Prospective randomized study comparing sentinel lymph node evaluation with standard pathologic evaluation for the staging of colon carcinoma: results from the United States Military Cancer Institute Clinical Trials Group Study GI-01 - PubMed (original) (raw)
Randomized Controlled Trial
. 2007 Jun;245(6):846-57.
doi: 10.1097/01.sla.0000256390.13550.26.
Aviram Nissan, Mladjan Protic, Carol F Adair, Diana Prus, Slavica Usaj, Robin S Howard, Dragan Radovanovic, Milan Breberina, Craig D Shriver, Ronit Grinbaum, Jeffery M Nelson, Tommy A Brown, Herbert R Freund, John F Potter, Tamar Peretz, George E Peoples
Affiliations
- PMID: 17522508
- PMCID: PMC1876962
- DOI: 10.1097/01.sla.0000256390.13550.26
Randomized Controlled Trial
Prospective randomized study comparing sentinel lymph node evaluation with standard pathologic evaluation for the staging of colon carcinoma: results from the United States Military Cancer Institute Clinical Trials Group Study GI-01
Alexander Stojadinovic et al. Ann Surg. 2007 Jun.
Abstract
Background: The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial.
Purpose: This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer.
Patients and methods: Between August 2002 and April 2006 we randomly assigned 161 patients with stage I-III colon cancer to standard histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1% isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with standard histopathology. SLN-positive disease was defined as individual tumor cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC. Primary end point was the rate of nodal upstaging.
Results: Significant nodal upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%, P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no statistically significant difference in node-positive rate was apparent between the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56) nodal upstaging was identified by evaluation of H&E stained step sections of SLNs among study arm patients who would have otherwise been staged node-negative (N0) by conventional pathologic assessment alone.
Conclusion: SLN mapping, step sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease and improves staging in patients with resectable colon cancer. A prospective trial is ongoing to determine the clinical significance of colon cancer micrometastasis in sentinel lymph nodes.
Figures
FIGURE 1. False-positive IHC staining in sentinel lymph nodes. A, H&E stained section of SLN in a patient that underwent biopsy of colon adenocarcinoma; typical postbiopsy changes of giant cells (arrow), and hemosiderin-laden histiocytes (circles). B, cytokeratin IHC section demonstrating extraneous matter and transferred tumor cells (arrow), knife carry-over effect. C, immunohistochemical endothelial cell staining (arrow). D, characteristic positive IHC staining of endogenous peroxidase-rich granular mast cells. E, positively staining mesothelium (circle) in omental fat fragment adherent to SLN on IHC. F, typical histologic appearance of nodal pigmented macrophages (circle).
FIGURE 2. Flow of participants randomized to conventional nodal histopathology and sentinel lymph node mapping and targeted pathologic assessment for colon adenocarcinoma.
FIGURE 3. Distribution of nodal disease according to type. Nodal upstaging occurred in 10.7% (6/56) by evaluation of H&E stained step sections of SLNs alone in patients randomized to SLN mapping and targeted pathologic assessment. LN, lymph node; SLN, sentinel lymph node; H&E, hematoxylin & eosin; IHC, immunohistochemistry; FN, false-negative.
FIGURE 4. Volume of disease in sentinel nodes demonstrating cytoplasmic or membranous staining in morphologically malignant cells. A, isolated tumor cell. B and C, isolated tumor cells. D, tumor cell clusters, 0.10 mm in size. E, micrometastasis 0.57 mm in size. F, macrometastasis (>2 mm in size) on H&E stained section of SLN.
Comment in
- Close collaboration between surgeon and pathologist is essential for accurate staging of early colon cancer.
Bilchik AJ, Compton C. Bilchik AJ, et al. Ann Surg. 2007 Jun;245(6):864-6. doi: 10.1097/SLA.0b013e31805d07e3. Ann Surg. 2007. PMID: 17522510 Free PMC article. No abstract available. - Alternative perspective on the rationale for lymphatic mapping for sentinel node identification in colon cancer.
Cahill RA. Cahill RA. Ann Surg. 2008 May;247(5):901-2; author reply 902-4. doi: 10.1097/SLA.0b013e31816ffad1. Ann Surg. 2008. PMID: 18438132 No abstract available.
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