Publications by authors named "Anthony Longano"

30 Publications

  • Page 1 of 1

Phlegmonous gastritis: an unusual mimic of gastric cancer.

ANZ J Surg 2021 Jan 15. Epub 2021 Jan 15.

Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.16580DOI Listing
January 2021

Concurrent anti-GBM disease and IgA glomerulonephritis.

Authors:
Anthony Longano

Pathology 2019 Apr 2;51(3):336-338. Epub 2019 Mar 2.

Department of Anatomical Pathology, Eastern Health, Box Hill Hospital, Box Hill, Vic, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.pathol.2018.09.065DOI Listing
April 2019

Activation of ERBB4 in Glioblastoma Can Contribute to Increased Tumorigenicity and Influence Therapeutic Response.

Cancers (Basel) 2018 Jul 25;10(8). Epub 2018 Jul 25.

Oncogenic Signalling Group, Hudson Institute of Medical Research, 21⁻37 Wright Street, Clayton, VIC 3168, Australia.

Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ErbB2 Receptor Tyrosine Kinase 4 (ERBB4) is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total mRNA was significantly lower in GBM than NNB samples, with the juxtamembrane JM-a and cytoplasmic CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0 ± 3.2 months) than was no p-ERBB4 (22.5 ± 9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.
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http://dx.doi.org/10.3390/cancers10080243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116191PMC
July 2018

Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates with injury in antineutrophil cytoplasmic antibody-associated vasculitis.

Am J Physiol Renal Physiol 2018 11 20;315(5):F1283-F1294. Epub 2018 Jun 20.

Centre for Inflammatory Diseases, Monash University Department of Medicine , Clayton, Victoria , Australia.

In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like receptors (TLRs) may be engaged by infection-associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression and the intensity of glomerular TLR2 expression inversely correlated with the presenting estimated glomerular filtration rate. Although myeloid cells within the kidney expressed TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the colocalization of TLRs with their endogenous ligands high-mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.
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http://dx.doi.org/10.1152/ajprenal.00040.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293285PMC
November 2018

Dietary intake of nutrients involved in one-carbon metabolism and risk of urothelial cell carcinoma: A prospective cohort study.

Int J Cancer 2018 07 1;143(2):298-306. Epub 2018 Mar 1.

Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.

Nutrients involved in one-carbon metabolism may play a role in carcinogenesis through DNA replication, repair and methylation mechanisms. Most studies on urothelial cell carcinoma (UCC) have focused on folate. We sought to examine the association between B-group vitamins and methionine intake and UCC risk, overall and by subtype, and to test whether these associations are different for population subgroups whose nutritional status may be compromised. We followed participants in the Melbourne Collaborative Cohort Study (N = 41,513) for over 20 years and observed 500 UCC cases (89% originating in the bladder; superficial: 279, invasive: 221). Energy-adjusted dietary intakes of B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12) and methionine were estimated from a 121-item food frequency questionnaire administered at baseline (1990-1994), using the residuals method. We used Cox regression models to compute hazard ratios (HRs) of UCC risk per standard deviation (SD) of log-transformed nutrient intakes and 95% confidence intervals, adjusted for potential confounders. We investigated associations by tumor subtype, and tested interactions with sex, country of birth, smoking and alcohol drinking. The risk of UCC appeared not to be associated with intake of B-group vitamins or methionine, and findings were consistent across tumor subtypes and across demographic and lifestyle characteristics of the participants. A potential interaction between vitamin B1 and alcohol drinking was observed (all participants: HR per 1 SD = 0.99 (0.91-1.09), never drinkers: HR = 0.81 (0.69-0.97), p-interaction = 0.02), which needs to be confirmed by other studies. Our findings do not indicate that dietary intake of nutrients involved in one-carbon metabolism are associated with UCC risk.
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http://dx.doi.org/10.1002/ijc.31319DOI Listing
July 2018

Long-term graft survival in patients with chronic antibody-mediated rejection with persistent peritubular capillaritis treated with intravenous immunoglobulin and rituximab.

Clin Transplant 2017 Sep 13;31(9). Epub 2017 Jul 13.

Department of Nephrology, Monash Medical Centre, Clayton, Vic., Australia.

Chronic antibody-mediated rejection (cAMR) is the major cause of premature renal allograft loss and is resistant to therapy with 12-month graft failure of up to 50% reported. We examined the duration of graft survival and associates of graft failure in patients with donor-specific antibody-positive cAMR and treatment-resistant peritubular capillaritis between June 2007 and October 2010. Those with advanced interstitial fibrosis (n=5) were excluded. Included patients (n=24) received treatment with high-dose intravenous immunoglobulin and fixed-dose rituximab (500 mg). Compared with previous reports, the study group experienced prolonged graft survival (median 82.1 months). Graft loss was predicted by eGFR and degree of proteinuria at diagnosis but not by donor-specific HLA antibody class or intensity, nor individual or summed Banff scores. Allograft biopsies were further examined for infiltrating leukocyte subtypes and location with high numbers of glomerular leukocytes, particularly macrophages, independently associated with an increased risk of graft failure. This study suggests that patients with cAMR and persistent microcirculatory inflammation, excluding those with advanced histological damage, can expect prolonged graft survival when treated with IVIg and rituximab. Trial level evidence is required to validate this observation. Further examination of the role of macrophages in cAMR is warranted.
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http://dx.doi.org/10.1111/ctr.13037DOI Listing
September 2017

Cranial Pilocytic Astrocytoma With Spinal Drop Metastasis in an Adult: Case Report and Literature Review.

World Neurosurg 2017 Feb 12;98:883.e7-883.e12. Epub 2016 Aug 12.

Department of Neurosurgery, Monash Medical Centre, Melbourne, Australia; Department of Surgery and Monash Institute of Medical Research, Monash University, Melbourne, Australia.

Background: Pilocytic astrocytoma (PA) is a benign neoplasm that typically occurs in the brain within the pediatric and adolescent age groups and is uncommon in adults. It rarely occurs within the ventricles, and the overall prognosis is favorable. A PA of the brain with spinal metastasis at presentation has never been reported in an adult.

Case Description: We report a case of a 47-year-old man presenting with sudden-onset frontal headache associated with nausea and lethargy in addition to a background of a longer history of back pain and headache. Radiologic imaging revealed an acute intraparenchymal hemorrhage in the right parieto-occipital lobes with intraventricular extension within a peripherally enhancing heterogeneous lesion. Magnetic resonance imaging of the spine revealed a sacral intradural tumor. The patient underwent surgical resection of the intracranial mass followed by debulking of the spinal lesion. Histopathologic study revealed that both the cranial and spinal tumors were PA.

Conclusions: This case illustrates a unique instance of hemorrhage into a cerebral PA with a spinal metastasis. To our knowledge, this is the first such case reported in an adult. We review the literature on the subject.
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http://dx.doi.org/10.1016/j.wneu.2016.08.013DOI Listing
February 2017

Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case-control study.

Br J Cancer 2016 09 4;115(6):664-73. Epub 2016 Aug 4.

Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.

Background: Global DNA methylation has been reported to be associated with urothelial cell carcinoma (UCC) by studies using blood samples collected at diagnosis. Using the Illumina HumanMethylation450 assay, we derived genome-wide measures of blood DNA methylation and assessed them for their prospective association with UCC risk.

Methods: We used 439 case-control pairs from the Melbourne Collaborative Cohort Study matched on age, sex, country of birth, DNA sample type, and collection period. Conditional logistic regression was used to compute odds ratios (OR) of UCC risk per s.d. of each genome-wide measure of DNA methylation and 95% confidence intervals (CIs), adjusted for potential confounders. We also investigated associations by disease subtype, sex, smoking, and time since blood collection.

Results: The risk of superficial UCC was decreased for individuals with higher levels of our genome-wide DNA methylation measure (OR=0.71, 95% CI: 0.54-0.94; P=0.02). This association was particularly strong for current smokers at sample collection (OR=0.47, 95% CI: 0.27-0.83). Intermediate levels of our genome-wide measure were associated with decreased risk of invasive UCC. Some variation was observed between UCC subtypes and the location and regulatory function of the CpGs included in the genome-wide measures of methylation.

Conclusions: Higher levels of our genome-wide DNA methylation measure were associated with decreased risk of superficial UCC and intermediate levels were associated with reduced risk of invasive disease. These findings require replication by other prospective studies.
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http://dx.doi.org/10.1038/bjc.2016.237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023776PMC
September 2016

Inflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report.

Urol Case Rep 2016 May 5;6:58-9. Epub 2016 Apr 5.

Department of Urology, Monash Health, Bentleigh East, VIC, Australia.

Inflammatory myofibroblastic tumor is a rare but benign clinical entity. Its ability to mimic malignancy poses a diagnostic challenge. Here, we report the first case in Australia, of inflammatory myofibroblastic tumor in the bladder in a 40-year-old male, removed via transurethral resection.
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http://dx.doi.org/10.1016/j.eucr.2016.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855986PMC
May 2016

Surgical margins in head and neck squamous cell carcinoma: Effect of heat artifact on immunohistochemistry as a future tool for assessment.

Head Neck 2016 09 4;38(9):1401-6. Epub 2016 Apr 4.

Hudson Institute of Medical Research, Melbourne, Victoria, Australia.

Background: Margins in head and neck squamous cell carcinoma (HNSCC) are determined by morphological changes assessed via hematoxylin-eosin staining. Physiological changes may not be detected by this technique. The purpose of this study was to determine if a protein biomarker, laminin-332γ2, overexpressed in cancer cells at the invasive front in HNSCC, remains unaffected by heat produced during resection, supporting a role for immunohistochemistry assessment of margins.

Methods: Archived tissue blocks from glottic squamous cell carcinomas (SCCs) resected by CO2 laser likely to contain both cancer cells and artifact were identified; 129-paired slides were obtained. One slide of each pair was stained with hematoxylin-eosin; the second stained for laminin-332γ2. The presence of cancer cells, artifact, and positive laminin-332γ2 staining was recorded. Twenty-seven pairs met the inclusion criteria.

Results: Immunohistochemistry staining of laminin-332γ is preserved in presence of heat artifact.

Conclusion: This study supports use of immunohistochemistry to assess margins. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1401-1406, 2016.
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http://dx.doi.org/10.1002/hed.24450DOI Listing
September 2016

Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis.

Kidney Int 2015 Nov 15;88(5):1030-46. Epub 2015 Jul 15.

Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.

Myeloperoxidase (MPO) is an important neutrophil lysosomal enzyme, a major autoantigen, and a potential mediator of tissue injury in MPO-ANCA-associated vasculitis (MPO-AAV) and glomerulonephritis. Here we examined MPO deposition in kidney biopsies from 47 patients with MPO-AAV. Leukocyte accumulation and fibrin deposition consistent with cell-mediated immunity was a major feature. Tubulointerstitial macrophage, CD4+ and CD8+ T-cell, and neutrophil numbers correlated with low presenting eGFR. MPO was not detected in kidneys from patients with minimal change or thin basement membrane disease, but was prominent in glomerular, periglomerular, and tubulointerstitial regions in MPO-AAV. Extracellular MPO released from leukocytes was pronounced in all MPO-AAV patients. Similar numbers of neutrophils and macrophages expressed MPO in the kidneys, but colocalization studies identified neutrophils as the major source of extracellular MPO. Extraleukocyte MPO was prominent in neutrophil extracellular traps in the majority of patients; most of which had traps in half or more glomeruli. These traps were associated with more neutrophils and more MPO within glomeruli. Glomerular MPO-containing macrophages generated extracellular trap-like structures. MPO also localized to endothelial cells and podocytes. The presence of the most active glomerular lesions (both segmental necrosis and cellular crescents) correlated with intraglomerular CD4+ cells and MPO+ macrophages. Thus, cellular and extracellular MPO may cause glomerular and interstitial injury.
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http://dx.doi.org/10.1038/ki.2015.202DOI Listing
November 2015

Detection of infectious organisms in archival prostate cancer tissues.

BMC Cancer 2014 Aug 9;14:579. Epub 2014 Aug 9.

Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.

Background: Seroepidemiological studies have reported associations between exposure to sexually transmitted organisms and prostate cancer risk. This study sought DNA evidence of candidate organisms in archival prostate cancer tissues with the aim of assessing if a subset of these cancers show any association with common genital infections.

Methods: 221 archival paraffin-embedded tissue blocks representing 128 histopathologically confirmed prostate cancers comprising 52 "aggressive" (Gleason score ≥ 7) and 76 "non-aggressive" (Gleason score ≤ 6) TURP or radical prostatectomy specimens were examined, as well as unaffected adjacent tissue when available. Representative tissue sections were subjected to DNA extraction, quality tested and screened by PCR for HSV-1, HSV-2, XMRV, BKV, HPV, Chlamydia trachomatis, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma genitalium, and Trichomonas vaginalis.

Results: 195 of 221 DNA samples representing 49 "aggressive" and 66 "non-aggressive" prostate cancer cases were suitable for analysis after DNA quality assessment. Overall, 12.2% (6/49) aggressive and 7.6% (5/66) non-aggressive cases were positive for any of the candidate organisms. Mycoplasma genitalium DNA was detected in 4/66 non-aggressive, 5/49 aggressive cancers and in one cancer-unaffected adjacent tissue block of an aggressive case. Ureaplasma urealyticum DNA was detected in 0/66 non-aggressive and 1/49 aggressive cancers and HSV DNA in 1/66 non-aggressive and 0/49 aggressive cancers. This study did not detect BKV, XMRV, T. vaginalis, U. parvum, C. trachomatis or HPV DNA.

Conclusions: The low prevalence of detectable microbial DNA makes it unlikely that persistent infection by the selected candidate microorganisms contribute to prostate cancer risk, regardless of tumour phenotype.
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http://dx.doi.org/10.1186/1471-2407-14-579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132904PMC
August 2014

Cervical Langerhans cell histiocytosis (histiocytosis X).

ANZ J Surg 2016 Dec 31;86(12):1056-1057. Epub 2014 Jul 31.

Department of Ear, Nose & Throat/Head & Neck Surgery, Monash Medical Centre, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.12794DOI Listing
December 2016

A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease.

Cancer Med 2014 Oct 7;3(5):1266-74. Epub 2014 Jun 7.

Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, 3004, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Victoria, 3010, Australia.

Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, "cases" (N = 83), were matched to "referents" (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14-5.54, P = 0.02 and 3.08, 95% CI 1.41-6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20-0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.
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http://dx.doi.org/10.1002/cam4.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302676PMC
October 2014

p40 immunoperoxidase staining of anorectal carcinomas.

Histopathology 2015 Feb 18;66(3):464-6. Epub 2014 Dec 18.

Department of Anatomical Pathology, Monash Medical Centre, Clayton, Vic., Australia.

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http://dx.doi.org/10.1111/his.12470DOI Listing
February 2015

Primary dedifferentiated liposarcoma of the lung with rhabdomyoblastic and chrondroblastic differentiation.

Histopathology 2015 Dec 6;67(6):923-5. Epub 2014 Aug 6.

Department of Anatomical Pathology, Peter MacCallum Cancer Institute, East Melbourne, Vic., Australia.

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http://dx.doi.org/10.1111/his.12410DOI Listing
December 2015

IL-6/Stat3-driven pulmonary inflammation, but not emphysema, is dependent on interleukin-17A in mice.

Respirology 2014 Apr 10;19(3):419-27. Epub 2014 Feb 10.

Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.

Background And Objective: Pulmonary emphysema is linked to T cell-mediated autoimmune inflammation, although the pathogenic role of specific pro-inflammatory cytokines remains unclear. The Th17 type response, characterized by the production of the cytokine interleukin (IL)-17A, is modulated in part by the IL-6/signal transducer and activator of transcription (Stat)3 signalling axis and is associated with numerous autoimmune diseases. We therefore evaluated a causal role for IL-17A in the IL-6-driven gp130(F/F) mouse model for spontaneous pulmonary inflammation and emphysema.

Methods: The expression of Th17-related factors was quantified in the lungs of gp130(F/F) mice and emphysematous patients, and the degree of pulmonary inflammation and emphysema was measured in gp130(F/F)  : Il17a-/- mice by immunohistochemistry, stereology and respiratory mechanics.

Results: In gp130(F/F) mice, lung gene expression of Il17a and other Th17-related factors was augmented compared with gp130+/+ (wild-type), gp130(F/F)  : Il6-/- and gp130(F/F)  : Stat3-/+ mice displaying normalized Stat3 activity and no lung inflammation. Importantly, genetic ablation of Il17a in gp130(F/F)  : Il17a-/- mice prevented lung inflammation; however, emphysema still developed. Additionally, messenger RNA expression of inflammatory genes Cxcl1, Cxcl2, Ccl2 and Tnfα; as well as Il6 and the Stat3-target gene, Socs3, were upregulated in the lungs of gp130(F/F) mice compared with gp130(F/F)  : Il17a-/- and gp130+/+ mice. Consistent with these findings, augmented IL17A expression was observed in emphysema patients presenting with inflammation compared with inflammation-free individuals.

Conclusions: Collectively, our data suggest that the integration of IL-17A into the IL-6/Stat3 signalling axis mediates lung inflammation, but not emphysema, and that discrete targeting of IL-17A may alleviate pulmonary inflammatory-related diseases.
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http://dx.doi.org/10.1111/resp.12243DOI Listing
April 2014

Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis.

Am J Kidney Dis 2014 Feb 30;63(2):227-35. Epub 2013 Oct 30.

Center for Inflammatory Diseases, Department of Medicine, Monash Medical Center, Clayton, VIC, Australia; Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia. Electronic address:

Background: A predictive histologic classification recently was proposed to determine the prognostic value of kidney biopsy in patients with antineutrophil cytoplasmic antibody-associated renal vasculitis (AAV).

Study Design: A dual-purpose retrospective observational cohort study to assess the reproducibility of the new classification and clinical variables that predict outcomes.

Setting & Participants: 169 consecutive patients with AAV were identified; 145 were included in the reproducibility study, and 120, in the outcomes study.

Predictor: Kidney biopsy specimens were classified according to the predominant glomerular lesion: focal, mixed, crescentic, and sclerotic. An assessment of tubular atrophy also was performed.

Outcomes: The primary outcome was time to end-stage kidney disease or all-cause mortality, modeled using Cox regression analysis.

Measurements: Estimated glomerular filtration rate, requirement for renal replacement therapy.

Results: For the reproducibility study, the overall inter-rater reliability of the classification demonstrated variability among 3 histopathologists (intraclass correlation coefficient, 0.48; 95% CI, 0.38-0.57; κ statistic=0.46). Although agreement was high in the sclerotic group (κ=0.70), it was less consistent in other groups (κ=0.51, κ=0.47, and κ=0.23 for crescentic, focal, and mixed, respectively). For the clinical outcomes study, patients with sclerotic patterns of glomerular injury displayed the worst outcomes. Patients with focal (HR, 0.26; 95% CI, 0.12-0.58; P=0.001), crescentic (HR, 0.33; 95% CI, 0.16-0.69; P=0.003), and mixed (HR, 0.39; 95% CI, 0.18-0.81; P=0.01) patterns of injury had lower risk of the primary outcome. Tubular atrophy correlated with outcome, and advanced injury was associated with worse outcomes (HR, 5.9; 95% CI, 2.25-15.47; P<0.001). Level of kidney function at presentation strongly predicted outcome (HR per 10-mL/min/1.73m(2) increase in estimated glomerular filtration rate, 0.63; 95% CI, 0.46-0.81; P<0.001).

Limitations: Data availability, given the retrospective nature of the study.

Conclusions: Reproducibility of the classification was seen only in patients with sclerotic patterns of glomerular injury. Sclerotic pattern of glomerular injury, advanced chronic interstitial injury, and decreased kidney function all predicted poor outcomes.
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http://dx.doi.org/10.1053/j.ajkd.2013.08.025DOI Listing
February 2014

Lipoblastoma: an interesting differential of paediatric lipoma.

ANZ J Surg 2014 May 28;84(5):387-8. Epub 2013 Oct 28.

Ear, Nose and Throat Department, Southern Health, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.12238DOI Listing
May 2014

Deregulated Stat3 signaling dissociates pulmonary inflammation from emphysema in gp130 mutant mice.

Am J Physiol Lung Cell Mol Physiol 2012 Apr 20;302(7):L627-39. Epub 2012 Jan 20.

Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash Univ., Clayton, Victoria, Australia.

Interleukin (IL)-6 is a potent immunomodulatory cytokine that is associated with emphysema, a major component of chronic obstructive pulmonary disease (COPD). IL-6 signaling via the gp130 coreceptor is coupled to multiple signaling pathways, especially the latent transcription factor signal transducer and activator of transcription (Stat)3. However, the pathological role of endogenous gp130-dependent Stat3 activation in emphysema is ill defined. To elucidate the role of the IL-6/gp130/Stat3 signaling axis in the cellular and molecular pathogenesis of emphysema, we employed a genetic complementation strategy using emphysematous gp130(F/F) mice displaying hyperactivation of endogenous Stat3 that were interbred with mice to impede Stat3 activity. Resected human lung tissue from patients with COPD and COPD-free individuals was also evaluated by immunohistochemistry. Genetic reduction of Stat3 hyperactivity in gp130(F/F):Stat3(-/+) mice prevented lung inflammation and excessive protease activity; however, emphysema still developed. In support of these findings, Stat3 activation levels in human lung tissue correlated with the extent of pulmonary inflammation but not airflow obstruction in COPD. Furthermore, COPD lung tissue displayed increased levels of IL-6 and apoptotic alveolar cells, supporting our previous observation that increased endogenous IL-6 expression in the lungs of gp130(F/F) mice contributes to emphysema by promoting alveolar cell apoptosis. Collectively, our data suggest that IL-6 promotes emphysema via upregulation of Stat3-independent apoptosis, whereas IL-6 induction of lung inflammation occurs via Stat3. We propose that while discrete targeting of Stat3 may alleviate pulmonary inflammation, global targeting of IL-6 potentially represents a therapeutically advantageous approach to combat COPD phenotypes where emphysema predominates.
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http://dx.doi.org/10.1152/ajplung.00285.2011DOI Listing
April 2012

Cardiac metastasis from thyroid carcinoma.

Thyroid 2011 Aug 13;21(8):855-66. Epub 2011 Jul 13.

Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Australia.

Cardiac metastasis from epithelial thyroid cancer is a very rare and potentially serious complication. We have identified only 54 reported cases over a 130-year period. Here we review this literature. Cardiac metastases are frequently asymptomatic, but when symptoms develop these tend to be severe and often fatal. The prognosis of cardiac metastases from thyroid cancer is unclear as survival data are often missing or absent in reported cases. However, as many patients died suddenly from cardiac complications, the prognosis seems poor. Of those patients who survived, all underwent surgical intervention. Trans-thoracic echocardiography is the diagnostic modality of choice as it allows dynamic evaluation of intracardiac masses. Metastatic involvement of the heart from thyroid cancer is uncommon. Left untreated this complication seems likely to be fatal. Therefore, in patients with established thyroid malignancy who develop cardiac arrhythmias, new murmurs, or signs of cardiac decompensation, we suggest that cardiac metastases be considered. Echocardiography should be performed in patients with advanced thyroid cancer and cardiac symptoms or signs. If a cardiac metastasis is present, we recommend surgical intervention if possible.
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http://dx.doi.org/10.1089/thy.2010.0273DOI Listing
August 2011

Is fluorine 18 fluorodeoxyglucose positron emission tomography scanning a suitable diagnostic test for histologically active large-vessel vasculitis?

J Clin Rheumatol 2011 Jan;17(1):31-4

Rheumatology Unit, Department of Nuclear Medicine, Alfred Hospital, Commercial Road, Melbourne, Australia.

Recent publications have highlighted the use of fluorine 18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET) as a moderately sensitive, noninvasive diagnostic test for medium- and large-vessel vasculitis. We report the atypical case of a patient with biopsy-proven granulomatous vasculitis of the aorta in addition to a non-small cell lung cancer, whose whole-body F-FDG PET/computed tomography scan demonstrated metabolic activity within the lung malignancy but was metabolically inactive in the aorta. We submit that F-FDG PET may not be an accurate diagnostic test for histologically active large-vessel vasculitis and should be used with caution.
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http://dx.doi.org/10.1097/RHU.0b013e3182050d07DOI Listing
January 2011

Paraneoplastic syndromes in prostate cancer.

Nat Rev Urol 2010 Dec;7(12):681-92

Division of Urology, Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Grattan Street, Parkville, Melbourne, Victoria 3050, Australia.

Prostate cancer is the second most common urological malignancy to be associated with paraneoplastic syndromes after renal cell carcinoma. These syndromes tend to occur in the setting of late stage and aggressive tumors with poor overall outcomes. Recognition of these syndromes is clinically important as it might lead to the detection of underlying malignancy and impact on the treatment options available. The literature features around 100 cases of paraneoplastic syndromes associated with prostate cancer and these include endocrine manifestations, neurological entities, dermatological conditions, and other syndromes. Over 70% of cases document the syndrome as the initial clinical manifestation of prostate cancer, while in just under 20% the syndrome was an initial sign of disease progression to the castrate-resistant state. The vast majority of cases involved advanced metastatic malignancy. The syndromes generally resolve upon institution of treatment for the underlying prostate cancer, but some syndromes require specific therapies. Some syndromes are associated with serum markers that are readily detectable and demonstration of these putative markers within prostate cancer tissue at an individual level would firmly link the paraneoplastic syndrome with its underlying prostatic malignancy. The causes of paraneoplastic syndromes in prostate cancer are incompletely understood, and further research into their biology might shed more light on the complex molecular mechanisms that underpin prostate cancer and its lethal potential.
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http://dx.doi.org/10.1038/nrurol.2010.186DOI Listing
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http://dx.doi.org/10.1053/j.gastro.2008.09.007DOI Listing
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