct carcinoma without extra-hepatic tumor spread, the results were significantly better; median survival time achieved for these two groups were 120 (p less than 0.01) and 35 months (p less than 0.05). Prolonged survival without tumor recurrence was not seen in patients with cholangiocellular carcinoma or liver metastases. These results demonstrate clearly that liver transplantation for hepatobiliary malignancy is still justified on the premises of careful patient selection by adequate tumor staging.
Background-Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). Methods and Results-A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (nϭ1495) with subsequent replication in 2 additional samples (nϭ1157 and nϭ1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined Pϭ1.6ϫ10 Ϫ50 and 6.2ϫ10 Ϫ25 , respectively; nϭ4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (Pϭ0.009). Effects at the ABO locus were related to SNP rs657152 (combined Pϭ9.4ϫ10 Ϫ13 ). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; Pϭ2.2ϫ10 Ϫ6 ; rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; Pϭ9.4ϫ10 Ϫ6 ), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; Pϭ1.3ϫ10 Ϫ5 ). Conclusion-Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD. (Circ Cardiovasc Genet. 2010;3:331-339.)
In conclusion, FTY720 ameliorates the microcirculatory, biochemical, and histological manifestations of hepatic I/R injury by preventing T cell infiltration. These results indicate that T cells are pivotal mediators in hepatic I/R and may have important implications early after liver transplantation and in warm ischemia.
<b><i>Objectives:</i></b> We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes the<b><i></i></b>recommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. <b><i>Materials and Methods:</i></b> An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. <b><i>Results:</i></b> Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. <b><i>Conclusion:</i></b> Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.
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