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Portosystemic shunts can serve as a bridge to liver transplantation in patients with end-stage liver disease by providing portal decompression to treat life-threatening variceal bleeding and prevent recurrent episodes until an organ becomes available. The conventional TIPS procedure, however, is technically challenging to perform in infants due to the small size of their intrahepatic vasculature. We report two cases of emergent creation of portosystemic shunts as a bridge to liver transplantation in infants with life-threatening variceal bleeding using a conventional TIPS technique in the first case and a percutaneous DIPS technique in the other. Both procedures were successful at reducing the portosystemic pressure gradient and preventing further variceal bleeds until a liver transplant could be performed. The novel percutaneous DIPS procedure is a valuable alternative to the conventional TIPS in infants, as it is better suited for small or challenging intrahepatic vascular anatomy.

Purpose of review Orthotopic liver transplantation in the pediatric population is a technically challenging undertaking, requiring highly specialized surgical techniques unique to this group. This review describes the most current method of transplantation for these patients. Recent findings Pediatric liver transplantation employs multiple modifications of standard transplant technique, including alternative methods of vascular and biliary anastomoses as well as technical variant grafts. We herein describe how these methods are employed in procurement, back-table preparation, hepatectomy, and allograft implantation. Summary This review provides concise direction of surgical technique for pediatric liver transplant recipients.

A prognostic index to predict survival after liver transplantation could address several clinical needs. Here, we devised a scoring system that predicts recipient survival after pediatric liver transplantation. We used univariate and multivariate analysis on 4565 pediatric liver transplant recipients data and identified independent recipient and donor risk factors for posttransplant mortality at 3 months. Multiple imputation was used to account for missing variables. We identified five factors as significant predictors of recipient mortality after pediatric liver transplantation: two previous transplants (OR 5.88, CI 2.88-12.01), one previous transplant (OR 2.54, CI 1.75-3.68), life support (OR 3.68, CI 2.39-5.67), renal insufficiency (OR 2.66, CI 1.84-3.84), recipient weight under 6 kilograms (OR 1.67, CI 1.12-2.36) and cadaveric technical variant allograft (OR 1.38, CI 1.03-1.83). The Survival Outcomes Following Pediatric Liver Transplant score assigns weighted risk points to each of these factors in a scoring system to predict 3-month recipient survival after liver transplantation with a C-statistic of 0.74. Although quite accurate when compared with other posttransplant survival models, we would not advocate individual clinical application of the index.

Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities.

Although the incidence of caustic ingestion is declining, the management of caustic esophageal strictures remains a challenge. Mitomycin C (MMC) inhibits fibroblast proliferation and is effective in reducing scar in animal experiments. We report the case of a child with a distal esophageal stricture from lye ingestion managed with MMC. Despite repeated dilatations, at 1 year post injury, the stricture was 20% of esophageal diameter. Mitomycin C (4 microg/mL) was applied topically and circumferentially by endoscopy and repeated 4 months later. At 20 months follow-up, the child eats normally, and esophagram showed decreased stenosis (stricture was 50% of esophageal diameter). No complications were observed. Although controlled trials are required to confirm its efficacy, MMC should be considered as an adjunct in the management of caustic esophageal strictures in children.

Since the advent of the human genome, the era of personalized genomic medicine is indisputably in progress.In an effort to contribute to the evolving knowledge of genomic medicine, we have aimed directly at building a bioresource bank for hepatocellular carcinoma. This tumor bank is based on the rigorous guidelines set forth by the National Cancer Institute, and it offers analytes to help elucidate the mechanisms of progression from cirrhosis to malignancy, risk factors for recurrence, and applicability of current treatment options to a diverse group of people.Surgeons have a privileged position between patients (and their cancer) and the benches of basic science. Thus, we offer a primer based on our own experiences, from which surgeons may take elements to build their own bioresource bank for use in collaboration with others. We highlight some practicalities and pitfalls that could be overlooked, as well as a discussion of possible solutions.

Aim: Liver transplantations (LT) have proven to be a successful treatment for many tumors of the liver. The goal of this study was to evaluate the outcomes of liver transplantations in patients with primary liver tumors with a focus on rarer malignancies. Methods: The UNOS database catalogues all adult patients who underwent LT for a primary liver tumor from 1992-2008. Of the 73, 231 liver transplantations, 5,682 patients with liver tumors were identified and categorized by indication for LT: hepatocellular carcinoma (HCC, n=5272), hepatic epithelioid hemangioendothelioma (HEH, n=85), cholangiocarcinoma (n=249), sarcomas (n= 11) and combined HCC-Cholangiocarcinomas (HCC-CC, n=12). Survivals were calculated using Kaplan-Meier and log rank tests. Results: 5,629 patients received LT for solid liver tumors. HCC patients and their allografts survived longer than those transplanted for cholangiocarcinomas (p=0.001, 0.002) or for HCC-CC (p=0.025, 0.004). Overall survival rates of HCC patients were 86.4%, 71.3%, and 61.2% at 1, 3 and 5 years, respectively. Cholangiocarcinoma patients had survival rates of 79.7%, 60.3% and 45.5% at 1-, 3- and 5-years from transplant. HCC-CC patients had the worst overall survival of 72.9%, 39.1% and 39.1% at 1, 3 and 5 years. Allograft survival in HCC-CC patients was comparatively low, averaging 65.6%, 35.2% and 0% at 1-, 3- and 5-years. HEH patients and their allografts survived the longest with overall survival of 83.9%, 77.8% and 73.5% at 1, 3 and 5 years, respectively, and allograft survival at 76.8%, 69.8% and 64.3%. Conclusion: Our data reveals overall survival was significantly better in HEH patients when compared to HCC, cholangiocarcinoma and HCC-CC patients after LT. In fact, HCC-CC patients fared the worst, both in patient and allograft survival, as compared to HCC and HEH. Results of cholangiocarcinoma patients show worse survival after LT compared to HCC and HEH, though recent evidence suggests adjuvant therapy will change outcomes for the future. Our findings suggest transplantation for HCC-CC may not be sufficient treatment. Other forms of adjuvant and neoadjuvant therapy may be indicated, warranting further research.

Treatment for HEH does not follow a standardized algorithm. From clinical experience, it is assumed that pediatric patients with HEH will fare as well as other common pediatric liver tumors post-OLT. The UNOS dataset was examined for patients with pediatric OLT between 1987 and 2007. Patients were grouped into non-tumors, HB, HCC, HEH, and rare liver tumors. COD analysis was calculated using Fisher's exact test. Patient, allograft, and recurrence-free survival were compared using Kaplan-Meier curves and log-rank tests. A total of 366 patients with pediatric OLT were identified with primary liver tumors (HB - 237, HCC - 58, HEH - 35, other - 36). HEH patient survival (five yr: 60.6%) was poorer than non-tumor OLTpatient survival (five yr: 84.4%). Survival was worse when compared to HB (five yr: 72%) and rare liver tumors (five yr: 78.9%), but better than HCC (five yr: 53.5%). Allograft survival in HEH (five yr: 50.1%) lies between HB (five yr: 63.6%) and HCC (five yr: 42.8%). COD analysis demonstrates recurrence as a major cause in HB and HCC, but not for HEH or other liver tumors. The data suggest that patient survival may not be as high as previously believed and further investigation is warranted.

Hepatic solitary fibrous tumor (HSFT) is a very rare benign liver tumor without well-defined findings on imaging. Even with multiphase advanced contrast-enhanced liver imaging, a definitive preoperative diagnosis is impossible. The diagnostic process can be further complicated when there are two concurrent lesions with different radiologic appearances. Here, we compare the findings of a commonly encountered liver lesion, hepatic hemangioma, with those of an exceedingly rare lesion, HSFT.

Although the incidence of caustic ingestion is declining, the management of caustic esophageal strictures remains a challenge. Mitomycin C (MMC) inhibits fibroblast proliferation and is effective in reducing scar in animal experiments. We report the case of a child with a distal esophageal stricture from lye ingestion managed with MMC. Despite repeated dilatations, at 1 year post injury, the stricture was 20% of esophageal diameter. Mitomycin C (4 microg/mL) was applied topically and circumferentially by endoscopy and repeated 4 months later. At 20 months follow-up, the child eats normally, and esophagram showed decreased stenosis (stricture was 50% of esophageal diameter). No complications were observed. Although controlled trials are required to confirm its efficacy, MMC should be considered as an adjunct in the management of caustic esophageal strictures in children.

Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, especially in Asia, and regions of endemic hepatitis infection. The primary risk factors for HCC are chronic hepatitis infection by hepatitis C (HCV) or hepatitis B (HBV). We performed whole exome sequencing on 549 matched tumor and normal samples from three centers (BCM HGSC, RCAST, NCC) to identify somatic changes in protein coding regions and changes in copy number. Here we describe variants associated with specific viral etiologies in HCC. We found TP53, CTNNB1, ARID1A, ARID2, and AXIN1 to be among the most frequently mutated genes in the entire dataset, implicating DNA damage, WNT signaling, and chromatin remodeling as recurrently altered pathways in HCC. Our validation rate for mutations in significantly mutated genes was over 95%. We identified 18 genes which differed significantly (p < 0.05) in mutation frequency between viral subtypes. Of these, AXIN1 was mutated in over 15% of HBV-associated HCC but less than 5% of HCV and non-viral-associated HCC. Additionally, we performed GISTIC analysis based on read depth from our whole exome sequencing data. We found that WNT3A and MYC were significantly amplified and AXIN1 and TP53 were significantly deleted in HCV-associated HCC but not HBV or non-virus-associated HCC. Our findings indicate that WNT/beta-catenin signaling is a frequently altered pathway in HCC. While aberrations in this pathway were present in all viral etiologies, HBV-associated HCC tended to mutate AXIN1 while HCV-associated HCC tended to have AXIN1 deletion. These differences may result from virus-specific oncogenic processes. Citation Format: Kyle R. Covington, Lawrence A. Donehower, Chad Creighton, Betty L. Slagle, John A. Goss, Ronald T. Cotton, Marie-Claude Gingras, Eve Shinbrot, Jacfranz J. Guiteau, Thao N. Nguyen, Theresa R. Harring, Donna M. Muzny, Kimberly Walker, HarshaVardhan Doddapaneni, Richard A. Gibbs, Hiroyuki Aburatani, Tatsuhiro Shibata, David A. Wheeler, Japan ICGC HCC Project. Viral subtypes in hepatocellular carcinoma are associated with different mechanisms of WNT/CTNNB1 alteration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2211. doi:10.1158/1538-7445.AM2014-2211

Hepatoblastoma (HB) is the most common primary liver tumor in children and accounts for two-thirds of all malignant liver neoplasms in the pediatric population. For patients with advanced HB (unresectable or unresponsive to chemotherapy), combined treatment with chemotherapy and liver transplantation is an excellent option. The etiology of HB is mostly obscure because of its extreme rarity although some inherited syndromes and very low birth weight have been associated with it. The prognosis for children with HB has significantly improved in the past three decades thanks to advancements in chemotherapy, surgical resection and postoperative care. In 2002 a surgical staging system called pretreatment extent of disease (PRETEXT) was designed to allow a universal, multidisciplinary approach to patients with HB. Between one-third to two-thirds of patients initially present with unresectable tumors or distant metastases, but up to 85% of these tumors become operable after neoadjuvant chemotherapy. Patients with PRETEXT categories 1, 2, and some 3 are referred for neoadjuvant chemotherapy followed by surgical resection with the goal of complete tumor removal. Classic treatments regimens include a combination of cisplatin, fluorouracil, and vincristine or cisplatin and doxorubicin. Liver transplantation is the only treatment option for unresectable HB. In 2010 the pediatric end-stage liver disease, a pediatric-specific scoring system that determines a patient’s ranking on the liver transplant list, began to award additional “exception” points for patients with HB. We analyzed the Standard Transplant Analysis and Research dataset to assess the impact of changes in exception point criteria for HB on outcomes after liver transplantation at Texas Children’s Hospital in Houston, Texas. We found that patients who were listed for transplantation with current HB exception criteria experienced a shorter waitlist time but survival was similar between the two eras.

The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. The ever-expanding sequencing capacity ushered in by the second generation of DNA sequencers has enabled complete base-level description of the cancer genome and is therefore deepening our understanding of the etiology of the disease. We have combined a variety of approaches centered on next generation sequencing technologies aimed at comprehensive characterization of the cancer genome to define the key molecular lesions that drive tumor initiation and progression. These include targeted exonic sequencing to define coding sequence mutation, whole genome shotgun sequencing to define structural rearrangements, and cDNA sequencing to define alteration in expression levels, aberrant splicing and fusion transcripts. We have applied these approaches to pancreatic adenocarcinoma, hepatocellualr carcinoma and colorectal carcinoma. Results of genome sequencing have yielded an unprecedented picture of the rearrangements and mutations from analysis of read sequence and read coverage across the chromosomes. Evident in both the cancers is a dramatic reduction in SNP variation in the tumor genome compared to the germline from the same individual owing to extensive loss of heterozygosity. Superimposed on this are a few thousand mutations, some of which drive the tumor phenotype. The corresponding set of analog data generated by SNP-array microarray platforms provide validation of the central results from sequencing which leads to a new appreciation of the relationship between genetic change and the malignant phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2218.