ObjectiveThe authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. Summary Background DataThe efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. MethodsFrom May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-torecipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. ResultsMedian blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1 140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 (range, 53-90 kg). The body weights of four donors were less than those of the corresponding recipients and the lowest donor-to-recipient body weight ratio was 0.62:1 (donor, 41 kg; recipient, 66 kg). Pretransplant ManagementThe evaluation and management followed the same protocol as for any patient who was considered for transplantation in high-urgency status. All seven patients required admission to the intensive care unit before transplantation. In each case, moderate-to-severe hepatic encephalopathy was evident (Table 1) Surgical ProceduresThe donor hepatectomy (Fig. IA) consisted of an extended right lobectomy performed through a bilateral subcostal incision with median extension to the xyphoid. To avoid homologous blood transfusion, autologous blood was collected from the donor on induction of anesthesia, and a cell saver was used to collect blood lost during operation. Intraoperative ultrasound examination was performed to identify the major vascular structures of the liver. Special attention was paid to the anatomy of the junction of the middle and left hepatic veins and the possible existenc...

Poor prognosis of cancers, including hepatocellular carcinoma (HCC), is mainly associated with metastasis; however, the underlying mechanisms remain poorly understood. This article investigates the role of lysyl oxidase-like 2 (LOXL-2) in the biology of HCC metastasis. First, we showed that HCC metastasis relies on a collagen-modifying enzyme, LOXL2, which was significantly overexpressed in tumorous tissues and sera of HCC patients, indicating that LOXL2 may be a good diagnostic marker for HCC patients. Second, we delineated a complex, interlinked signaling network that involves multiple regulators, including hypoxia, transforming growth factor beta (TGF-b), and microRNAs (miRNAs), converging to control the expression of LOXL2. We found not only that LOXL2 was regulated by hypoxia/hypoxia-inducible factor 1 alpha (HIF-1a), but also that TGF-b activated LOXL2 transcription through mothers against decapentaplegic homolog 4 (Smad4), whereas two frequently underexpressed miRNA families, miR-26 and miR-29, cooperatively suppressed LOXL2 transcription through interacting with the 3' untranslated region of LOXL2. Third, we demonstrated the imperative roles of LOXL2 in modifying the extracellular matrix components in the tumor microenvironment and metastatic niche of HCC. LOXL2 promoted intrahepatic metastasis by increasing tissue stiffness, thereby enhancing the cytoskeletal reorganization of HCC cells. Furthermore, LOXL2 facilitated extrahepatic metastasis by enhancing recruitment of bone-marrow-derived cells to the metastatic site. Conclusion: These findings integrate the clinical relevance, molecular regulation, and functional implications of LOXL2 in HCC metastasis. (HEPATOLOGY 2014;60:1645-1658 H epatocellular carcinoma (HCC) is the most common form of primary liver cancer. HCC is the fifth-most prevalent cancer and ranked the second-most common lethal cancer.1 It claims more than 600,000 lives globally every year. 1 The high mortality rate in HCC is mainly attributable to metastasis for at least three reasons. First, it is a major cause of liver and organ failure. Second, patients diagnosed

A population of stromal cells, myeloid-derived suppressor cells (MDSCs), is present in tumors. Though studies have gradually revealed the protumorigenic functions of MDSCs, the molecular mechanisms guiding MDSC recruitment remain largely elusive. Hypoxia, O 2 deprivation, is an important factor in the tumor microenvironment of solid cancers, whose growth often exceeds the growth of functional blood vessels. Here, using hepatocellular carcinoma as the cancer model, we show that hypoxia is an important driver of MDSC recruitment. We observed that MDSCs preferentially infiltrate into hypoxic regions in human hepatocellular carcinoma tissues and that hypoxia-induced MDSC infiltration is dependent on hypoxia-inducible factors. We further found that hypoxia-inducible factors activate the transcription of chemokine (C-C motif) ligand 26 in cancer cells to recruit chemokine (C-X3-C motif) receptor 1-expressing MDSCs to the primary tumor. Knockdown of chemokine (C-C motif) ligand 26 in cancer cells profoundly reduces MDSC recruitment, angiogenesis, and tumor growth. Therapeutically, blockade of chemokine (C-C motif) ligand 26 production in cancer cells by the hypoxia-inducible factor inhibitor digoxin or blockade of chemokine (C-X3-C motif) receptor 1 in MDSCs by chemokine (C-X3-C motif) receptor 1 neutralizing antibody could substantially suppress MDSC recruitment and tumor growth. Conclusion: Cancer cells direct MDSC homing to primary tumor, suggesting that targeting MDSC recruitment represents an attractive therapeutic approach against solid cancers. (HEPATOLOGY 2016;64:797-813) H epatocellular carcinoma (HCC) is the fifth most common and the second most lethal malignancy in the world. Prognosis of HCC remains poor due to late symptom presentation and lack of efficient treatments. (1) The most promising curative HCC treatments are surgical resection and liver transplantation, which are feasible only for less than 30% of patients due to poor liver function or metastasis. (2) Sorafenib, the only Food and Drug Administrationapproved drug for HCC treatment, extends survival of patients for less than 3 months. (3) Thus, new HCC therapeutic strategies are much warranted.Myeloid-derived suppressor cells (MDSCs), a population of bone marrow-derived myeloid progenitors, are present in the tumors of patients and highly protumorigenic. (4)(5)(6) In humans, they are mainly Abbreviations: Ab, antibody; CA5/CA9, carbonic anhydrases V and IX; CCL26, chemokine (C-C motif) ligand