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Lymph Node Yield After Neoadjuvant Chemoradiotherapy in Rectal Cancer Specimens: A Randomized Trial Comparing Two Fixatives

Dias, Andre R., M.D., Ph.D.; Pereira, Marina Alessandra, M.Sc.; de Mello, Evandro Sobroza, M.D., Ph.D.; Nahas, Sergio Carlos, M.D., Ph.D.; Cecconello, Ivan, M.D., Ph.D.; Ribeiro, Ulysses Jr., M.D., Ph.D.

Diseases of the Colon & Rectum: August 2018 - Volume 61 - Issue 8 - p 888–896
doi: 10.1097/DCR.0000000000001097
Original Contributions: Colorectal Cancer
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BACKGROUND: It is widely reported that neoadjuvant chemoradiation reduces lymph node yield in rectal cancer specimens. Some have questioned the adequacy of finding ≥12 lymph nodes for accurate staging, and fewer nodes were correlated with good response. Others reported that low lymph node count raises the chance for understaging and correlates with worse survival. In addition, a few studies demonstrated that diligent specimen analysis increases lymph node count.

OBJECTIVE: The aim of this study was to compare Carnoy’s solution and formalin concerning lymph node yield in specimens of patients with rectal cancer after neoadjuvant chemoradiation.

DESIGN: This is a prospective randomized trial that was conducted from 2012 to 2015.

SETTINGS: This study was performed in a reference cancer center in Brazil.

PATIENTS: Patients who underwent low anterior resection with total mesorectal excision after neoadjuvant chemoradiation for rectal adenocarcinoma were included.

INTERVENTION: Rectosigmoid specimens were randomized for fixation with Carnoy’s solution or formalin.

MAIN OUTCOME MEASURES: A total of 130 specimens were randomized. After dissection, the residual fat from the formalin group was immersed in Carnoy’s solution in search for missed lymph nodes (Revision).

RESULTS: The Carnoy’s solution group had superior lymph node count (24.0 vs 16.3, p < 0.01) and fewer cases with <12 lymph nodes (6 vs 22, p = 0.001). The Revision group found lymph nodes in all cases (mean, 11.1), retrieving metastatic lymph nodes in 6 patients. It reduced the formalin cases with <12 lymph nodes from 33.8% to 4.6% and upstaged 2 patients. Tumor response to neoadjuvant chemoradiotherapy was not associated with lymph node count.

LIMITATIONS: This was a unicentric study.

CONCLUSIONS: Compared with formalin, the Carnoy’s solution increases lymph node count and reduces the cases with <12 lymph nodes. Harvested lymph nodes are missed following routine analysis and this is clinically relevant. Finding <12 lymph nodes is not a sign of good response to neoadjuvant chemoradiation ( Unique identifier: NCT02629315). See Video Abstract at

Department of Gastroenterology, Hospital das Clinicas, Cancer Institute, University of Sao Paulo Medical School, Sao Paulo, Brazil

Funding/Support: None reported.

Financial Disclosure: None reported.

Presented at the meeting of the Brazilian Congress of Coloproctology, Brazilian Society of Coloproctology, Sao Paulo, Brazil, October 8 to 11, 2016.

Correspondence: Andre R. Dias, M.D., Ph.D., Rua Melo Alves, 89. Conjunto 102, Sao Paulo, Brazil. E-mail:

© 2018 The American Society of Colon and Rectal Surgeons