Publications by authors named "Christopher Toon"

The liver is the most frequent and often the only site of distant disease in colorectal cancer and, of all treatment protocols currently in use, resection is the most likely to result in long-term cure. Within the liver, tumour proximity to major vasculature and biliary structures poses a resection challenge, requiring a balance of achieving negative margins while preserving adequate vascular circulation and biliary drainage. The focus on parenchymal sparing resections are important but just as important may be the 'biological' behaviour of the tumour.

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Background: Juvenile polyposis syndrome (JPS) is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the or gene. It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults. Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up.

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Article Synopsis
  • Cutaneous squamous cell carcinoma (cSCC) usually has a good prognosis, but some cases progress aggressively, with lymphovascular invasion (LVI) being a significant, yet under-researched, factor in these outcomes.
  • A study analyzed 486 cSCC cases over five years, finding LVI in 9.2% of patients, and its presence correlated with deeper tumors, specific locations, and larger sizes.
  • Patients with LVI showed significantly lower overall survival rates at 2 years (37.1% vs. 66.6%), indicating that LVI is an important independent marker of poor prognosis and should be included in future risk assessment systems for cSCC.
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Purpose: Granular cell tumours (GCTs) of the pancreas are mostly benign and exceptionally rare, with no unique identifying radiological features. Following a case discussion of a patient with GCT, a comprehensive review of available literature was conducted to identify the common diagnostic features associated with GCT.

Methods: Following a case report identified in our institution, a systematic review was conducted by two authors in accordance with Preferred Reporting Items for Systematic review and Meta-Analysis protocols (PRISMA) guidelines.

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Immunoglobulin G4-related disease (IgG4-RD) of the ureter is a rarely reported disease, often mimicking urothelial carcinoma. This paper describes a case of an otherwise healthy patient with a lesion involving the ureter revealed on Computed tomography (CT), avid on fludeoxyglucose positron emission tomography (FDG PET), that prior to surgery was suspicious for urothelial carcinoma, until intra-op frozen section revealed otherwise. Diagnosis of ureteral IgG4-RD should be considered as a differential diagnosis, with serum IgG4 levels obtained.

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  • p53 immunohistochemistry is being studied to improve the assessment of dysplasia in Barrett's mucosa, but current research on staining patterns is limited.
  • In a study of 28 sections from 23 patients, different p53 staining patterns were observed in non-neoplastic and dysplastic Barrett's tissue, with non-neoplastic areas showing weak and localized staining.
  • Dysplastic areas displayed stronger p53 expression with distinct patterns: a "crypt predominant" pattern in low-grade dysplasia and a more "diffuse" pattern in high-grade dysplasia, which may help in diagnosing dysplasia in biopsies.
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Glioblastoma, WHO-grade IV glioma, carries a dismal prognosis owing to its infiltrative growth and limited treatment options. Glioblastoma-derived extracellular vesicles (EVs; 30-1000 nm membranous particles) influence the microenvironment to mediate tumor aggressiveness and carry oncogenic cargo across the blood-brain barrier into the circulation. As such, EVs are biomarker reservoirs with enormous potential for assessing glioblastoma tumors in situ.

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The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma.

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Eosinophilic angiocentric fibrosis (EAF) is a rare, benign condition affecting the respiratory mucosa and is generally characterized by a locally destructive growth. We present a case of a lady with a saddle nose deformity that had for many years been treated as granulomatosis with polyangiitis (GPA), of which saddle nose deformity is a classic feature. At the time of surgery, she was found to have subglottic stenosis another classic feature of GPA, however, histology demonstrated EAF.

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Aims: Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within 1 year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help to guide treatment.

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Article Synopsis
  • - The rise in diagnoses of pancreatic neuroendocrine tumors (PanNETs) is largely due to improved detection methods, posing new challenges for treatment management.
  • - Whole-genome sequencing of 102 primary PanNETs revealed key genomic events, including a mutation in the MUTYH gene that impairs DNA repair, which is linked to several germline mutations found in 17% of patients.
  • - Somatic mutations affecting genes related to chromatin remodeling, DNA repair, mTOR signaling, and telomere maintenance were common, and some tumors exhibited unique characteristics associated with hypoxia and HIF signaling.
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Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes.

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SMARCB1 is a tumor suppressor gene that encodes for the protein INI1. SMARCB1 is commonly inactivated and INI1 correspondingly shows loss of expression in a range of malignant neoplasms including rhabdoid tumors, renal medullary carcinomas, and epithelioid sarcomas. Loss of INI1 expression has recently been reported in occasional gastrointestinal adenocarcinomas.

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The identification of somatic calreticulin (CALR) mutations can be used to confirm the diagnosis of a myeloproliferative disorder in Philadelphia chromosome-negative, JAK2 and MPL wild type patients with thrombocytosis. All pathogenic CALR mutations result in an identical C-terminal protein and therefore may be identifiable by immunohistochemistry. We sought to test the sensitivity and specificity of mutation specific immunohistochemistry for pathogenic CALR mutations using a commercially available mouse monoclonal antibody (clone CAL2).

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Germline mutations of the BAP1 gene have been implicated in a cancer predisposition syndrome which includes mesothelioma, uveal melanoma, cutaneous melanocytic lesions, renal cell carcinoma, and possibly other malignancies. Double hit inactivation of BAP1 with subsequent loss of expression of the BAP1 protein also occurs in approximately 50% of mesotheliomas. The link between BAP1 mutation and lung cancer is yet to be fully explored.

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Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma.

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Article Synopsis
  • An integrated genomic study of 456 pancreatic ductal adenocarcinomas identified 32 mutated genes organized into 10 key pathways affecting cancer development.
  • The analysis categorized the tumors into four distinct subtypes: squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX), each linked to unique histopathological traits.
  • Findings indicate that squamous tumors have poor prognosis and specific mutations, pancreatic progenitor tumors express developmental genes, ADEX tumors are linked to KRAS activation, and immunogenic tumors involve immune suppression networks, suggesting diverse molecular pathways for potential treatments.
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