Whose national emergency? Caboolture and Kirribili? or Milikapiti and Mutitjulu?

Keynote Address - Ms Marion Scrymgour MLA Member for Arafura, Northern Territory Government. Other Speakers - Professor Gavin Brown AO FAA, Vice-Chancellor and Principal, University of Sydney; Mr Neville Perkins OAM, Master of Ceremonies; Mr Charles Madden, Welcome to country; Ms Michelle Blanchard, Acting Director, Koori Centre; Mr Nicholas Beeton, Ms Kerry Wallace-Massone, Ms Jade Swan Prize winners, Dr Charles Perkins AO Annual Memorial Prize

Prolactin receptor is a negative prognostic factor in patients with squamous cell carcinoma of the head and neck

Background: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs). Methods: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro. Results: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14–12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment. Conclusion: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs

Future liver remnant portal or hepatic vein reconstruction at stage I of ALPPS-How far can we push the boundaries?

Preservation of the future liver remnant (FLR) vascular integrity has always been considered crucial to achieving successful liver growths after major hepatectomies. Most surgeons appeared therefore reluctant to combine stage I of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) with vascular reconstructions. Here we describe a case series, where we combine parenchymal transection and venous in- or outflow reconstruction of the FLR at stage I of ALPPS. In addition, the cold flush of the FLR or delayed portal vein embolization is applied in selected cases

Meta-analysis of associating liver partition with portal vein ligation and portal vein occlusion for two-stage hepatectomy

BACKGROUND: Discussion is ongoing regarding whether associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) or portal vein occlusion is better in staged hepatectomy. The aim of this study was to compare available strategies using a two-stage approach in extended hepatectomy. METHODS: A literature search was performed in MEDLINE, Scopus, the Cochrane Library and Embase, and additional articles were identified by hand searching. Data from the international ALPPS registry were extracted. Clinical studies reporting volumetric changes, mortality, morbidity, feasibility of the second stage and tumour-free resection margins (R0) in two-stage hepatectomy were included. RESULTS: Ninety studies involving 4352 patients, including 320 from the ALPPS registry, met the inclusion criteria. Among these, nine studies (357 patients) reported on comparisons with other strategies. In the comparison of ALPPS versus portal vein embolization (PVE), ALPPS was associated with a greater increase in the future liver remnant (76 versus 37 per cent; P < 0·001) and more frequent completion of stage 2 (100 versus 77 per cent; P < 0·001). Compared with PVE, ALPPS had a trend towards higher morbidity (73 versus 59 per cent; P = 0·16) and mortality (14 versus 7 per cent; P = 0·19) after stage 2. In the non-comparative studies, complication rates were 39 per cent in the PVE group, 47 per cent in the portal vein ligation (PVL) group and 70 per cent in the ALPPS group. After stage 2, mortality rates were 5, 7 and 12 per cent respectively. CONCLUSION: ALPPS is associated with greater future liver remnant hypertrophy and a higher rate of completion of stage 2, but this may be at the price of greater morbidity and mortality

Antihypoxic potentiation of standard therapy for experimental colorectal liver metastasis through myo-inositol trispyrophosphate

PURPOSE: Tumor hypoxia activates hypoxia-inducible factors (Hifs), which induce a range of malignant changes including vascular abnormalities. Here, we determine whether inhibition of the hypoxic tumor response through myo-inositol trispyrophosphate (ITPP), a compound with antihypoxic properties, is able to cause prolonged vascular normalization that can be exploited to improve standard-of-care treatment. EXPERIMENTAL DESIGN: We tested ITPP on two syngeneic orthotopic mouse models of lethal colorectal cancer liver metastasis. Tumors were monitored by MRI and analyzed for the hypoxic response and their malignant potential. A Hif activator and in vitro assays were used to define the working mode of ITPP. Hypoxic response and vasculature were re-evaluated 4 weeks after treatment. Finally, we determined survival following ITPP monotherapy, FOLFOX monotherapy, FOLFOX plus Vegf antibody, and FOLFOX plus ITPP, both overlapping and sequential. RESULTS: ITPP reduced tumor load, efficiently inhibited the hypoxic response, and improved survival. These effects were lost when mice were pretreated with a Hif activator. Its immediate effects on the hypoxic response, including an apparent normalization of tumor vasculature, persisted for at least 4 weeks after treatment cessation. Compared with FOLFOX alone, Vegf antibody combined with FOLFOX prolonged survival by 140%, regardless of whether FOLFOX was given in overlap or after ITPP exposure. CONCLUSIONS: Our findings reveal a truly antihypoxic mechanism for ITPP and demonstrate the capacity of this nontoxic compound to potentiate the efficacy of existing anticancer treatment in a way amenable to clinical translation. Clin Cancer Res; 22(23); 5887-97

Risk assessment in high- and low-MELD liver transplantation

Allocation of liver grafts triggers emotional debates, as those patients, not receiving an organ, are prone to death. We analyzed a high-Model of End-stage Liver Disease (MELD) cohort (laboratory MELD score ≥30, n = 100, median laboratory MELD score of 35; interquartile range 31-37) of liver transplant recipients at our center during the past 10 years and compared results with a low-MELD group, matched by propensity scoring for donor age, recipient age, and cold ischemia time. End points of our study were cumulative posttransplantation morbidity, cost, and survival. Six different prediction models, including donor age x recipient MELD (D-MELD), Difference between listing MELD and MELD at transplant (Delta MELD), donor-risk index (DRI), Survival Outcomes Following Liver Transplant (SOFT), balance-of-risk (BAR), and University of California Los Angeles-Futility Risk Score (UCLA-FRS), were applied in both cohorts to identify risk for poor outcome and high cost. All score models were compared with a clinical-oriented decision, based on the combination of hemofiltration plus ventilation. Median intensive care unit and hospital stays were 8 and 26 days, respectively, after liver transplantation of high-MELD patients, with a significantly increased morbidity compared with low-MELD patients (median comprehensive complication index 56 vs. 36 points [maximum points 100] and double cost [median US$179 631 vs. US$80 229]). Five-year survival, however, was only 8% less than that of low-MELD patients (70% vs. 78%). Most prediction scores showed disappointing low positive predictive values for posttransplantation mortality, such as mortality above thresholds, despite good specificity. The clinical observation of hemofiltration plus ventilation in high-MELD patients was even superior in this respect compared with D-MELD, DRI, Delta MELD, and UCLA-FRS but inferior to SOFT and BAR models. Of all models tested, only the BAR score was linearly associated with complications. In conclusion, the BAR score was most useful for risk classification in liver transplantation, based on expected posttransplantation mortality and morbidity. Difficult decisions to accept liver grafts in high-risk recipients may thus be guided by additional BAR score calculation, to increase the safe use of scarce organs