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Mohamedraed Elshami*1, Mohamed ElHag2, Wadad S. Mneimneh1, Alwalid Ammoun1, Henry J. Stitzel3, Jonathan J. Hue1, Victoria S. Wu3, Ravi Kumar Kyasaram1, John Shanahan1, John Ammori1, Jeffrey Hardacre1, Jordan M. Winter1, Lee M. Ocuin1
1Department of Surgery, UH Cleveland Medical Center, Cleveland, OH; 2Cleveland Clinic, Cleveland, OH; 3Case Western Reserve University, Cleveland, OH


Long-term survival in patients with localized pancreatic adenocarcinoma (PDAC) or ampullary adenocarcinoma (AA) who undergo resection is rare, even in lymph node (LN)-negative disease. We aimed to assess the frequency of occult metastases (OM) in patients with resected PDAC or AA discovered with a detailed pathologic examination technique on LNs previously considered negative with conventional analysis. We also examined the association between OM and overall survival (OS).


Patients with LN-negative disease on conventional pathologic analysis following resection of PDAC or AA from 2010 to 2020 were identified from our institutional database, and those with available tissue for re-analysis were included. LNs were selected for re-examination based on proximity to the tumor and size. Original hematoxylin & eosin slides, three 4-micron-thick sections from deeper levels, and one pan-cytokeratin (AE1/AE3/PCK26) immunostain were examined for each block. The primary outcome was the frequency of OM. The secondary outcome was OS.


A total of 598 LNs from 74 LN-negative patients (PDAC=71; AA=3) were re-examined in detail. A total of 49 patients (66.2%) underwent pancreatoduodenectomy, 17 (23.0%) underwent distal pancreatectomy/splenectomy, and 7 (10.8%) underwent total pancreatectomy. The median LN yield was 19. Sixteen patients (21.6%) had positive surgical margins, 18 (24.3%) had lymphovascular invasion, and 47 (63.5%) had perineural invasion. Twenty-six patients (35.1%) received neoadjuvant therapy and 35 (47.3%) received adjuvant chemotherapy.
On detailed LN analysis, 19 patients (25.7%) had OM. Of these, 9 OM (47.4%) were found only with immunohistochemistry but not on hematoxylin & eosin staining. The number of positive lymph nodes ranged from 1-3. On multivariable analysis, no clinicodemographic or pathologic factors were associated with OM.
The proportion of OM was 10.5% for patients with operative LN yields of <10 LNs, 42.0% for 10-19 LNs, 37.0% for 20-29 LNs, and 10.5% for ≥30 LNs. On conventional pathologic analysis, 3 patients (15.8%) had stage IA disease, 9 patients (26.5%) had stage IB disease, and 7 patients (36.8%) had stage IIA disease, all upstaged to stage IIB on detailed LN analysis.
On survival analysis, patients with OM had an associated decrease in OS as compared to those without OM (median OS: 22.3 vs. 50.5 months; HR=3.86, 95% CI: 1.53-9.78; Figure).


There is a high discordance rate between conventional and detailed LN pathologic analysis in resected PDAC and AA. The presence of OM is associated with worse OS. The high rate of occult nodal disease may in part explain poor survival outcomes in patients with node-negative disease.

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