Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.
Pancreatic cancer (PC) is one of the most common forms of malignant tumors and causes of tumor-related death worldwide. The current prognosis of PC still remains poor due to the lack of effective early detection method. Recently, there is strong support that circulating miRNAs can be used as biomarkers for early detection of various cancers, including PC. The purpose of this review is to provide an overview of previous published studies on circulating miRNAs in plasma/serum for early detection of PC and summarize their diagnostic value. PubMed, Embase and Web of Science were systematically searched for eligible studies on circulating miRNAs for PC detection. Overall, 29 studies published between 2009 and 2018 evaluating 51 individual miRNAs (no P-value exceeding 0.05) and 13 miRNAs panels were included. Generally, the diagnostic performance of circulating miRNAs for PC detection was strong, with both the sensitivity and specificity of 36% individual miRNAs and 40% miRNAs panels exceeding 80%. Moreover, two promising miRNA panels were discovered and verified externally with all AUC values exceeding 0.95. Therefore, circulating miRNAs may hold potential to be used as noninvasive diagnostic biomarkers for PC, but large-scale studies are still needed to validate the promising miRNAs and optimize the miRNA panels. Since, the tremendous heterogeneity of studies in this field hampers translating miRNA markers into clinical practice, miRNA analytical procedures are also needed to be standardized in the future.
Background Prolonged pre‐treatment wait times in head and neck cancer are associated with increased morbidity and reduced survival. Traditional metrics exclude delays prior to biopsy, which represents an important and measurable period of time. This study aims to describe total wait time for head and neck cancer patients in our institution, to define a more accurate representation of the clinically relevant pre‐treatment wait time, and to evaluate predictive factors for prolonged wait times. Methods A retrospective review of head and neck cancer patients treated over 2 years in a tertiary referral centre was conducted. Patient demographics, referral symptoms, tumour details, treatment plan and key dates were analysed to identify total wait time and factors predictive of increased wait time. Results Two hundred and ninety‐four patients were included. Mean total wait time from initial referral to treatment initiation was 71.6 (median 61) days. The period from referral to biopsy represented 29% of mean total wait time. Factors predictive of increased wait time included presenting symptom of hoarseness, laryngeal cancer and treatment with definitive radiotherapy. Conclusions This study demonstrates that time from referral to biopsy represents a significant portion of total wait time, and we suggest that this be incorporated into future wait time metrics for improved clinical relevance. Furthermore, we have identified factors predicting increased wait time which can be targeted for future service improvement.
The MARF may be considered as an alternative to myocutaneous rectus free flap particularly for the reconstruction of maxillary defects in patients with central obesity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:137-141, 2017.
Aortoduodenal fistula 2 years after elective endovascular repair of an abdominal aortic aneurysm Aortoenteric fistula (AEF) is a rare complication after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA). 1 An AEF is a pathological connection between the aorta and gastrointestinal tract that is invariably life-threatening. Primary AEFs occur de novo due to mechanical factors, aortic inflammation or infection. Secondary AEFs commonly involve a previously placed aortic graft. Almost all secondary AEF occur after open AAA repair but cases following EVAR are reported. 1-6 We present our experience with this rare complication, which is unique because it was only identified at time of operation. An 85-year-old female with a history of chronic lymphocytic leukaemia on ibrutinib and atrial fibrillation on rivaroxaban was referred to a vascular surgeon with a 38 × 30 mm incidental saccular infrarenal aortic aneurysm. There was no clinical evidence that the aneurysm was mycotic. She underwent an uncomplicated endovascular graft repair using a Gore Excluder AAA Endograft (W. L. Gore & Associates, Inc.; Newark, Delaware, US). Follow-up duplex ultrasound at 24 months post-operatively demonstrated a patent stent graft with no evidence of endoleak. Twenty-five months post-operatively, the patient developed left lower quadrant abdominal pain, night sweats and constipation. She denied any gastrointestinal bleeding. Investigation of her abdominal pain including a colonoscopy did not identify a cause. She
Background: There is no registry data on morbidity and mortality of high-risk cutaneous squamous cell carcinoma (cSCC) in Australia.Aim: To examine the clinicopathological features, mortality and morbidity in high-risk cSCC patients in Western Australia (WA).Methods: A retrospective cohort study was conducted through hospital record review on cSCC patients discussed at multidisciplinary meetings at the two largest WA hospitals between March 2015 and December 2016.Results: Of 141 patients, 129 were evaluable, with median follow up of 43.9 (range 3.0-53.2) months. Patients were predominantly older males (84%) with significant comorbidities (Charlson Comorbidity Index (CCI) ≥5; 76%) and history of previous nonmelanoma skin cancer (57%) with advanced disease (57% stage IV without distant metastasis; American Joint Committee on Cancer, 7th edition). Pathological high-risk features were common including nodal extracapsular extension (47%) and cranial nerve involvement (16%). Clinical morbidity was significant with a median of 2 (range 0-13) excisions and 2 (range 0-21) cSCC-related hospitalisations for any cSCC event following the index case discussion. Recurrences of the primary index lesion occurred in 60% of patients and 20% had ≥2 recurrences. Median overall survival for patients with nonmetastatic disease was 39.8 (range 25.9-53.7) months and 16.1 (range 0.2-32.0) months for metastatic disease. CCI ≥5, advanced nodal stage and ≥2 recurrences were significantly associated with mortality on multivariable analyses (P < 0.05). Nodal extracapsular extension and any recurrences were identified as significant risk factors for disease-specific mortality on multivariable analyses (P < 0.05). Conclusion:High-risk cSCC patients have significant health needs represented by high-baseline comorbidities, multiplicity of cSCC events and the number of healthcareassociated interventions. There is an unmet need for robust cancer data collection.
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