Adequate Lymph Node Assessment for Extrahepatic Bile Duct Adenocarcinoma

Objective:To examine the importance of adequate lymph node sampling in staging of extrahepatic bile duct cancer (EHBDCA). Summary of Background Data:The American Joint Committee on Cancer staging manual (sixth edition) states that histologic examination of at least 3 lymph nodes is required for adequate N stage determination for EHBDCA. This recommendation has not been validated; however, there has been no comparative assessment of the proximal versus distal bile duct cancer. Methods:A total of 257 patients (144 hilar cholangiocarcinoma [HCCA] and 113 distal bile duct adenocarcinoma [DBDCA]) who underwent curative intent resection (1987–2007) were analyzed; patients with gallbladder cancer were excluded. Final disease staging, including lymph node status and total number of nodes examined (total lymph node count), was obtained from the final pathology report. Differences in disease-specific survival, according to nodal status, were compared using the log-rank test. R1 resections (n = 51) were excluded from this analysis. Results:Metastasis to regional lymph nodes was noted in 89 patients (34.6%) and was an independent prognostic factor of poor survival (median disease-specific survival N0 vs. N1: 53.5 vs. 19.3 months, P < 0.0001, hazard ratio = 2.1 [95% CI: 1.4–3.2]). The median total lymph node count was 6 (range: 0–42), and was significantly lower for HCCA compared with DBDCA (median = 3 [range: 0–16] vs. 12 [range: 1–42], P < 0.001, respectively). For the entire cohort, patients who underwent R0 resection and were classified as N0, based on total lymph node count <11, had a disease-specific survival that was significantly worse than that of patients classified as N0 based on total lymph node count ≥11 (52.6 ± 9.8 months vs. not reached, P = 0.008). The estimated optimal total lymph node count for HCCA differed from that of DBDCA (n = 7 vs. n = 11, respectively). Conclusions:Adequate lymph nodes assessment of EHBDCA, based on the current AJCC recommendations, results in understaging of these tumors. With respect to the optimal total lymph node count, HCCA, and DBDCA should be considered separately.

[1]  C. Ratto,et al.  Accurate lymph-node detection in colorectal specimens resected for cancer is of prognostic significance , 1999, Diseases of the colon and rectum.

[2]  M. Aljiffry,et al.  Evidence-based approach to cholangiocarcinoma: a systematic review of the current literature. , 2009, Journal of the American College of Surgeons.

[3]  M. Gonen,et al.  Extrahepatic cholangiocarcinoma: a comparison of patients with resected proximal and distal lesions. , 2008, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[4]  M. D'Angelica,et al.  Intrahepatic and Extrahepatic Biliary Cancer , 2007 .

[5]  R. Hruban,et al.  Recommendations for the Reporting of Pancreatic Specimens Containing Malignant Tumors , 1999 .

[6]  C. V. D. van de Velde,et al.  Lymph node staging standards in gastric cancer. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  F. Greene.  AJCC cancer staging handbook , 2002 .

[8]  Steven C Cunningham,et al.  Cholangiocarcinoma: Thirty-one-Year Experience With 564 Patients at a Single Institution , 2007, Annals of surgery.

[9]  P. Hermanek,et al.  Two programmes for examination of regional lymph nodes in colorectal carcinoma with regard to the new pN classification. , 1989, Pathology, research and practice.

[10]  G. Leonard,et al.  Biliary tract cancers: current concepts and controversies , 2005, Expert opinion on pharmacotherapy.

[11]  M. Brennan,et al.  Outcome of treatment for distal bile duct cancer , 1996, The British journal of surgery.

[12]  C. Compton,et al.  Impact of number of nodes retrieved on outcome in patients with rectal cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  David D. Smith,et al.  Lymph Node Dissection Impact on Staging and Survival of Extrahepatic Cholangiocarcinomas, Based on U.S. Population Data , 2007, Journal of Gastrointestinal Surgery.

[14]  Murray F. Brennan,et al.  Prognostic Nomogram for Patients Undergoing Resection for Adenocarcinoma of the Pancreas , 2004, Annals of surgery.

[15]  I. Endo,et al.  Clinical Significance of Intraoperative Bile Duct Margin Assessment for Hilar Cholangiocarcinoma , 2008, Annals of Surgical Oncology.

[16]  M. Gonen,et al.  Staging, Resectability, and Outcome in 225 Patients With Hilar Cholangiocarcinoma , 2001, Annals of surgery.

[17]  G. Veillette,et al.  Distal biliary malignancy. , 2008, The Surgical clinics of North America.

[18]  D. Gouma,et al.  Extended lymph-node dissection for gastric cancer. , 1999, The New England journal of medicine.

[19]  G. Fleuren,et al.  Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries. , 1995, Journal of Clinical Oncology.

[20]  M. Nagino,et al.  Lymph Node Metastasis from Hilar Cholangiocarcinoma: Audit of 110 Patients Who Underwent Regional and Paraaortic Node Dissection , 2001, Annals of surgery.

[21]  R. Jenkins,et al.  Proximal biliary malignancy. , 2008, The Surgical clinics of North America.

[22]  C C Compton,et al.  Updated protocol for the examination of specimens from patients with carcinomas of the colon and rectum, excluding carcinoid tumors, lymphomas, sarcomas, and tumors of the vermiform appendix: a basis for checklists. Cancer Committee. , 2000, Archives of pathology & laboratory medicine.

[23]  M. Gönen,et al.  Prognostic Significance of Pathologic Nodal Status in Patients with Resected Pancreatic Cancer , 2007, Journal of Gastrointestinal Surgery.

[24]  L. Ben-Porat,et al.  Papillary Phenotype Confers Improved Survival After Resection of Hilar Cholangiocarcinoma , 2005, Annals of surgery.

[25]  S. Kitano,et al.  Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. , 2002, Archives of surgery.

[26]  C. Heffess,et al.  Recommendations for the reporting of pancreatic specimens containing malignant tumors. The Association of Directors of Anatomic and Surgical Pathology. , 1999, American journal of clinical pathology.

[27]  D. Klimstra,et al.  Lymph Node Staging in Gastric Cancer: Is Location More Important Than Number?: An Analysis of 1,038 Patients , 2000, Annals of surgery.

[28]  F. Bosman,et al.  For patients with dukes' B (TNM stage II) colorectal carcinoma, examination of six or fewer lymph nodes is Related to poor prognosis , 1998, Cancer.

[29]  M. Huguier,et al.  [Extended lymph-node dissection for gastric cancer]. , 1999, Chirurgie; memoires de l'Academie de chirurgie.

[30]  M. Choti,et al.  Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. , 2007, Surgery.

[31]  C. Compton,et al.  Protocol for the examination of specimens removed from patients with carcinoma of the exocrine pancreas: a basis for checklists. Cancer Committee, College of American Pathologists. , 1997, Archives of pathology & laboratory medicine.

[32]  G. Fleuren,et al.  Lymph node retrieval in a randomized trial on western-type versus Japanese-type surgery in gastric cancer. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.