The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy - results from the AGITG DOCTOR trial and the cancer evolution biobank.

A plateau in treatment effect can be seen for the current 'one-size-fits-all' approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures.

Hepatocellular carcinoma requiring liver transplantation in hereditary tyrosinemia type 1 despite nitisinone therapy and α1-fetoprotein normalization.

Background: Hereditary tyrosinemia type 1 is a rare metabolic condition associated with an increased risk of hepatocellular carcinoma. Nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione, NTBC) treatment has reduced but not eliminated the risk. The delayed initiation of nitisinone treatment, and persistently abnormal α1-fetoprotein (AFP) levels are recognized to be risk factors for late-onset hepatocellular carcinoma.

Fatal Respiratory Diphtheria Caused by ß-Lactam-Resistant Corynebacterium diphtheriae.

Background: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, β-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C.

Lymphocytic esophagitis: An Australian (Queensland) case series of a newly recognized mimic of eosinophilic esophagitis.

Background And Aim: Lymphocytic esophagitis (LoE) is a recently described upper gastrointestinal tract "disorder" diagnosis of which hinges on histology and is characterized by the excessive infiltration of lymphocytes in the peripapillary fields of the esophageal epithelium, with clinical manifestations similar to those of eosinophilic esophagitis (EoE). In this article, we aim to describe for the first time the clinico-pathological characteristics of a large cohort of Australian (Queensland) cases of LoE.

Methods: Histological data that fulfilled the criteria (predominant lymphocytic infiltration in the peripapillary fields, none or minimal neutrophils or eosinophils, and no infection) were collected between January 2014 and May 2016 from a number of major Queensland Public Hospital anatomical pathology laboratories.

Complex structural rearrangements are present in high-grade dysplastic Barrett's oesophagus samples.

Background: Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett's oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals.

Large frontal osseous hemangioma with dural sinus involvement in a patient with Klippel-Trenaunay syndrome: A rare case report.

Background: We present one of the first documented cases in the literature of an adult with Klippel-Trenaunay syndrome (KTS) with a large frontal osseous hemangioma.

Case Description: A 30-year-old male presented with a rapidly enlarging frontal skull lesion that had developed in only 3 months. Radiological investigation revealed a highly vascular lesion attached to the frontal bone.

A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care.

Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB-4], or enhanced liver fibrosis [ELF] test) are recommended as first-line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility.

Hepatic expression profiling identifies steatosis-independent and steatosis-driven advanced fibrosis genes.

Chronic liver disease (CLD) is associated with tissue-destructive fibrosis. Considering that common mechanisms drive fibrosis across etiologies, and that steatosis is an important cofactor for pathology, we performed RNA sequencing on liver biopsies of patients with different fibrosis stages, resulting from infection with hepatitis C virus (HCV) (with or without steatosis) or fatty liver disease. In combination with enhanced liver fibrosis score correlation analysis, we reveal a common set of genes associated with advanced fibrosis, as exemplified by those encoding the transcription factor ETS-homologous factor (EHF) and the extracellular matrix protein versican (VCAN).

HER2 testing in advanced gastric and gastro-oesophageal cancer: analysis of an Australia-wide testing program.

This Australian human epidermal growth factor receptor 2 (HER2) testing program aimed to analyse >800 cases tested in a coordinated setting to further evaluate the criteria to establish HER2 status in advanced gastric and gastro-oesophageal junction (GOJ) cancer. Heterogeneity, and minimum number of biopsy fragments for reliable HER2 assessment were also examined in a subset of samples. Five laboratories tested 891 samples referred to determine HER2 status for potential anti-HER2 treatment.

Multiplex Serum Protein Analysis Identifies Novel Biomarkers of Advanced Fibrosis in Patients with Chronic Liver Disease with the Potential to Improve Diagnostic Accuracy of Established Biomarkers.

Background And Aims: Non-invasive markers of liver fibrosis are urgently required, especially for use in non-specialist settings. The aim of this study was to identify novel serum biomarkers of advanced fibrosis.

Methods: We performed an unbiased screen of 120 serum analytes including cytokines, chemokines and proteases in 70 patients (35 without fibrosis, 35 with cirrhosis on biopsy), and selected a panel of 44 candidate biomarkers, which were subsequently measured in a mixed-etiology cohort of 432 patients with known serum HA, PIIINP and TIMP1 (which comprise the validated Enhanced Liver Fibrosis (ELF) test).

Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC.

Human papillomavirus status and p16(INK4A) expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia.

Background: The last decade has seen changes in the epidemiology of mucosal squamous cell carcinomas of the head and neck (HNSCCs), with increasing numbers of cases attributable to human papillomavirus (HPV) infection. We sought to determine the prevalence of HPV and p16(INK4a) expression in Australian HNSCC patients and to identify predictors of HPV-positivity.

Methods: We recruited 248 HNSCC patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx diagnosed between 2004 and 2010.

ELF score ≥9.8 indicates advanced hepatic fibrosis and is influenced by age, steatosis and histological activity.

Background & Aims: There is increasing need to identify individuals with advanced liver fibrosis, who are at risk of complications such as hepatocellular carcinoma. The commercially available enhanced liver fibrosis (ELF) test provides a non-invasive assessment of fibrosis severity. This study was designed to determine the diagnostic accuracy of the manufacturer's cut-off value (≥9.

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented.

Genome-wide analysis of esophageal adenocarcinoma yields specific copy number aberrations that correlate with prognosis.

The incidence of esophageal adenocarcinoma (EAC) has been increasing rapidly for the past 3 decades in Western (Caucasian) populations. Curative treatment is based around esophagectomy, which has a major impact on quality of life. For those suitable for treatment with curative intent, 5-year survival is ∼30%.

Is alpha-B crystallin an independent marker for prognosis in lung cancer?

Background: Alpha B-crystallin (CRYAB) is an oncogene that increases tumour survival by promoting angiogenesis and preventing apoptosis. CRYAB is an independent prognostic marker in epithelial tumours including head and neck squamous cell carcinoma and breast cancer where it is predictive of nodal status and associated with poor outcome. We explored the role of CRYAB in non-small-cell lung cancer (NSCLC).

Severe acute liver injury associated with lumiracoxib.

Background And Aim: Significant elevations in liver transaminases were noted in some patients during pre-marketing clinical trials with lumiracoxib, a selective COX-2 inhibitor. It was withdrawn from the Australian market in August 2007, because of an association with severe liver injury. We describe in detail three cases of severe liver injury in patients taking lumiracoxib

Methods: Three patients admitted to our hospital with severe liver injury and taking lumiracoxib are described in detail, together with information on a further six cases reported to the Australian Therapeutics Goods Administration (TGA), none of whom had pre-existing liver disease or obvious risk factors for liver disease.