Browsing by Subject "Carcinoma"

Now showing 1 - 7 of 7
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    A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma
    (Elsevier, 2021) Chalasani, Naga P.; Ramasubramanian, Tiruvidaimarudur S.; Bhattacharya, Abhik; Olson, Marilyn C.; Edwards, David K., V; Roberts, Lewis R.; Kisiel, John B.; Reddy, K. Rajender; Lidgard, Graham P.; Johnson, Scott C.; Bruinsma, Janelle J.; Medicine, School of Medicine
    Background & aims: Hepatocellular carcinoma (HCC) can be treated effectively if detected at an early stage. Recommended surveillance strategies for at-risk patients include ultrasound with or without α-fetoprotein (AFP), but their sensitivity is suboptimal. We sought to develop a novel, blood-based biomarker panel with improved sensitivity for early-stage HCC detection. Methods: In a multicenter, case-control study, we collected blood specimens from patients with HCC and age-matched controls with underlying liver disease but without HCC. Ten previously reported methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins, including AFP, were assayed and analyzed by a logistic regression algorithm to predict HCC cases. The accuracy of the multi-target HCC panel was compared with that of other blood-based biomarkers for HCC detection. Results: The study included 135 HCC cases and 302 controls. We identified a multi-target HCC panel of 3 MDMs (HOXA1, EMX1, and TSPYL5), B3GALT6 and 2 protein markers (AFP and AFP-L3) with a higher sensitivity (71%, 95% CI: 60-81%) at 90% specificity for early-stage HCC than the GALAD score (41%, 95% CI: 30-53%) or AFP ≥7.32 ng/mL (45%, 95% CI: 33-57%). The AUC for the multi-target HCC panel for detecting any stage HCC was 0.92 compared with 0.87 for the GALAD score and 0.81 for AFP alone. The panel performed equally well in important subgroups based on liver disease etiology, presence of cirrhosis, or sex. Conclusions: We developed a novel, blood-based biomarker panel that demonstrates high sensitivity for early-stage HCC. These data support the potential for liquid biopsy detection of early-stage HCC to clinically benefit at-risk patients.
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    Author Correction: CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity
    (Nature Publishing Group, 2018-04-13) Walton, Josephine B.; Farquharson, Malcolm; Mason, Susan; Port, Jennifer; Kruspig, Bjorn; Dowson, Suzanne; Stevenson, David; Murphy, Daniel; Matzuk, Martin; Kim, Jaeyeon; Coffelt, Seth; Blyth, Karen; McNeish, Iain A.; Biochemistry and Molecular Biology, School of Medicine
    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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    Clinicogenomic Landscape of Metastatic Thymic Epithelial Tumors
    (American Society of Clinical Oncology, 2023) Ardeshir-Larijani, Fatemeh; Schneider, Bryan P.; Althouse, Sandra K.; Radovich, Milan; Masood, Ashiq; Perna, Fabiana; Salman, Huda; Loehrer, Patrick J.; Medicine, School of Medicine
    Background: Despite favorable clinical outcomes, a subset of patients with thymic epithelial tumors (TETs) develop metastasis. The Cancer Genome Atlas (TCGA) provides genomic data on primary TETs (pTETs). This study assessed the molecular alterations and uncovered targetable pathways in metastatic TETs (mTETs). Methods: From 2015 to 2020, 49 patients with stage IV TETs underwent Clinical Laboratory Improvement Amendments-based sequencing using whole-exome sequencing (n = 33), panel-based testing (n = 12), and/or liquid biopsy (n = 24). Specimens were obtained from a metastatic organ (n = 36) or relapsed primary mediastinal mass (n = 10), whereas four patients underwent a liquid biopsy only. Data on pTETs were derived from the TCGA. Results: Compared with the pTET data set, patients with mTETs were younger (54 years v 60.5 years, P = .009) and had more aggressive histologies, with the most common tumor type being thymic carcinoma (n = 22, 40.7%) and B3 thymoma (n = 15, 27.8%). GTF2I was the most altered gene in primary thymomas (48.80%, n = 60). In metastatic thymoma and thymic carcinoma, TP53 was the most common genetic alteration (31% and 36%, respectively). In mTETs, the genomic alteration occurred in the TP53/CDK, EGFR/RAS, and PI3K/mTOR pathways. Biopsies obtained from distant metastasis were more commonly found to contain targetable mutations. There was an overlap of 61% (22 of 36) between tissue and liquid biopsy genomic alterations. Conclusion: Clinically actionable genomic alterations are frequently observed in mTETs, indicating a value of repeat biopsy (preferably from a metastatic site of TETs for sequencing at the time of recurrence (TCGA data).
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    Intraductal carcinoma of the prostate is not a diagnostic entity
    (Wiley, 2021) Delahunt, Brett; Egevad, Lars; Samaratunga, Hemamali; Srigley, John R.; Cheng, Liang; Clouston, David; Furusato, Bungo; Kench, James; Leite, Katia R. M.; MacLennan, Gregory T.; Moch, Holger; Pan, Chin-Chen; Ro, Jae; Tsuzuki, Toyonori; van der Kwast, Theodorus; Wheeler, Thomas; Yaxley, John W.; Pathology and Laboratory Medicine, School of Medicine
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    Nephron-sparing management of upper tract urothelial carcinoma
    (Korean Urological Association, 2021-07) Farrow, Jason M.; Kern, Sean Q.; Gryzinski, Gustavo M.; Sundaram, Chandru P.; Urology, School of Medicine
    Urothelial carcinoma of the upper urinary tract is uncommon and presents unique challenges for diagnosis and management. Nephroureterectomy has been the preferred management option, but it is associated with significant morbidity. Nephron-sparing treatments are a valuable alternative and provide similar efficacy in select cases. A PubMed literature review was performed in English language publications using the following search terms: urothelial carcinoma, upper tract, nephron-sparing, intraluminal and systemic therapy. Contemporary papers published within the last 10 years were primarily included. Where encountered, systematic reviews and meta-analyses were given priority, as were randomized controlled trials for newer treatments. Core guidelines were referenced and citations reviewed for inclusion. A summary of epidemiological data, clinical diagnosis, staging, and treatments focusing on nephron-sparing approaches to upper tract urothelial carcinoma (UTUC) are outlined. Nephron-sparing management strategies are viable options to consider in patients with favorable features of UTUC. Adjunctive therapies are being investigated but the data remains mixed. Protocol variability and dosage differences limit statistical interpretation. New mechanisms to improve treatment dwell times in the upper tracts are being designed with promising preliminary results. Studies investigating systemic therapies are ongoing but implications for nephron-sparing management are uncertain. Nephron-sparing management is an acceptable treatment modality best suited for favorable disease. More work is needed to determine if intraluminal and/or systemic therapies can further optimize treatment outcomes beyond resection alone.
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    Orbital Exenteration for Craniofacial Lesions: A Systematic Review and Meta-Analysis of Patient Characteristics and Survival Outcomes
    (MDPI, 2023-08-27) Qedair, Jumanah; Haider, Ali S.; Balasubramanian, Kishore; Palmisciano, Paolo; Hassan, Taimur; Shahbandi, Ataollah; Sabahi, Mohammadmahdi; Kharbat, Abdurrahman F.; Abou-Al-Shaar, Hussam; Yu, Kenny; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Bin-Alamer, Othman; Neurological Surgery, School of Medicine
    Background: The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS). Methods: Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes. Results: A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9-68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8-33.4), a weighted overall mortality rate of 39% (95% CI: 28-50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46-83]). The OS multivariable analysis did not show any significant findings. Conclusions: Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted.
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    Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy
    (Elsevier, 2017-08) Thomas, Derek E.; Medicine, School of Medicine
    We performed a single-institution retrospective analysis of 137 patients with muscle-invasive urothelial carcinoma who underwent neoadjuvant chemotherapy and radical cystectomy to assess the prognostic significance of carcinoma in situ (CIS). The pathologic complete response rates were significantly decreased for patients with CIS identified on transurethral resection of the bladder tumor before treatment. The long-term follow-up data from patients with isolated CIS at cystectomy revealed prolonged progression-free and overall survival.