Fabio Bagante1, Thuy Tran2, Gaya Spolverato3, Andrea Ruzzenente4, Stefan Buttner5, Cecilia G Ethun6, Bas Groot Koerkamp7, Simone Conci4, Kamran Idrees8, Chelsea A Isom8, Ryan C Fields9, Bradley Krasnick9, Sharon M Weber10, Ahmed Salem10, Robert C G Martin11, Charles Scoggins11, Perry Shen12, Harveshp D Mogal12, Carl Schmidt13, Eliza Beal13, Ioannis Hatzaras14, Gerardo Vitiello14, Jan N M IJzermans7, Shishir K Maithel6, George Poultsides2, Alfredo Guglielmi4, Timothy M Pawlik15. 1. Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD; Department of Surgery, University of Verona, Verona, Italy. 2. Department of Surgery, Stanford University Medical Center, Stanford, CA. 3. Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD. 4. Department of Surgery, University of Verona, Verona, Italy. 5. Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD; Department of Surgery, Erasmus University, Rotterdam, the Netherlands. 6. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA. 7. Department of Surgery, Erasmus University, Rotterdam, the Netherlands. 8. Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN. 9. Department of Surgery, Washington University School of Medicine, St Louis, MO. 10. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI. 11. Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY. 12. Department of Surgery, Wake Forest University, Winston-Salem, NC. 13. Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH. 14. Department of Surgery, New York University, New York, NY. 15. Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD. Electronic address: tpawlik1@jhmi.edu.
Abstract
BACKGROUND: The role of routine lymphadenectomy for perihilar cholangiocarcinoma is still controversial and no study has defined the minimum number of lymph nodes examined (TNLE). We sought to assess the prognostic performance of American Joint Committee on Cancer/Union Internationale Contre le Cancer (7(th) edition) N stage, lymph node ratio, and log odds (LODDS; logarithm of the ratio between metastatic and nonmetastatic nodes) in patients with perihilar cholangiocarcinoma and identify the optimal TNLE to accurately stage patients. METHODS: A multi-institutional database was queried to identify 437 patients who underwent hepatectomy for perihilar cholangiocarcinoma between 1995 and 2014. The prognostic abilities of the lymph node staging systems were assessed using the Harrell's c-index. A Bayesian model was developed to identify the minimum TNLE. RESULTS: One hundred and fifty-eight (36.2%) patients had lymph node metastasis. Median TNLE was 3 (interquartile range, 1 to 7). The LODDS had a slightly better prognostic performance than lymph node ratio and American Joint Committee on Cancer, in particular among patients with <4 TNLE (c-index = 0.568). For 2 TNLE, the Bayesian model showed a poor discriminatory ability to distinguish patients with favorable and poor prognosis. When TNLE was >2, the hazard ratio for N1 patients was statistically significant and the hazard ratio for N1 patients increased from 1.51 with 4 TNLE to 2.10 with 10 TNLE. Although the 5-year overall survival of N1 patients was only slightly affected by TNLE, the 5-year overall survival of N0 patients increased significantly with TNLE. CONCLUSIONS: Perihilar cholangiocarcinoma patients undergoing radical resection should ideally have at least 4 lymph nodes harvested to be accurately staged. In addition, although LODDS performed better at determining prognosis among patients with <4 TNLE, both lymph node ratio and LODDS outperformed compared with American Joint Committee on Cancer N stage among patients with ≥4 TNLE.
BACKGROUND: The role of routine lymphadenectomy for perihilar cholangiocarcinoma is still controversial and no study has defined the minimum number of lymph nodes examined (TNLE). We sought to assess the prognostic performance of American Joint Committee on Cancer/Union Internationale Contre le Cancer (7(th) edition) N stage, lymph node ratio, and log odds (LODDS; logarithm of the ratio between metastatic and nonmetastatic nodes) in patients with perihilar cholangiocarcinoma and identify the optimal TNLE to accurately stage patients. METHODS: A multi-institutional database was queried to identify 437 patients who underwent hepatectomy for perihilar cholangiocarcinoma between 1995 and 2014. The prognostic abilities of the lymph node staging systems were assessed using the Harrell's c-index. A Bayesian model was developed to identify the minimum TNLE. RESULTS: One hundred and fifty-eight (36.2%) patients had lymph node metastasis. Median TNLE was 3 (interquartile range, 1 to 7). The LODDS had a slightly better prognostic performance than lymph node ratio and American Joint Committee on Cancer, in particular among patients with <4 TNLE (c-index = 0.568). For 2 TNLE, the Bayesian model showed a poor discriminatory ability to distinguish patients with favorable and poor prognosis. When TNLE was >2, the hazard ratio for N1 patients was statistically significant and the hazard ratio for N1 patients increased from 1.51 with 4 TNLE to 2.10 with 10 TNLE. Although the 5-year overall survival of N1 patients was only slightly affected by TNLE, the 5-year overall survival of N0 patients increased significantly with TNLE. CONCLUSIONS: Perihilar cholangiocarcinoma patients undergoing radical resection should ideally have at least 4 lymph nodes harvested to be accurately staged. In addition, although LODDS performed better at determining prognosis among patients with <4 TNLE, both lymph node ratio and LODDS outperformed compared with American Joint Committee on Cancer N stage among patients with ≥4 TNLE.
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