bd4abbcc92eb20dbbb021936a044e9e3 pmc_9775901.pdf bdfcde2c2c2eb7d81ab5489bb55ceb7ffbfe2604 pmc_9775901.pdf 1942c90397043280c30b537d40f854df4de530021fd066fb919083b630eff6af pmc_9775901.pdf Title: Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage—A Multicentre Study Subject: Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and H&E. Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients. Keywords: colorectal cancer; lymph node; staging; diagnosis; cytology; OSNA Author: Sherley Diaz-Mercedes, Ivan Archilla, Sara Lahoz, Maria Teresa Rodrigo-Calvo, Sandra Lopez-Prades, Jordi Tarragona, Stefania Landolfi, Angel Concha, Isidro Machado, Joan Maurel, Nuria Chic, Antoni Castells, Francesc Balaguer, Jordi Camps and Miriam Cuatrecasas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 13 11:06:33 2022 CET ModDate: Wed Dec 14 02:48:13 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2025644 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YQOTQA+VnURWPalladioL Type 1 Custom yes yes no 10 0 JAPPOA+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 KALSKC+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 AVTHRK+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 43 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 65 0 AHSHLD+CMSY10 Type 1 Builtin yes yes no 73 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 81 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 85 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 89 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 93 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 109 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 113 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 117 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 136 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 140 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 144 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 148 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 167 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 171 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 175 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 184 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 192 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 196 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 200 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 204 0 BCDJEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 211 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2023-12-06 02:35:49 CET RepresentationInformation: pmc_9775901.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-08-03 02:21:01 CEST Size: 2025644 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 423 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Patients and Inclusion Criteria Destination: subsection.2.1 Item: Title: Fresh Lymph Node Dissection and LN Analysis Destination: subsection.2.2 Item: Title: One-Step Nucleic Acid Amplification (OSNA) Assay Destination: subsection.2.3 Item: Title: CK19 Immunochemistry Destination: subsection.2.4 Item: Title: Lymph Node Pathology Reporting and pN Staging Destination: subsection.2.5 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Study Endpoints and Survival Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Clinical and Pathological Characteristics Destination: subsection.3.1 Item: Title: Patient Positive Detection Rate Is Higher with Cytology Smears and OSNA Than with H&E Destination: subsection.3.2 Item: Title: pN Upstaging with LN Cytology Smears with Respect to H&E and High Diagnostic Efficacy of Cytology Smears to Discriminate LN-Positive Patients Destination: subsection.3.3 Item: Title: The Total Tumour Load (TTL) Increases with the pN Stage Destination: subsection.3.4 Item: Title: Patients with Positive LNs Exhibit Worse Survival Outcome as Determined by Any of the Three Methods Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage A Multicentre Study Author: Sherley Diaz-Mercedes, Ivan Archilla, Sara Lahoz, Maria Teresa Rodrigo-Calvo, Sandra Lopez-Prades, Jordi Tarragona, Stefania Landolfi, Angel Concha, Isidro Machado, Joan Maurel, Nuria Chic, Antoni Castells, Francesc Balaguer, Jordi Camps and Miriam Cuatrecasas Subject: Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and H&E. Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients. 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