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Department of Pathology and Laboratory Medicine

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Now showing 1 - 6 of 6
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    Intraoperative Margin Analysis Does Not Improve Outcomes in Treatment-Naive or Neoadjuvantly-Treated Patients With Pancreatic Ductal Adenocarcinoma
    Li, X.; Malik, P.; Bhalla, A.; McAuliffe, J.C.; Panarelli, N.C. (Elsevier, 2025-06-20)
    The prognostic relevance of intraoperative frozen section (IOF) margin analysis for patients with pancreatic ductal adenocarcinoma (PDAC) is debatable in both those treated with upfront surgery and neoadjuvant therapy. We analyzed the impact of intraoperative and final microscopic margin clearance in neoadjuvantly treated (n=71) and treatment naive (n=109) patients with PDAC. Overall survival (OS) was longer in the treatment naive (43 months) compared to the neoadjuvant (27 months) cohort (p=0.02). Overall, 24 (34%) patients in the neoadjuvant and 22 (20%) patients in the treatment naive group had positive final margins, 13 and 10 of which were detected intraoperatively, respectively. At a median follow-up of 21 months, recurrence rates were 65% in the treatment naive and 66% in the neoadjuvant cohort and were similar regardless of margin status assessed via IOF or permanent sections. Disease free survival (DFS) was significantly shorter in treatment naive patients with positive (11 months) compared to negative (30 months) final margins (p=0.03). Neither IOF nor final margin status was significantly associated with DFS in neoadjuvantly treated patients, nor were they associated with OS in either cohort. Multivariate analysis showed that lymphovascular, and perineural invasion were significantly associated with DFS, and lymphovascular invasion was significantly associated with OS. Our results suggest that IOF of selected margins does not correlate with survival and is of limited utility in treatment naive and neoadjuvantly treated PDAC patients.
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    Sankey diagrams: A simple, intuitive way to visualize and analyze complex, convoluted transfusion medicine operations data
    Chen, D.; Parra, P.; Benabdessadek, D.; Spinelli, J.; Desai, P.; Ong, S.; Racine-Brzostek, S.; Jimenez, A.; Cushing, M.M.; DeSimone, R.A.; Cohen, T. (Wiley, 2025-06-09)
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    Magic 8 Balls and psychics: Results of a National Survey of programme directors on their novel recruitment strategies in a post-grade era.
    Greisman, L.; Katz, S. (Wiley, 2025-05-20)
    Over the last decade, US residency programmes have seen a drastically changing landscape that is teaming with prospective applicants yet barren of grades. To discover how programme directors are rising to the challenge of recruiting applicants in the grade-free era, we conducted a methodologically rigorous (fictional) survey. Our (fabricated) empirical evidence offers insights into how programme directors are sifting through thousands of applicants who all sound the same. Additionally, we summarize the recent events and literature to contextualize how we arrived in the 'grade-free era' and share (real) innovations in recruitment that programmes have implemented.
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    Analysis of Concurrent Intracholecystic Papillary Neoplasms and Biliary Intraepithelial Neoplasia Reveals Distinct Histologic and Molecular Profiles
    Malik, P.; Krishnamurthy, K.; Sheikh, F.N.; Goldstein, D.Y.; Panarelli, N.C. (College of American Pathologists, 4/9/25)
    CONTEXT: Intracholecystic papillary neoplasms (ICPNs) and biliary intraepithelial neoplasia (BilIN) are presumed precursors to gallbladder adenocarcinomas, but their relationship is incompletely understood. OBJECTIVE: To perform morphologic and molecular characterization of concurrent ICPNs, nonpolypoid mucosa, and adenocarcinomas to determine whether these lesions are related at the DNA level. DESIGN: Background mucosa and 36 ICPNs were graded by a pathologist blinded to original diagnoses. Separate areas of ICPNs (n = 5), nondysplastic adjacent mucosa (n = 8), and invasive adenocarcinoma (n = 3) were amplified and sequenced on a next-generation sequencer. Data were manually curated to identify pathogenic somatic variants. RESULTS: High-grade ICPNs were associated with low-grade (n = 1) or high-grade (n = 3) BilIN or no dysplasia (n = 5). Fifteen were associated with invasive adenocarcinoma. Low-grade ICPNs were associated with low-grade BilIN (n = 3) or no dysplasia (n = 9). Pathogenic variants included CTNNB1 (catenin beta 1) exon 3 (7); TP53 (tumor protein p53) (6); APC (APC regulator of WNT signaling pathway) (2); RB1 (RB transcriptional corepressor 1) (1); KRAS (KRAS proto-oncogene, GTPase) (1); and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) (1). Pathogenic variants in ICPNs were not detected in BilIN or nondysplastic mucosa. Mutations in invasive cancers included TP53, PIK3CA, and RB1, concordant with the ICPN, but not with BilIN, in all 3 cases. CONCLUSIONS: IN in the background of ICPNs was of the same or lower grade than ICPNs. Synchronous ICPNs and BilIN lacked concordant somatic mutations. Mutations in adenocarcinomas aligned with the ICPNs. This suggests that ICPN and BilIN are independent at the DNA level and that the presence of ICPNs may not imply risk for subsequent flat dysplasia elsewhere in the biliary tree.
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    Targeting anti-androgen therapy resistance through epigenetic rewiring.
    Dunmore, K.E.; Rickman, D.S. (Nature Research, 4/1/25)
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    Exome sequencing reveals a sparse genomic landscape in Kaposi sarcoma.
    Phipps, W.; Bhinder, B.; Towlerton, A.; Mooka, P.; Kafeero, J.; Fitzgibbon, M.; Elemento, O.; Cesarman, E. (American Association for Cancer Research, 1/30/25)
    Kaposi Sarcoma (KS) is a frequently aggressive malignancy caused by Kaposi sarcoma herpesvirus (KSHV/HHV-8). People with immunodeficiencies, including HIV, are at increased risk for developing KS, but our understanding of the contributions of the cellular genome to KS pathogenesis remains limited. To determine if there are cellular genetic alterations in KS that might provide biological or therapeutic insights, we performed whole exome sequencing on 78 KS tumors and matched normal control skin from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda. We found a very low mutational burden in all but one specimen (median=11 mutations), which is the lowest number of mutations among all 33 tumor types in The Cancer Genome Atlas (TCGA). No recurrent mutations were seen and the most commonly affected oncogenic pathway was RTK/RAS. Mutational signatures included defective DNA mismatch repair and smoking. There was no evidence suggesting that multiple tumors from the same patient originated from the same original clone. The number of genome copy alterations per genome were higher in tumors from those without HIV infection and in tumors from participants with advanced stage disease, suggesting that lesions that take longer to develop may accumulate more alterations, although the number of alterations remain low compared to other cancers. Implications: Our findings indicate that the pathogenesis of KS differs from other malignancies, and that the primary driver of carcinogenesis is KSHV viral infection and expression of viral oncogenes, rather than clonal oncogenic transformation.