Intrahepatic cholangiocarcinoma
- 1. Journal club Dr Sujan Shrestha MCh, First Year
- 2. Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis Title
- 3. Impact factor: 9.203 (2018) Published on January 2020
- 4. First Affiliated Hospital of Xi’an Jiaotong University of China Xu-Feng Zhang, MD, PhD Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering
- 5. Introduction Tumors of the biliary system can be anatomically subdivided into 4 groups: • Intrahepatic cholangiocarcinoma (ICC), • Perihilar cholangiocarcinoma, • Distal cholangiocarcinoma, • Gallbladder carcinoma.
- 6. ICC accounts for 10%–15% of all primary liver cancers and represents around 20% of biliary tract cancer. 5-year survival after curative-intent resection of ICC was approximately 20% to 30% among patients treated at high-volume centers. Introduction Aljiffry M,et al. J Am Coll Surg. 2009. Spolverato G, et al.. Ann Surg Oncol. 2016.
- 7. Introduction • Lymph node metastasis (LNM) has been one of the strongest predictors of poor outcome among patients undergoing curative-intent resection for cholangiocarcinoma. • To date, the prognosis of patients relative to the number of LNM has not been clearly defined among patients undergoing curative-intent resection of ICC. Rizvi S, Gores GJ. Gastroenterology. 2013
- 8. Introduction INTRAHEPATIC CHOLANGIOCARCINOMA SIGNIFICANT NODE DISEASE NO SUSPICIOUS NODE SYSTEMATIC LYMPHNODE DISSECTION PROPHYLACTIC LYMPHNODE DISSECTION DOES LND IMPROVES SURVIVAL? OR ITS JUST AN OVERSURGERY DOES LND IMPROVES SURVIVAL AND REDUCES LOCAL RECURRANCES OR ITS JUST AN OVERSURGERY • SIZE • LOCATION • TYPES
- 9. DEEP LYMPHATIC SYSTEM • PERIPORTAL • VENOUS Yuji Morine, et, al. J Gastroenterol (2015)
- 10. SUPERFICIAL LYMPHATIC SYSTEM • CONVEX SURFACE • INFERIOR SURFACE Yuji Morine, et, al. J Gastroenterol (2015)
- 11. Yuji Morine, et, al. J Gastroenterol (2015) SUPERFICIAL LYMPHATIC SYSTEM • CONVEX SURFACE • INFERIOR SURFACE
- 12. Summary of ‘‘pro’’ opinions for lymph node dissection
- 13. Summary of ‘‘con’’ opinions for lymph node dissection
- 14. Background: The objective of this meta-analysis was to evaluate the effectiveness and safety of lymph node dissection (LND) in patients with intrahepatic cholangiocarcinoma (ICC). January 2000 to January 2018 13 studies including 1377 patients were eligible. There were no significant differences in overall survival (OS) (HR 1.13, 95% CI 0.94–1.36; P = 0.20), disease-free survival (DFS) (HR 1.23, 95% CI 0.94–1.60; P = 0.13), or recurrence (OR 1.39, 95% CI 0.90–2.15; P = 0.14) between LND + group and LND-groupPostoperative morbidity was significantly higher in the LND + group (OR 2.67, 95% CI 1.74–4.10; P < 0.001). Conclusions: LND does not seem to positively affect overall survival and is associated with increased post-operative morbidity.
- 15. • The National Cancer Data Base (NCDB) was queried for patients who underwent major hepatectomy for ICC between 1998 and 2011. • Of 849 patients, 357 (42%) did not undergo lymphadenectomy • 160 patients with positive lymph nodes The median survival for lymph node negative patients was 37 months versus 15 months for lymph node positive patients. In lymph node positive patients, poorer survival was associated with not receiving chemotherapy (HR 1.83, p = 0.003), tumor size > 5 cm (p = 0.029), and older age (p < 0.0001). Conclusions: Overall survival in patients with lymph node metastases from ICC is poor. Adjuvant therapy was associated with a longer survival in lymph node positive patients, although prospective data are needed. Routine lymphadenectomy should be strongly considered to provide prognostic information and guidance for adjuvant therapy
- 18. Moderate evidence and weak recommendation Introduction
- 20. To define the impact of the relative number and station of LNM on long-term outcomes among patients undergoing curative- intent resection of ICC. To determine the minimal number of LNs harvested for optimal staging of patients Primary outcome Secondary outcome Objective
- 21. METHODS Study Cohort and Data Collection Patients who underwent curative-intent resection (R0/R1) for ICC between November 1999 and August 2017 were identified from 15 hepatobiliary centers in North America, Europe, Australia, and Asia. Preoperative LN status was evaluated by Computed tomography (CT), Magnetic resonance imaging (MRI) and/or Positron emission tomography-CT. ‘‘Suspicious’’ or ‘‘positive’’ LNs were defined as nodes abnormally shaped or swollen
- 22. METHODS • Pathologic staging was categorized according to the 8th edition AJCC guidelines.
- 23. METHODS Lymphadenectomy (LND) was defined as nodes harvested in hepatoduodenal ligament (HDL), with or without common hepatic artery, celiac artery, hepatogastric ligament, and/or peripancreatic area. 1306 patients Exclusion criteria No data on overall survival (OS)/recurrence-free survival (RFS) (82) or LND (30), Patients who had an R2 resection (20) Ablation only (21) Patients who died within 30-days after surgery (51) 1102 patients in the multi-institutional analytic cohort.
- 24. Statistical Analysis • Continuous variables were expressed as medians with interquartile ranges (IQR) and compared with Mann-Whitney U test • Categorical variables were expressed as number and percentages and compared by Chi-squared test or Fisher exact test. • Kaplan-Meier curves were used to estimate median survival; the log-rank test was used to assess differences in OS, DSS, and RFS. • Factors associated with OS were identified using Cox regression model, whereas LNM were investigated using univariate and multivariable logistic regression models.. • A 2-tailed P value of <0.05 was considered statistically significant. • Statistical analyses were performed using SPSS version 21.0 (IBM SPSS Inc., Chicago, IL) for multi-institutional databases.
- 25. RESULTS
- 26. RESULTS
- 27. RESULTS
- 28. RESULTS
- 29. Nodal Metastasis and Long-term Survival
- 30. Nodal Metastasis and Long-term Survival
- 31. DO NO OF NODES POSITIVITY AFFECT SURVIVAL? HOW MANY NODES TO HARVEST FOR ADEQUATE PROGNOSIS? WHAT STATION NODE TO BE HARVESTED? QUESTIONS
- 32. Kaplan Meier analysis of overall survival (OS) relative to the number of lymph node metastasis (LNM).
- 33. Kaplan Meier analysis of overall survival (OS) relative to the number of lymph node metastasis (LNM).
- 34. Kaplan Meier analysis of overall survival (OS) relative to the number of lymph node metastasis (LNM).
- 35. Total Number of LN Harvested and LN Status Receiver operative characteristics (ROC) analys Total number of lymph node examined (TNLE) 6 had the highest discriminatory power relative to overall survival (OS) among patients who had 1-2 LNM and patients who had 3 LNM
- 36. Total Number of LN Harvested and LN Status Kaplan-Meier analysis of OS
- 37. Stations of LND and LNM The incidence of lymph node metastasis (LNM) among patients undergoing lymph node dissection within versus beyond station number 12
- 38. Stations of LND and LNM Kaplan-Meier analysis of OS
- 39. Stations of LND and LNM
- 40. DISCUSSION • ICC frequently metastasizes to regional LNs, which can be associated with tumor recurrence after curative-intent resection. • LNM was present in roughly 40% of ICC patients who underwent surgical resection.
- 41. • Patients with no nodal disease (N0), 1 to 2 LNM (proposed N1), and 3 or more LNM (proposed N2) had an incrementally worse OS, DSS, and RFS after curative- intent resection for ICC • Consistent with the AJCC recommendations, TNLE >6 had the greatest discriminatory power relative to OS among patients with N0, N1, and N2 status. DISCUSSION
- 42. • Location and presence of LNM at certain stations were associated with long-term outcomes • Specifically, LND of station number 12 only was associated with a lower chance of identifying nodal metastasis than LND beyond station number 12. In addition, LNM beyond station number 12 was associated with a worse OS versus LNM limited to station number 12 only. DISCUSSION
- 43. Conclusion • Standard LND of at least 6 LNs is strongly recommended and should include examination beyond station 12 • The proposed new nodal staging of N0, N1 (1 – 2 LNM), and N2 (>=3 LNM) should be considered for inclusion in the next edition of the AJCC staging manual as a way to stratify more accurately the prognosis of patients after curative-intent resection of ICC.
- 44. • Title attractive and informative • Important issue ( grey zone in IHCC) • Methodology well explained • Large no of study population ( for rare tumor) • Concluded their objectives as proposed • Proposed new N staging system for future. Critical Appraisal Strength of Study
- 45. • There may be variability in patient selection and treatment, and follow-up protocols and surveillance at the different centers. (multi- institutional study) • Detail information regarding exact stations of LNM were not present. • Subgroup analysis not done Critical Appraisal Weakness of the study Location of tumor (Rt or Lt) Type of Tumor (mass forming or periductal or mixed)
- 46. Conclusion • Routine lymph node dissection in IHCC has prognostic significance • Standard LND of at least 6 LNs is strongly recommended and should include examination beyond station 12
- 47. THANK YOU
- 48. the eighth edition of AJCC/UICC manual recommend regional LND including the HDL, inferior phrenic, and gastrohepatic LNs for left-sided ICC, and the HDL, periduodenal and peripancre- atic LNs for right-sided ICC
Editor's Notes
- #10: PERIPORTAL LYMPHATICS RUNS DOWNWARD TOWARDS THE HILUM
- #12: INFERIOR SURFACE SUPERFICIAL LYMPHATIC SYSTEM HAS SIMILAR LYMPHATIC DRAINAGE SYSTEM THAT OF PERIPORTAL SYSTEM
- #13: THERE ARE SOME STUDIES WHICH FAVOURS THE LND IN IHCC
- #14: THERE ARE ALSO STUDIES NOT IN FAVOUR OF LND IN IHCC SO THERE WAS ALWAYS DEBATE IN FOR OR AGAINST LND IN IHCC
- #15: SO I WOULD LIKE TO QUOTE SOME IMPORTANT STUDIES IN THIS PARTICULAR MATTER bile leakage, infection, and ileus
- #16: Next study was also
- #17: So what are the available guidelines
- #27: Among the 1102 patient only 603 patient underwent regional lymphadenectomy
- #29: So IHCC is divided as
- #30: This table shows the risk factors associated with OS in IHCC patient following resection with LND
- #31: POOR SURVIVAL WITH INCREASE IN T AND N STAGE WAS PRESENT IN UNIVARATE ANALYSIS BUT IN MULTIVARATE ANALYSIS N STAGES WAS SIGNIFICANTLY ASSOCIATED WITH OS
- #33: So idea is do no of node metastasis has effect in OS
- #34: There is no statical significant difference in survival between 1 or 2 node positive.
- #35: But in this curve we can see significant differences in OS between 2 nodes or more nodes mets was present So these above curves shows that no of node metastasis has impact on survivability
- #37: Particularly, among patients who had TNLE <6, OS among patients with proposed N1 and N2 disease was no different (median OS, N1 18.0 vs N2 16.0, P 1⁄4 0.134) (Fig. 3B). In contrast, among patients who had TNLE 6, OS was incrementally worse as the number of metastatic LNs increased (median OS, 0 LNM 69.8 vs 1–2 LNM 26.0 vs 3 LNM 16.0 months, all P < 0.01) (Fig. 3C).
- #38: FOR THE LND DONE WITHIN STATION 12 THE INCIDENCE OF LNM WAS AND FOR LND DONE BEYOND STATION 12 THE INCIDENCE OF LNM WAS
- #39: THE OS BETWEEN
- #40: AND SIMILARLY WHEN COMBINED WITH TNLE MORE THAN EQUAL TO 6 IT WAS ALSO STATICALLY SIGNIFICANT
- #49: TNLE impacted the chance of identifying LNM and, in turn, the stage of disease. A minimum of 4 or more nodes has been recommended for perihilar cholangiocarcinoma,18 6 or more LNs for gallbladder carcinoma,19 and 12 or more LNs for distal cholangio- carcinoma. In contrast, among patients who had nodal metastasis, the number of LND did not affect OS. As such, whereas LND itself might not improve survival, LND provides information about nodal status, and may inform intensity of postoperative surveillance, and use of adjuvant therapies