Anthony Gill

University of Sydney, Sydney, New South Wales, Australia

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Publications (82)416.07 Total impact

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    ABSTRACT: Purpose: PI3K/Akt is over-expressed in 50-70% of pancreatic ductal adenocarcinoma (PDAC). The hypothesis of this study is that PI3K and EGFR co-inhibition may be effective in PDAC with upregulated PI3K/Akt signaling. Experimental Design:Multiple inhibitors were tested on five PDAC cell lines. EGFR inhibitor (EGFRi) resistant cell lines significantly over-expressed AKT2 gene, total Akt and pAkt. In vitro erlotinib-resistant cell models (BxPC-ER, PANC-ER) with highly constitutively active PI3K/Akt were developed. These and their respective parent cell lines were tested for sensitivity to erlotinib, IGF1R inhibitor NVP-AEW541 (AEW), and PI3K-alpha inhibitor NVP-BYL719 (BYL), alone or in combination, by RTK-phosphoarray, western blotting, immunofluorescence, qRT-PCR, cell proliferation, cell cycle, clonogenic, apoptosis, and migration assays. Erlotinib plus BYL was tested in-vivo. Results:Multiple inhibitors were tested on five PDAC cell lines. EGFR inhibitor (EGFRi) resistant cell lines were found to have significantly over-expressed AKT2 gene, total Akt and pAkt. In vitro erlotinib-resistant cell models (BxPC-ER, PANC-ER) with highly constitutively active PI3K/Akt were developed. These and their respective parent cell lines were tested for sensitivity to erlotinib, IGF1R inhibitor NVP-AEW541 (AEW), and PI3K-alpha inhibitor NVP-BYL719 (BYL), alone or in combination, by RTK-phosphoarray, western blotting, immunofluorescence, qRT-PCR, cell proliferation, cell cycle, clonogenic, apoptosis, and migration assays. Erlotinib plus BYL was tested in-vivo. Conclusions:PDAC with increased expression of the PI3K/Akt pathway were susceptible to PI3K/ EGFR co-inhibition suggesting oncogenic dependence. Erlotinib plus BYL should be considered for a clinical study in PDAC; further evaluation of pEGFR and pAkt expression as potential positive and negative predictive biomarkers is warranted.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2014;
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    ABSTRACT: MiR-210 is a key regulator of response to hypoxia. Pheochromocytomas (PCs) and paragangliomas (PGLs) with germline SDHx or VHL mutations have pseudohypoxic gene expression signatures. We hypothesized that PC/PGLs containing SDHx or VHL mutations, and SDH-deficient gastrointestinal stromal tumours (GISTs), would overexpress miR-210 relative to non-SDH or -VHL-mutated counterparts. MiR-210 was analysed by quantitative PCR in: (a) 39 PC/PGLs, according to genotype (1 SDHA, 5 SDHB, 7 VHL, 3 NF1, 7 RET, 15 sporadic, 1 unknown) and pathology (18 benign, 8 atypical, 11 malignant, 2 unknown); (b) 18 gastrointestinal stromal tumours, according to SDHB immunoreactivity (9 SDH-deficient and 9 SDH-proficient); and (c) two novel SDHB-mutant neurosphere cell lines. MiR-210 was higher in SDHx- or VHL-mutated PC/PGLs (7.6 fold) compared to tumours without SDHx or VHL mutations (p=0.0016). MiR-210 was higher in malignant than in unequivocally benign PC/PGLs (p=0.05) but significance was lost when benign and atypical tumours were combined (p=0.08). In multivariate analysis, elevated miR-210 was significantly associated with SDHx or VHL mutation, but not with malignancy. In GISTs, miR-210 was higher in SDH-deficient (median 2.58) compared to SDH-proficient tumours (median 0.60; p=0.0078). MiR-210 was higher in patient-derived neurosphere cell lines containing SDHB mutations (6.5-fold increase) compared to normal controls, in normoxic conditions (p<.01). Furthermore, siRNA-knockdown of SDHB in HEK293 cells increased miR-210 by 2.7-fold (p = 0.001) under normoxia. Overall, our results suggest that SDH deficiency in PC, PGL and GISTs induces miR-210 expression and substantiates the role of aberrant hypoxic-type cellular responses in the development of these tumours.
    Endocrine Related Cancer 03/2014; · 5.26 Impact Factor
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    ABSTRACT: Although pancreatoduodenectomy (PD) with mesenterico-portal vein resection (VR) can be performed safely in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the impact of this approach on long-term survival is controversial. Analyses of a prospectively collected database revealed 122 consecutive patients with PDAC who underwent PD with (PD+VR) or without (PD-VR) VR between January 2004 and May 2012. Clinical data, operative results, and survival outcomes were analysed. Sixty-four (53 %) patients underwent PD+VR. The majority (84 %) of the venous reconstructions were performed with a primary end-to-end anastomosis. Demographic and postoperative outcomes were similar between the two groups. American Society of Anesthesiologists (ASA) score, duration of operation, intraoperative blood loss, and blood transfusion requirement were significantly greater in the PD+VR group compared with the PD-VR group. Furthermore, the tumor size was larger, and the rates of periuncinate neural invasion and positive resection margin were higher in the PD+VR group compared with the PD-VR group. Histological venous involvement occurred in 47 of 62 (76 %) patients in the PD+VR group. At a median follow-up of 29 months, the median overall survival (OS) was 18 months for the PD+VR group, and 31 months for the PD-VR group (p = 0.016). ASA score, lymph node metastasis, neurovascular invasion, and tumor differentiation were predictive of survival. The need for VR in itself was not prognostic of survival. PD with VR has similar morbidity but worse OS compared with a PD-VR. Although VR is not predictive of survival, tumors requiring a PD+VR have more adverse biological features.
    Annals of Surgical Oncology 02/2014; · 4.12 Impact Factor
  • European heart journal cardiovascular Imaging. 02/2014;
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    ABSTRACT: Accurate clinical and pathological data underpins all translational cancer research. Although synoptic reporting has largely replaced free text reporting for the assessment of most major cancer types, much of the historical pathological resources of research institutions were reported in free text format.We sought to assess the accuracy of data mining by relatively unskilled assessors (first year medical students) based on free text reports when compared to less skilled assessors (administrative assistance) based on synoptic reports.Four first year medical students were given formal instruction in the TNM staging system and printed material outlining the 7th edition 2009 AJCC staging system. They were asked to extract basic pathological data from all colon cancers resected over an 18 month period at our institution (group 1). As a control group, administrative assistants without formal training were asked to extract the same data from a consecutive 18 month cohort (group 2).In group 1 there were 417 cases, whereas there were 337 cases in group 2. There were similar numbers of stage py0 (1.9% vs 0%), stage 1 (15.2% vs 15.7%), stage 2A (21.3% vs 24.1%) stage 2C (0.7% to 0.2%), stage 3A (8.2% vs 2.3%), stage 3C (11% vs 11%) and stage 4A (3.5% vs 1.2%). In contrast the number of cases of p3B disease were markedly different between the two cohorts (33.3% compared to 17.3%).We are currently investigating the reason for this discrepancy, but we suspect this is due to incorrect classification of pN1C disease due to the difficulty of those without formal pathology training distinguishing extramural tumour nodules from other findings in the report. In conclusion, quality control processes are vital to ensure correct pathology data is mined from reports.
    Pathology 02/2014; 46 Suppl 1:S113. · 2.66 Impact Factor
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    ABSTRACT: Background Laparoscopic sleeve gastrectomy (SG) is gaining popularity as a revision option following failed laparoscopic adjustable gastric banding (LAGB). Data have shown that single stage revisions may be associated with a higher complication rate. A histological basis for this observation has not been studied. Objectives Document the histological properties of the LAGB capsule across the gastric staple line following SG at various time points after LAGB removal. Setting St George Private Hospital – Sydney, Australia. Royal North Shore Hospital – Sydney, Australia Methods Gastric sleeve specimens of all LAGB to SG revisions were identified from January to May 2013 and underwent histological evaluation of the LAGB capsule. Single blinded pathologist interpretation was performed, with inflammation, fibrosis, neovascularisation, foreign body (FB) reaction and wall thickness assessed semi-quantitatively and scored from 0-3. Based on combined features, an attempt was made to predict the timing of revision surgery. Results The study identified 19 revisions performed for inadequate excess body weight loss or weight regain. The mean age for revision was 44 (19-65). The minimum time to revision was 42 days, the longest 1,188 days. There were no surgical complications. Varying degrees of inflammation and fibrosis were common features at all time periods. Angiogenesis, neovascularisation and FB reaction were prominent in revisions performed before 80 days. The gastric wall was thicker during early revision. The optimal time to perform revision was difficult to determine. Conclusions LAGB caused varying degrees of inflammatory and FB reaction that time did not fully resolve. The lower leak rates observed with delayed revisions do not appear to be attributable to gastric histology.
    Surgery for Obesity and Related Diseases 01/2014; · 4.12 Impact Factor
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    ABSTRACT: This study aimed to investigate whether maternal cigarette smoke exposure can disrupt fetal kidney development by changing the expression of growth and transcription factors essential for renal development, and thereafter predispose the offspring to chronic kidney disease later in life. Female Balb/c mice (6 weeks) were exposed either to cigarette smoke or air under identical conditions, 6 weeks prior to mating, during gestation and during lactation. Male offspring were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and 13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At P1, the developmental genes fibroblast growth factor 2, glial cell-line derived neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels; whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20, mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal smoke exposure. These changes were normalised in adulthood. Nephron development was delayed, with fewer nephron numbers from P1 persisted to adulthood; while glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by maternal smoke exposure. These changes were accompanied by an increased albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In conclusion maternal cigarette smoke exposure prior to and during pregnancy, as well as lactation leads to significant renal underdevelopment and functional abnormalities in adulthood. This study confirms the hypothesis that maternal smoking predisposes offspring to chronic kidney disorders.
    PLoS ONE 01/2014; 9(7):e103443. · 3.53 Impact Factor
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    ABSTRACT: Papillary thyroid cancer (PTC) persistence or recurrence and the need for long-term surveillance can cause significant inconvenience and morbidity in patients. Currently, recurrence risk stratification is accomplished by using clinicopathologic factors, and serum thyroglobulin is the only commercially available marker for persistent or recurrent disease. The objective of this study was to determine microRNA (miRNA) expression in PTC and determine whether 1 or more miRNAs could be measured in plasma as a biomarker for recurrence. Patients with recurrent PTC (Rc-PTC) and those without recurrence (NR-PTC) were retrospectively recruited for a comparison of their tumor miRNA profiles. Patients with either newly diagnosed PTC or multinodular goiter who were undergoing total thyroidectomy were prospectively recruited for an analysis of preoperative and postoperative circulating miRNA levels. Healthy volunteers were recruited as the control group. MicroRNA-222 and miR-146b were over-expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR-PTC tumors (P = .014 and P = .038, respectively). In plasma from preoperative PTC patients, levels of miR-222 and miR-146b were higher compared with the levels in plasma from healthy volunteers (P < .01 for both). Reductions of 2.7-fold and 5.1-fold were observed in the plasma levels of miR-222 and miR-146b, respectively, after total thyroidectomy (P = .03 for both). This study demonstrated that tumor levels of miR-222 and miR-146b are associated with PTC recurrence and that miR-222 and miR-146b levels in the circulation correspond to the presence of PTC. The potential of these miRNAs as tumor biomarkers to improve patient stratification according to the risk of recurrence and as circulating biomarkers for PTC surveillance warrants further study. Cancer 2013;119:4358-4365. © 2013 American Cancer Society.
    Cancer 12/2013; 119(24):4358-65. · 5.20 Impact Factor
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    ABSTRACT: BACKGROUND: Papillary thyroid cancer (PTC) persistence or recurrence and the need for long-term surveillance can cause sig-nificant inconvenience and morbidity in patients. Currently, recurrence risk stratification is accomplished by using clinicopatho-logic factors, and serum thyroglobulin is the only commercially available marker for persistent or recurrent disease. The objective of this study was to determine microRNA (miRNA) expression in PTC and determine whether 1 or more miRNAs could be measured in plasma as a biomarker for recurrence. METHODS: Patients with recurrent PTC (Rc-PTC) and those without recur-rence (NR-PTC) were retrospectively recruited for a comparison of their tumor miRNA profiles. Patients with either newly diagnosed PTC or multinodular goiter who were undergoing total thyroidectomy were prospectively recruited for an analysis of preoperative and postoperative circulating miRNA levels. Healthy volunteers were recruited as the control group. RESULTS: MicroRNA-222 and miR-146b were over-expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR-PTC tumors (P 5.014 and P 5.038, respectively). In plasma from preoperative PTC patients, levels of miR-222 and miR-146b were higher compared with the lev-els in plasma from healthy volunteers (P <.01 for both). Reductions of 2.7-fold and 5.1-fold were observed in the plasma levels of miR-222 and miR-146b, respectively, after total thyroidectomy (P 5.03 for both). CONCLUSIONS: This study demonstrated that tumor lev-els of miR-222 and miR-146b are associated with PTC recurrence and that miR-222 and miR-146b levels in the circulation correspond to the presence of PTC. The potential of these miRNAs as tumor biomarkers to improve patient stratification according to the risk of recurrence and as circulating biomarkers for PTC surveillance warrants further study. Cancer 2013;000:000-000. V C 2013 American Cancer Society.
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    ABSTRACT: Early inferior pancreaticoduodenal artery (IPDA) ligation reduces intraoperative blood loss during pancreatoduodenectomy, but the impact on oncologic and long-term outcomes remains unknown. The aim of this study was to review the impact of complete pancreatic head devascularization during pancreatoduodenectomy on blood loss, transfusion rates, and clinicopathologic outcomes. Clinicopathologic and outcome data were retrieved from a prospective database for all pancreatoduodenectomies performed from April 2004 to November 2010 and compared between early (IPDA+; n = 62) and late (IPDA-; n = 65) IPDA ligation groups. Early IPDA ligation was associated with reduced blood loss (394 ± 21 vs 679 ± 24 ml, P < .001) and perioperative transfusion (P = .031). A trend toward improved R0 resection was seen in patients with pancreatic adenocarcinoma (IPDA+ vs IPDA-, 100% vs 82%; P = .059), but this did not translate to improved 2-year (IPDA+ vs IPDA-, 76% vs 65%; P = .426) or overall (P = .82) survival. Early IPDA ligation reduces blood loss and transfusion requirements. Despite overall survival being unchanged, a trend toward improved R0 resection is encouraging and justifies further studies to ascertain the true oncologic significance of this technique.
    American journal of surgery 06/2013; · 2.36 Impact Factor
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    ABSTRACT: AIM: We assessed the diagnostic accuracy of epidermal growth factor receptor (EGFR) mutant-specific antibodies for detecting two common activating EGFR mutations. METHODS: Immunohistochemical expression of mutation-specific antibodies against EGFR exon 19 deletion E746-A750 ((c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg) were assessed in a cohort of 204 resected early stage node negative lung adenocarcinomas, and protein expression was compared with DNA analysis results from mass spectrometry analysis. RESULTS: Of seven cases with L858R point mutation, six were positive by immunohistochemistry (IHC). There were three false positive cases using L858R IHC (sensitivity 85.7%, specificity 98.5%, positive predictive value 66.7%, negative predictive value 99.5%). All seven E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. Four additional cases were positive for exon 19 IHC but negative by mutation analysis. The sensitivity of exon 19 IHC for E746-A750 was 100%, specificity 98.0%, positive predictive value 63.6% and negative predictive value 100%. CONCLUSIONS: Mutant-specific EGFR IHC has good specificity and sensitivity for identifying targeted activating EGFR mutations. Although inferior to molecular genetic analysis of the EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations. The antibodies are likely to be of clinical value in cases where limited tumour material is available, or in situations where molecular genetic analysis is not readily available.
    Journal of clinical pathology 06/2013; · 2.43 Impact Factor
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    ABSTRACT: While colorectal cancer is increasingly common in western populations, anatomical concepts regarding the anatomy of resection have remained static. In attempting to maximise the chance of surgical cure, surgeons and pathologists are now focussing upon the quality of oncological resection. Amongst pathological indices of interest, lymph node yield and the apical lymph node specifically are increasingly being shown to be reliable markers of the adequacy of oncologic resection. However, the position of the apical node in particular, is highly subjective and may not always correlate with the anatomical boundaries ultimately defining resection. We argue that the present definition of the apical lymph node is overly subjective and requires re-defining based on fixed anatomical landmarks. We propose that this new definition include a block of tissue inferolateral to the Trunk of Henle (the anatomical apical lymph node compartment).
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 03/2013; · 2.56 Impact Factor
  • Anthony J Gill
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    ABSTRACT: So the Scottish poet Robert Burns drew an analogy between the suffering of a field mouse whose nest has been overturned by a plough to the unexpected way in which human life can be disrupted by events beyond our control. Burns is saying that mice and humans facing unforseen catastrophes such as cancer have much in common. Unfortunately, whilst it is clear that there are some similarities between mouse models of cancer and cancer as seen in the clinic, the artificial conditions presented by animal models are very different to those found in humans with cancer. It cannot be assumed that even basic pathophysiologic processes found in animal models are anything more than a model (literally a 'likeness') of similar processes found in the clinic. With these caveats, Barone et al's paper published in this edition of Colorectal Disease (REF1) provides important insights into the pathophysiology of cytokeratin positive cells in the bone marrow of patients with colorectal cancer. © 2013 The Authors. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
    Colorectal Disease 03/2013; · 2.08 Impact Factor
  • European Heart Journal 03/2013; · 14.10 Impact Factor
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    ABSTRACT: PURPOSEIndividuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. PATIENTS AND METHODS We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. RESULTS: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. CONCLUSION Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.
    Journal of Clinical Oncology 02/2013; · 18.04 Impact Factor
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    ABSTRACT: BACKGROUND: Therapeutic central neck dissection (CND) is an accepted part of the management of papillary thyroid carcinoma (PTC), while prophylactic CND remains controversial. Regardless of the indication for CND, the lower anatomic border of the central compartment, specifically the inclusion or otherwise of level VII, is not always clearly defined in the literature. This study aimed to determine if the routine inclusion of level VII lymph node dissection as part of CND confers increased utility in the detection of macrometastatic lymph nodes compared with level VI dissection alone. METHOD: This was a prospective cohort study of patients undergoing CND for PTC at a tertiary referral center. All patients received either a prophylactic or therapeutic CND. The CND specimens were divided by the surgeon into level VI and level VII at the level of the suprasternal notch and submitted separately for histopathology. Criteria for macroscopic lymph node disease were taken from the American Joint Committee on Cancer (AJCC) recommendations for breast cancer. RESULTS: A total of 45 patients with PTC underwent total thyroidectomy and routine CND, at a tertiary referral center; 77 % of the therapeutic CND group had positive level VI lymph nodes, and 38 % had positive level VII lymph nodes. Of the prophylactic CND group, 50 % of patients had positive level VI nodes and 16 % has positive level VII nodes detected. All patients with positive level VII lymph nodes in the prophylactic CND group had macrometastatic disease. Temporary hypocalcemia rate was 31 % in the therapeutic group and 6 % in the prophylactic CND group. One patient experienced permanent hypoparathyroidism. There was no vascular injury or recurrent laryngeal nerve palsy in either group. CONCLUSIONS: CND incorporating both level VI and level VII can be undertaken safely through a cervical incision with no increased risk of permanent complications of hypoparathyroidism or recurrent laryngeal nerve injury. Failure to include level VII as part of CND will leave significant macrometastatic nodal disease behind in both therapeutic and prophylactic dissections. As level VII is in direct anatomic continuity with the pretracheal level VI nodes, it should be routinely included as part of every CND.
    Annals of Surgical Oncology 01/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: Cardiac involvement in sarcoidosis is associated with a poor prognosis. In patients with right sided heart failure, differentiating between cor-pulmonale, or cardiac sarcoidosis has important implications to management. CASE PRESENTATION: We present the case of a patient with severe but stable pulmonary sarcoidosis and new onset right sided heart failure despite only mild elevations of pulmonary artery pressure. CMR demonstration of extensive right ventricular fibrosis with associated dilatation and hypokinesis was a key finding for prognosis and management of the patient. CONCLUSION: Cardiac magnetic resonance (CMR) is the preferred investigation in the diagnosis of cardiac sarcoidosis, allowing assessment of myocardial inflammation and fibrosis, as well as function, in a manner not matched by other technologies.
    BMC Medical Imaging 01/2013; 13(1):2. · 1.09 Impact Factor
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    ABSTRACT: Context:Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging.Objective:We studied the utility of (68)Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO.Design and Setting:A multicenter case series was conducted at tertiary referral hospitals.Patients and Methods:Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient.Results:Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry.Conclusions:In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO.
    The Journal of clinical endocrinology and metabolism 01/2013; · 6.50 Impact Factor
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    ABSTRACT: Background:Pancreaticoduodenectomy remains a major undertaking. A preoperative blood test, which could confidently predict the benefits of surgery would improve the selection of pancreatic cancer patients for surgery. This study aimed to identify protein biomarkers prognostic for long-term survival and to validate them with clinico-pathological information.Methods:Serum from 40 preoperative patients was used to train for predictive biomarkers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI), and the results were verified on 21 independent samples. Two predictive proteins were identified by tryptic peptide mass fingerprinting and sequencing, and validated on serum from another 57 patients by enzyme-linked immunosorbent assay (ELISA). The influence of these proteins on growth and invasion of two cancer cell lines was tested in-vitro.Results:The SELDI panel of m/z 3700, 8222 and 11 522 peaks predicted <12 months' survival (ROC AUC: 0.79, 0.64-0.90; P<0.039). When CA19-9 was added, the ROC AUC increased to 0.95 (0.84-0.99; P<0.0001). The six subjects in the verification group who died within 12 months were correctly classified. The m/z 8222 and 11 522 proteins were identified as Serum ApoC-II and SAA-1, respectively. In the validation samples, ELISA results confirmed that ApoC-II was predictive of survival (Kaplan-Meier P<0.009), but not SAA-I. ApoC-II, CA19-9 and major-vessel involvement independently predicted survival. ApoC-II and SAA-1 increased cell growth and invasion of both cancer cell lines.Conclusion:Serum ApoC-II, CA19-9 and major-vessel invasion independently predict survival and improves selection of patients for pancreaticoduodenectomy.
    British Journal of Cancer 11/2012; 107(11):1883-91. · 5.08 Impact Factor

Publication Stats

730 Citations
416.07 Total Impact Points

Institutions

  • 2007–2014
    • University of Sydney
      • School of Molecular Bioscience
      Sydney, New South Wales, Australia
  • 2005–2014
    • Royal North Shore Hospital
      Sydney, New South Wales, Australia
  • 2007–2013
    • Kolling Institute of Medical Research
      Sydney, New South Wales, Australia