Nephrotoxin-mediated kidney injury is an important clinical problem, as it can lead to acute kidney injury and chronic kidney disease. Both entities are associated with significant morbidity, increased hospitalisation, healthcare utilisation, and cardiovascular mortality. With the loss of kidney function, there is an accumulation of uraemic toxins, of which the protein-bound toxins—indoxyl sulphate and p-cresyl sulphate—can further inflict damage to the kidneys and the cardiovascular system, culminating in a vicious cycle. Therefore, it is imperative that clinicians have a firm understanding of the common causes and mechanisms of toxin-mediated kidney injury, as well as their clinical presentations and histopathologic features, in order to reduce the prevalence of this pernicious condition.

Reference range <30), CEA: <1.0 ng/mL (Reference range <3.5) and CA19.9: 16 U/mL (Reference range <35).Macroscopically, there was a disrupted cyst with a wall that is 1 to 3 mm in thickness and with solid cream fibrous areas up to 45 mm in size.Microscopic examination revealed an endometriotic cyst with solid areas within the cyst wall with a proliferation of endometrioid glands within a fibrous stroma and extensive squamous metaplasia.Areas of glandular complexity along with mild atypia and occasional mitoses are seen in keeping with endometrioid borderline tumour.Beta catenin immunohistochemistry showed aberrant staining suggestive of an underlying mutation.

Reference range <30), CEA: <1.0 ng/mL (Reference range <3.5) and CA19.9: 16 U/mL (Reference range <35).Macroscopically, there was a disrupted cyst with a wall that is 1 to 3 mm in thickness and with solid cream fibrous areas up to 45 mm in size.Microscopic examination revealed an endometriotic cyst with solid areas within the cyst wall with a proliferation of endometrioid glands within a fibrous stroma and extensive squamous metaplasia.Areas of glandular complexity along with mild atypia and occasional mitoses are seen in keeping with endometrioid borderline tumour.Beta catenin immunohistochemistry showed aberrant staining suggestive of an underlying mutation.

Acinar cystic transformation (ACT) of the pancreas is a rare benign lesion. We describe a case of ACT with progressive main pancreatic duct dilation concerning for malignancy, not previously described. We discuss the difficulties associated with imaging and biopsy in differentiating this pathology from other cystic lesions, including intraductal mucinous papillary neoplasms.

Renal fibroepithelial polyp (FEP) is a very rare tumour and we describe a case causing acute ureteric obstruction. A 56 year old lady presented with presumed pyelonephritis and left hydronephrosis, without calculi. She was transferred to a tertiary hospital urology service where after an unsuccessful retrograde attempt at stent insertion, a nephrostomy was inserted. Subsequently, the patient underwent a ureteropyeloscopy and excision of a FEP arising from the renal pelvis. Renal FEP is a very rare cause of obstruction and was successfully managed endoscopically.

ANZ Journal of SurgeryVolume 92, Issue 1-2 p. 271-273 IMAGES FOR SURGEONS Testicular seminoma metastases presenting as gastrointestinal malignancy: A case report and review of the literature Alice Thomson MBBS, Alice Thomson MBBS orcid.org/0000-0001-5278-1935 Department of Urology, Eastern Health, Box Hill, Victoria, Australia Contribution: ​Investigation, Writing - original draft, Writing - review & editingSearch for more papers by this authorBen Keong FRACS, MS, Ben Keong FRACS, MS Department of General Surgery, Eastern Health, Box Hill, Victoria, Australia Contribution: Writing - review & editingSearch for more papers by this authorAnthony Longano MBBS, FRCPA, Anthony Longano MBBS, FRCPA Department of Anatomical Pathology, Eastern Health, Box Hill, Victoria, Australia Contribution: Writing - review & editingSearch for more papers by this authorAnis Hamid FRACP, MBBS, Anis Hamid FRACP, MBBS orcid.org/0000-0002-7193-9723 Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia Contribution: Writing - review & editingSearch for more papers by this authorShomik Sengupta FRACS, MD, Shomik Sengupta FRACS, MD orcid.org/0000-0003-3357-1216 Department of Urology, Eastern Health, Box Hill, Victoria, Australia Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia Contribution: Conceptualization, ​Investigation, Writing - review & editingSearch for more papers by this author Alice Thomson MBBS, Alice Thomson MBBS orcid.org/0000-0001-5278-1935 Department of Urology, Eastern Health, Box Hill, Victoria, Australia Contribution: ​Investigation, Writing - original draft, Writing - review & editingSearch for more papers by this authorBen Keong FRACS, MS, Ben Keong FRACS, MS Department of General Surgery, Eastern Health, Box Hill, Victoria, Australia Contribution: Writing - review & editingSearch for more papers by this authorAnthony Longano MBBS, FRCPA, Anthony Longano MBBS, FRCPA Department of Anatomical Pathology, Eastern Health, Box Hill, Victoria, Australia Contribution: Writing - review & editingSearch for more papers by this authorAnis Hamid FRACP, MBBS, Anis Hamid FRACP, MBBS orcid.org/0000-0002-7193-9723 Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia Contribution: Writing - review & editingSearch for more papers by this authorShomik Sengupta FRACS, MD, Shomik Sengupta FRACS, MD orcid.org/0000-0003-3357-1216 Department of Urology, Eastern Health, Box Hill, Victoria, Australia Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia Contribution: Conceptualization, ​Investigation, Writing - review & editingSearch for more papers by this author First published: 17 June 2021 https://doi.org/10.1111/ans.17006Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume92, Issue1-2January/February 2022Pages 271-273 RelatedInformation

Background: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction. Methods: Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples: 404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and 440 pairs from the Women's Health Initiative (WHI) cohort. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication data sets using the area under the curve (AUC). Results: The meta-analysis identified associations (P < 4.7 x 10(-5)) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P < 0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication data set inMCCS [N = 134; odds ratio per SD(OR) = 1.37; 95% CI, 1.00-1.90] after confounder adjustment; AUC = 0.66, compared with AUC = 0.64 without methylation information. Limited evidence of replication was found in the second testing data set in WHI (N = 440; OR = 1.09; 95% CI, 0.91-1.30). Conclusions: Combination of smoking-associated methylation marks may provide some improvement to UC Crisk prediction. Our findings need further evaluation using larger data sets. Impact: DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.

ANZ Journal of SurgeryVolume 91, Issue 9 p. 1945-1947 IMAGES FOR SURGEONS Phlegmonous gastritis: an unusual mimic of gastric cancer Shalini Ponnampalam BMedSc(Hons), MD, Shalini Ponnampalam BMedSc(Hons), MD orcid.org/0000-0001-7164-782X Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia Contribution: Writing - original draft, Writing - review & editingSearch for more papers by this authorChristopher Seng Hong Lim MBBS, BSc (Med), MRCS (Edin), MS (Usyd), FRACS, Christopher Seng Hong Lim MBBS, BSc (Med), MRCS (Edin), MS (Usyd), FRACS orcid.org/0000-0003-4772-7170 Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia Contribution: Conceptualization, Supervision, Writing - review & editingSearch for more papers by this authorAnthony Longano MBBS (Hons), FRCPA, Anthony Longano MBBS (Hons), FRCPA Department of Anatomical Pathology, Eastern Health, Box Hill Hospital, Melbourne, Victoria, Australia Contribution: Formal analysis, ​InvestigationSearch for more papers by this authorEnoch Wong MBBS, FRACS, Enoch Wong MBBS, FRACS orcid.org/0000-0002-2983-4768 Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia Monash University Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia Contribution: Supervision, Writing - review & editingSearch for more papers by this authorAkhtar Sayed-Hassen BA, MBChB, FRCS (Ed), FRACS, Akhtar Sayed-Hassen BA, MBChB, FRCS (Ed), FRACS Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia Contribution: SupervisionSearch for more papers by this author Shalini Ponnampalam BMedSc(Hons), MD, Shalini Ponnampalam BMedSc(Hons), MD orcid.org/0000-0001-7164-782X Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia Contribution: Writing - original draft, Writing - review & editingSearch for more papers by this authorChristopher Seng Hong Lim MBBS, BSc (Med), MRCS (Edin), MS (Usyd), FRACS, Christopher Seng Hong Lim MBBS, BSc (Med), MRCS (Edin), MS (Usyd), FRACS orcid.org/0000-0003-4772-7170 Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia Contribution: Conceptualization, Supervision, Writing - review & editingSearch for more papers by this authorAnthony Longano MBBS (Hons), FRCPA, Anthony Longano MBBS (Hons), FRCPA Department of Anatomical Pathology, Eastern Health, Box Hill Hospital, Melbourne, Victoria, Australia Contribution: Formal analysis, ​InvestigationSearch for more papers by this authorEnoch Wong MBBS, FRACS, Enoch Wong MBBS, FRACS orcid.org/0000-0002-2983-4768 Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia Monash University Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia Contribution: Supervision, Writing - review & editingSearch for more papers by this authorAkhtar Sayed-Hassen BA, MBChB, FRCS (Ed), FRACS, Akhtar Sayed-Hassen BA, MBChB, FRCS (Ed), FRACS Upper Gastrointestinal Surgery Unit, Box Hill Hospital, Melbourne, Victoria, Australia Contribution: SupervisionSearch for more papers by this author First published: 15 January 2021 https://doi.org/10.1111/ans.16580Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume91, Issue9September 2021Pages 1945-1947 RelatedInformation

A 22-year-old Caucasian male with a four pack-year history of smoking presented due to one month of recurrent, moderate volume haemoptysis and some dyspnoea. There was no history of recent flu-like illness or other infection. He had no other occupational or recreational exposures relevant to these respiratory symptoms. There was no other significant medical history, including no history of previously detected haematuria or proteinuria. At initial work-up haemoglobin was 90 g/L, serum creatinine 77 μmol/L and eGFR >90 mL/min. ESR was raised at 35 mm/hr. Chest X-ray showed bilateral lower lobe patchy heterogeneous parenchymal opacities. There were 250 dysmorphic erythrocytes in urine and 0.5 g per day of proteinuria. Renal biopsy contained eleven glomeruli with one segmental necrotising lesion and two cellular crescents observed. The remaining glomeruli showed a mild and focal increase in mesangial cellularity. The tubules contained some luminal erythrocyte casts and no extraglomerular vasculitis was apparent. There was no interstitial fibrosis. Immunofluorescence demonstrated linear staining with IgG (Fig. 1A) and C3 along the glomerular basement membrane as well as prominent glomerular mesangial staining with IgA (Fig. 1B). Electron microscopy showed only the typical glomerular mesangial electron-dense deposits of IgA nephropathy. At this point anti-GBM serology (ELISA for IgG autoantibodies against the NC1 domain of alpha-3 collagen chain) returned as positive. In addition, ANA and dsDNA antibodies were not elevated. Both an ENA screen and ANCA antibodies were also negative. A final diagnosis of concurrent anti-GBM disease and IgA glomerulonephritis was made. Treatment consisted of a fixed course of 21 sessions of plasma exchange. In addition, oral prednisolone was commenced at 75 mg daily, tapering to 10 mg daily at 4 months and with intention to cease at 6 months. Oral cyclophosphamide was also commenced at 150 mg daily. It was ceased at 2 months and replaced with oral azathioprine at 100 mg daily. The patient had resolution of clinical symptoms, with normalisation of haemoglobin and negative anti-GBM serology at 4-month follow-up. Serum creatinine remained within the normal range, however there had been a slight increase in proteinuria to 0.7 g per day. Concurrent anti-GBM disease and ANCA-associated (pauci-immune) glomerulonephritis is a well-recognised phenomenon.1Rutgers A. Slot M. van Paassen P. et al.Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis.Am J Kidney Dis. 2005; 46: 253-262Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar Concurrent anti-GBM disease and immune complex-mediated glomerulonephritis is less common but also described,2Cui Z. Zhao M.H. Wang S.X. et al.Concurrent antiglomerular basement membrane disease and immune complex glomerulonephritis.Ren Fail. 2006; 28: 7-14Crossref PubMed Scopus (27) Google Scholar and amongst this group there are only four previous case reports that could be found in the literature of concurrent anti-GBM disease and IgA nephropathy.3Annamalai I. Chandramohan G. Srinivasa Prasad N.D. et al.Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: an unusual association.Saudi J Kidney Dis Transpl. 2017; 28: 1404-1407Crossref PubMed Scopus (10) Google Scholar, 4Ge Y.T. Liao J.L. Liang W. et al.Anti-glomerular basement membrane disease combined with IgA nephropathy complicated with reversible posterior leukoencephalopathy syndrome: an unsual case.Am J Case Rep. 2015; 16: 849-853Crossref PubMed Scopus (14) Google Scholar, 5Gao B. Li M. Xia W. et al.Rapidly progressive glomerulonephritis due to anti-glomerular basement memebrane disease accompanied by IgA nephropathy: a case report.Clin Nephrol. 2014; 81: 139-141Crossref Scopus (8) Google Scholar, 6Wang A. Wang Y. Wang G. et al.Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane disease.Mol Med Rep. 2012; 5: 1212-1214PubMed Google Scholar The current case presents some features of difference to the four cases referenced above. Firstly, the current case involves a Caucasian patient, whereas previous reports involved Asian patients. When taken together, this may reflect the well-established disparity in prevalence of IgA nephropathy between European and Asian populations. This reported disparity7Zhu L. Zhang H. The genetics of IgA nephropathy: an overview from China.Kidney Dis. 2015; 1: 27-32Crossref Google Scholar results in an Asian population prevalence of 30–60% versus a European population prevalence of 20–30%. Ethnic influences are highlighted when the North American population prevalence of 10% is subclassified, revealing a native North American prevalence of 38% and an African-American prevalence of 2%.7Zhu L. Zhang H. The genetics of IgA nephropathy: an overview from China.Kidney Dis. 2015; 1: 27-32Crossref Google Scholar At the genetic level, genome-wide association studies (GWAS) have cumulatively found 15 loci for IgA nephritis susceptibility, studied and validated across populations of both Asian and European ethnicity.7Zhu L. Zhang H. The genetics of IgA nephropathy: an overview from China.Kidney Dis. 2015; 1: 27-32Crossref Google Scholar Although the effects of some genes at these loci has been elucidated, (e.g., locus 1q32 coding for genetic variants in CFH, CFHR3 and CFHR1 that affect complement activation) the underlying genetic mechanism for the development of the clinical disease remains unknown. Secondly, the current patient had haemoptysis and dyspnoea, respiratory features not present in the previous reports. Interestingly, in three of these reports the smoking status of the patient was not disclosed and in one report the patient was described as a non-smoker. Smoking status is known to be a crucial factor in determining the risk of pulmonary haemorrhage in the setting of anti-GBM disease,8Donaghy M. Rees A.J. Cigarette smoking and lung haemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane.Lancet. 1983; 2: 1390-1393Abstract PubMed Scopus (217) Google Scholar and is the most likely explanation for the presence of respiratory symptoms in the current case. Thirdly, the current patient had only 22% of glomeruli with crescents, well below the figure described in the other patients. As indicated above, he came to clinical attention as the result of one month of respiratory symptoms, in the absence of symptoms directly referable to the kidneys. The patients whose cases have previously been reported describe durations of illness between one week and two months prior to presentation.3Annamalai I. Chandramohan G. Srinivasa Prasad N.D. et al.Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: an unusual association.Saudi J Kidney Dis Transpl. 2017; 28: 1404-1407Crossref PubMed Scopus (10) Google Scholar, 4Ge Y.T. Liao J.L. Liang W. et al.Anti-glomerular basement membrane disease combined with IgA nephropathy complicated with reversible posterior leukoencephalopathy syndrome: an unsual case.Am J Case Rep. 2015; 16: 849-853Crossref PubMed Scopus (14) Google Scholar, 5Gao B. Li M. Xia W. et al.Rapidly progressive glomerulonephritis due to anti-glomerular basement memebrane disease accompanied by IgA nephropathy: a case report.Clin Nephrol. 2014; 81: 139-141Crossref Scopus (8) Google Scholar, 6Wang A. Wang Y. Wang G. et al.Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane disease.Mol Med Rep. 2012; 5: 1212-1214PubMed Google Scholar Hence the relatively low number of glomerular crescents in this patient is not due to a particularly early clinical presentation, but rather due to his anti-GBM disease being slanted towards respiratory effects most likely as a result of smoking. Many patients with a respiratory-slanted presentation of anti-GBM disease have a history of smoking, a recent flu-like illness or other infection.9Canney M. O’Hara P.V. McEvoy C.M. et al.Spatial and temporal clustering of anti-glomerular basement membrane disease.Clin J Am Soc Nephrol. 2016; 11: 1392-1399Crossref PubMed Scopus (60) Google Scholar A minority have a history of hydrocarbon exposure.10Bombassei G.J. Kaplan A.A. The association between hydrocarbon exposure and anti-glomerular basement membrane antibody-mediated disease (Goodpasture’s syndrome).Am J Ind Med. 1992; 21: 141Crossref PubMed Scopus (101) Google Scholar While a precise mechanistic interaction between IgA glomerulonephritis and anti-GBM disease remains undescribed, some reports put forth putative pathogenic relationships. There is a suggestion3Annamalai I. Chandramohan G. Srinivasa Prasad N.D. et al.Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: an unusual association.Saudi J Kidney Dis Transpl. 2017; 28: 1404-1407Crossref PubMed Scopus (10) Google Scholar, 5Gao B. Li M. Xia W. et al.Rapidly progressive glomerulonephritis due to anti-glomerular basement memebrane disease accompanied by IgA nephropathy: a case report.Clin Nephrol. 2014; 81: 139-141Crossref Scopus (8) Google Scholar, 6Wang A. Wang Y. Wang G. et al.Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane disease.Mol Med Rep. 2012; 5: 1212-1214PubMed Google Scholar that the deposition of immune complexes in glomeruli and the release of inflammatory mediators such as IL-1, TNF and IL-6 can induce conformational changes in the glomerular basement membrane. This leads to the exposure of cryptic antigen sites and immune response to the previously sequestered antigens, including the production of anti-glomerular basement membrane antibodies. Abnormalities of IgA molecules in IgA glomerulonephritis may also serve as a link to the development of anti-GBM disease. A defect in galactosylation of IgA1, both in serum and in elution from nephrectomy specimens has been identified in patients with IgA glomerulonephritis.2Cui Z. Zhao M.H. Wang S.X. et al.Concurrent antiglomerular basement membrane disease and immune complex glomerulonephritis.Ren Fail. 2006; 28: 7-14Crossref PubMed Scopus (27) Google Scholar Serum autoantibodies against this abnormal IgA1 were IgG2 subclass predominant. Some patients with anti-GBM disease combined with IgA glomerulonephritis demonstrated deposits of IgA1 with aberrant polysaccharide chain along the GBM and anti-GBM IgG2. It could thus be speculated that the deposition of the abnormal IgA1 along the GBM might lead to novel antigen formation and the production of the anti-GBM antibodies.2Cui Z. Zhao M.H. Wang S.X. et al.Concurrent antiglomerular basement membrane disease and immune complex glomerulonephritis.Ren Fail. 2006; 28: 7-14Crossref PubMed Scopus (27) Google Scholar In summary, this report substantiates the documented occurrence of anti-GBM disease in concert with IgA nephropathy. It also looks at some aspects of pathogenesis, and widens the clinical and histopathological spectrum of features described in conjunction with this phenomenon. The authors state that there are no conflicts of interest to disclose.

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 ERBB4 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 ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.

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.

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.

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.

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.

Epithelioid haemangioendothelioma is a rare low grade malignant vascular tumour with an estimated prevalence of less than one in one million. It may occur at any age with a mean age of presentation of 36 years and most commonly affects the liver and lung. Approximately 14% of epithelioid haemangioendotheliomas occur as primary lesions of bone of which the long bones of the extremities are the most common sites of involvement. We present a rare case of an epithelioid haemangioendothelioma involving the skull of an 11 year old girl. The patient initially presented with a protuberant mass in the parietal-occipital region on a background of recurrent headaches. MRI and CT scanning revealed a large partially calcified temporal-parietal-occipital mass in continuity with the calvarium. Biopsy of the lesion was performed which revealed a vasoformative tumour composed of polygonal and spindled cells in a focally chondromyxoid stroma. No multilayering of cells was seen and mitotic activity was inconspicuous. Immunohistochemistry showed co-expression of CD31 and cytokeratin. The patient underwent tumour embolisation and subsequent craniotomy with subtotal tumour resection. The clinical and pathological features of this case will be discussed with a review of the literature.

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.

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.