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1.
Nat Commun ; 14(1): 3155, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37258531

ABSTRACT

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. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Humans , Neoadjuvant Therapy , Multiomics , Australia , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics
4.
J Clin Endocrinol Metab ; 102(6): 1926-1933, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28323985

ABSTRACT

Context: Patients with multiple endocrine neoplasia type 1 (MEN1) are at high risk of malignant pancreatic neuroendocrine tumors (pNETs). Structural imaging is typically used to screen for pNETs but is suboptimal for stratifying malignant potential. Objective: To determine the utility of fluorodeoxyglucose (18F) positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting the malignant potential of pNETs in MEN1. Design: Retrospective observational study. Setting: Tertiary referral hospital. Patients: Forty-nine adult patients with MEN1 carrying a common MEN1 mutation who underwent 18F-FDG PET/CT for MEN1 surveillance between 1 January 2010 and 30 September 2016. Interventions: Structural and functional imaging (magnetic resonance imaging, CT, ultrasonography, and 18F-FDG PET/CT) and surgical histopathology. Main Outcome Measures: pNET size, behavior, and histopathology. Results: Twenty-five (51.0%) of 49 patients studied had pancreatic lesions on structural imaging. Five (25%) of these had 18F-FDG-PET-avid lesions. In addition, two had solitary FDG-avid liver lesions, and one a pancreatic focus without structural correlate. Eight patients with pNETs underwent surgery (three FDG-avid lesions and five nonavid pNETs). The Ki-67 index was ≥5% in FDG-avid pNETs and <2% in nonavid pNETs. Overall, six of the eight (75%) patients with FDG-avid hepatopancreatic lesions harbored aggressive or metastatic NETs compared with one of 41 patients (2.4%) without hepatopancreatic FDG avidity [P < 0.001; sensitivity; 85.7% (95% confidence interval [CI], 48.7% to 99.3%); specificity, 95.2% (95% CI, 84.2% to 99.2%)]. Conclusion: 18F-FDG PET/CT is an effective screening modality in MEN1 for identifying pNETs of increased malignant potential. Surgical resection is recommended for FDG-avid pNETs.


Subject(s)
Liver Neoplasms/diagnostic imaging , Multiple Endocrine Neoplasia Type 1/complications , Neuroendocrine Tumors/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Adult , Female , Fluorodeoxyglucose F18 , Humans , Liver Neoplasms/secondary , Magnetic Resonance Imaging , Male , Middle Aged , Neuroendocrine Tumors/etiology , Neuroendocrine Tumors/secondary , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/etiology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Retrospective Studies , Tumor Burden , Ultrasonography
5.
BMJ Case Rep ; 20142014 Jan 08.
Article in English | MEDLINE | ID: mdl-24403388

ABSTRACT

The seat belt syndrome is a recognised complication of seat belt use in vehicles. Unstable Chance fractures of the spine without neurological deficits have been reported infrequently. We describe a young woman with completely disrupted Chance fracture of the second lumbar vertebra in association with left hemidiaphragmatic rupture/hernia, multiple bowel perforations, splenic capsular tear, left humeral shaft and multiple rib fractures. These injuries which resulted from high-speed vehicle collision and led to death of one of the occupants were readily detected by trauma series imaging. The patient was successfully treated by a dedicated multidisciplinary team which adopted a staged surgical approach and prioritisation of care. There were no manifested neurological or other deficits after 1 year of follow-up. To the authors' knowledge, this is the first report of such a case in Australasia. We discuss the challenging surgical management, highlighting the role of radiological imaging in such cases and provide a literature review.


Subject(s)
Accidents, Traffic , Fractures, Comminuted/diagnosis , Joint Dislocations/diagnosis , Lumbar Vertebrae/injuries , Multiple Trauma/diagnosis , Neurologic Examination , Seat Belts/adverse effects , Spinal Fractures/diagnosis , Adult , Cooperative Behavior , Female , Fractures, Comminuted/surgery , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Intensive Care Units , Interdisciplinary Communication , Joint Dislocations/surgery , Lumbar Vertebrae/pathology , Lumbar Vertebrae/surgery , Magnetic Resonance Imaging , Multiple Trauma/surgery , Patient Care Team , Postoperative Care/methods , Postoperative Complications/diagnosis , Spinal Fractures/surgery , Spinal Fusion/methods , Syndrome , Tomography, X-Ray Computed
6.
Surg Laparosc Endosc Percutan Tech ; 23(2): e84-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23579537

ABSTRACT

Hepatoportal arteriovenous fistulae are a rare cause of portal hypertension, which can have significant clinical manifestations. They have multiple etiologies, one of which includes hepatic trauma. We present a case of hepatoportal fistula presenting with bleeding esophageal varices in an 83-year-old man. The exact cause of fistula in this case is not entirely clear; however, hepatic trauma was noted in the patients' history, some 52 years before presentation. We also present a literature review on this rare and interesting phenomenon.


Subject(s)
Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/therapy , Embolization, Therapeutic/methods , Esophageal and Gastric Varices/therapy , Hypertension, Portal/diagnostic imaging , Abdominal Injuries/complications , Abdominal Injuries/diagnosis , Aged, 80 and over , Angiography/methods , Esophageal and Gastric Varices/diagnostic imaging , Follow-Up Studies , Hematemesis/diagnosis , Hematemesis/etiology , Humans , Hypertension, Portal/complications , Male , Risk Assessment , Severity of Illness Index , Time Factors , Tomography, X-Ray Computed/methods , Treatment Outcome , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis
8.
ANZ J Surg ; 80(10): 710-3, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21040331

ABSTRACT

BACKGROUND: Liver resection is a significant operation usually limited to large metropolitan hospitals. Liver resections were first performed at the Launceston General Hospital (LGH), a regional centre (bed capacity 280), in May 2000. This is a summary of liver resection at LGH. METHODS: Data of liver resections performed between May 2000 and March 2008 at LGH were collected retro-prospectively and reviewed with attention to patient survival, post-operative complications and mortality. RESULTS: There were 102 consecutive liver resections during the study period. Metastatic colorectal adenocarcinoma was the most frequent pathology (n = 61). Six patients had metastases from primaries other than colorectal cancer. There were 13 resections for primary liver malignancy, 2 from invasion by gallbladder carcinoma, 1 for contiguous invasion by gastric cancer and 19 were for benign conditions. Thirteen patients had post-operative wound infections and six had significant bile leaks. There were five deaths in-hospital (surgical mortality 4.9%). At the end of the study period, 51 cancer patients were still alive (14 with disease recurrences) and 30 have died (23 from recurrent diseases). Patients operated for colorectal cancer metastases achieved a 44% 5-year survival rate (median survival = 46 months). Patients with hepatocellular carcinoma had 3-year survival rate of 15% (median survival = 24 months). CONCLUSION: Resection provides the best hope of cure for patients with primary or secondary hepatic malignancy. With adequate expertise, liver resections can be performed safely in a regional hospital.


Subject(s)
Hepatectomy/statistics & numerical data , Liver Neoplasms/surgery , Adenocarcinoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Female , Hepatectomy/mortality , Hospitals, General , Humans , Liver Neoplasms/secondary , Male , Middle Aged , Postoperative Complications , Prospective Studies , Retrospective Studies
9.
Surg Laparosc Endosc Percutan Tech ; 18(6): 608-10, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19098671

ABSTRACT

Endoscopic retrograde cholangiopancreatography (ERCP) plays an important diagnostic and potentially therapeutic role in the management of a broad range of biliary and pancreatic disorders. However, it is an invasive procedure with an associated complication rate in the vicinity of 5% to 15% and mortality rate of 1%. We present an unusual case of a patient who sustained a stent-related duodenal perforation after undergoing ERCP. We reviewed the current literature in regard to risk factors, etiology, diagnosis, management, and prognosis of ERCP-related perforations, aiming to provide a brief, updated overview of this devastating complication.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Duodenum/injuries , Foreign-Body Migration/complications , Intestinal Perforation/etiology , Prosthesis Implantation/adverse effects , Stents/adverse effects , Aged , Fatal Outcome , Humans , Intestinal Perforation/diagnosis , Male , Prosthesis Implantation/instrumentation , Tomography, X-Ray Computed
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