These data indicate that survivals after transplantation for HEH are favorable. Given the propensity for recurrence after resection, these data support consideration of liver transplantation for all patients with significant intrahepatic tumor burden.
Cholangiocarcinoma is an aggressive malignancy with 5-year survival rates<15%. Selected patients present with localized but unresectable disease and are candidates for orthotopic liver transplantation (OLT). The purpose of this study was to evaluate a multi-institutional experience with liver transplantation for this malignancy. Two hundred eighty patients with cholangiocarcinoma treated with OLT from 1987 to 2005 were identified in The United Network for Organ Sharing database. Patient and allograft survivals were calculated and the potential prognostic value of multiple clinicopathologic variables was assessed. At a median follow-up interval of 452 days (range: 0-6,166 days), 1- and 5-year patient survivals were 74 and 38%, respectively, with 49 actual 5-year survivors and 21 actual 10-year survivors. Posttransplant 1- and 5-year allograft survivals were 69 and 36%, respectively. Study variables associated with improved survivals included diagnosis of cholangiocarcinoma pre-OLT [5-year overall survival (OS): 68 vs. 20% for patients with incidental diagnoses at the time of OLT, p<0.001] and OLT after 1993 (5-year OS: 45 vs. 30% pre-1994, p<0.01). In contrast, the diagnosis of concomitant primary sclerosing cholangitis did not impact survivals (5-year OS: 41 vs. 50% without primary sclerosing cholangitis, p=0.402). Selected cholangiocarcinoma patients treated with OLT experience a survival benefit. Diagnosis of cancer prior to OLT allows for better staging and pre-OLT therapy that may translate into improved outcomes. These data support the continued development of multimodality cholangiocarcinoma treatment protocols that include OLT.
In order to identify the earliest genetic changes that precipitate species formation, it is useful to study genetic incompatibilities that cause only mild dysfunction when incompatible alleles are combined in an interpopulation hybrid. Such hybridization within the nematode species Caenorhabditis briggsae has been suggested to result in selection against certain combinations of nuclear and mitochondrial alleles, raising the possibility that mitochondrial–nuclear (mitonuclear) epistasis reduces hybrid fitness. To test this hypothesis, cytoplasmic–nuclear hybrids (cybrids) were created to purposefully disrupt any epistatic interactions. Experimental analysis of the cybrids suggests that mitonuclear discord can result in decreased fecundity, increased lipid content, and increased mitochondrial reactive oxygen species levels. Many of these effects were asymmetric with respect to cross direction, as expected if cytoplasmic–nuclear Dobzhansky-Muller incompatibilities exist. One such effect is consistent with the interpretation that disrupting coevolved mitochondrial and nuclear loci impacts mitochondrial function and organismal fitness. These findings enhance efforts to study the genesis, identity, and maintenance of genetic incompatibilities that precipitate the speciation process.
Two strategies to increase the donor allograft pool for pediatric orthotopic liver transplantation (OLT) are deceased donor segmental liver transplantation (DDSLT) and living donor liver transplantation (LDLT). The purpose of this study is to evaluate outcomes after use of these alternative allograft types. Data on all OLT recipients between February 2002 and December 2004 less than 12 years of age were obtained from the United Network for Organ Sharing database. The impact of allograft type on posttransplant survivals was assessed. The number of recipients was 1260. Of these, 52% underwent whole liver transplantation (WLT), 33% underwent DDSLT, and 15% underwent LDLT. There was no difference in retransplantation rates. Immediate posttransplant survivals differed, with WLT patients having improved 30-day patient survivals compared to DDSLT and LDLT patients (P ϭ 0.004). Although unadjusted 1-year patient survivals were better for WLT versus DDSLT (P ϭ 0.01), after risk adjustment, 1-year patient survivals for WLT (94%), DDSLT (91%), and LDLT (93%) were similar (P values Ͼ 0.05). Unadjusted allograft survivals were better for WLT and LDLT in comparison with DDSLT (P ϭ 0.009 and 0.018, respectively); however, after adjustment, these differences became nonsignificant (all P values Ͼ 0.05). For patients Յ 2 years of age (n ϭ 833), the adjusted 1-year patient and allograft survivals were also similar (all P values Ͼ 0.05). In conclusion, in the current era of pediatric liver transplantation, WLT recipients have better immediate postoperative survivals. By 1 year, adjusted patient and allograft survivals are similar, regardless of the allograft type.
Pancreatic cancer is the deadliest of cancers, and effective diagnostic and therapeutic strategies are lacking. Global gene expression profiling holds promise for improved diagnosis and treatment. Knowledge of the location and timing of gene overexpression and the function of these genes, including their effects on signaling pathways, is important. These data may be used to develop histologic and serum biomarkers as well as to develop immunotherapeutic, molecular targeting, and gene therapy strategies. We have compiled a list of overexpressed genes in pancreatic cancer for which overexpression was confirmed by reverse transcriptase polymerase chain reaction, immunohistochemistry, and/or in situ hybridization following initial identification by global gene expression profiling. The techniques used in the determination of overexpression, problems encountered in global gene expression profiling, and the diagnostic and therapeutic implications of overexpression are discussed. The S100 gene family, mesothelin, prostate stem cell antigen, and 14-3-3 sigma, may have important clinical implications in pancreatic cancer diagnosis and treatment.
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