Surgical Total Clearance Versus Extrahepatic Bile Duct Preservation for Biliary Tract Malignancies: A Single-Center, Randomized, Two-Arm, Prospective Phase II Clinical Trial
When lymph node dissection of stations 12 and 13 is performed, resecting the bile duct from the superior portion of the pancreas to the confluence of the right and left hepatic ducts allows complete removal of the station 12 and 13 lymph nodes. Preserving the bile duct from the superior pancreas to the hepatic confluence, however, makes a skeletonizing dissection of the duct impossible in order to safeguard the biliary blood supply, inevitably leaving behind a small amount of periductal lymphoid tissue. This results in incomplete lymph node clearance, which may increase the risk of postoperative recurrence and reduce the R0 resection rate. This study aims to investigate the lymph node dissection approach for surgically resected cholangiocarcinoma following induction therapy, to establish criteria for evaluating surgical indications, and to provide a basis for surgical treatment strategies in patients with cholangiocarcinoma.
• Age 18 years or older, regardless of gender.
⁃ Voluntary participation with full informed consent; signed written informed consent form; good compliance.
⁃ Histologically or cytologically confirmed cholangiocarcinoma (CCA).
⁃ Gallbladder cancer or intrahepatic cholangiocarcinoma with preoperative lymph node metastasis.
⁃ No prior systemic chemotherapy, immunotherapy, targeted therapy, or local treatment for CCA (including but not limited to transarterial chemoembolization, arterial embolization, arterial infusion chemotherapy, and radioactive particle embolization).
⁃ At least one measurable lesion according to RECIST v1.1.
⁃ Child-Pugh class A liver function, and no history of hepatic encephalopathy.
⁃ Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1.
⁃ Life expectancy ≥ 12 weeks.
⁃ Adequate organ function meeting the following requirements (no blood transfusion, blood products, hematopoietic growth factors, or other medications to correct blood counts within 14 days prior to randomization):
⁃ White blood cell count ≥ 4.0 × 10⁹/L;
⁃ Absolute neutrophil count ≥ 1.5 × 10⁹/L;
⁃ Platelet count ≥ 90 × 10⁹/L;
⁃ Hemoglobin ≥ 90 g/L;
⁃ Serum albumin ≥ 30 g/L;
⁃ Serum total bilirubin ≤ 2 × upper limit of normal (ULN); any biliary obstruction must be resolved before randomization;
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;
⁃ Creatinine clearance (CrCl) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula);
⁃ International normalized ratio (INR) ≤ 2 and prothrombin time (PT) prolonged ≤ 3 seconds above the ULN.
⁃ For active hepatitis B, effective antiviral therapy (per local standard of care, e.g., entecavir or tenofovir) is required, with HBV DNA \< 2000 IU/mL or a ≥ 10-fold decrease in HBV DNA after antiviral treatment; patients must agree to continue effective anti-HBV therapy throughout the study period.
⁃ Within 7 days prior to randomization, women of childbearing potential must have a negative serum pregnancy test and agree to use effective contraception during the study treatment period and for 6 months after the last dose. In this protocol, a woman of childbearing potential is defined as a sexually mature woman who: 1) has not undergone hysterectomy or bilateral oophorectomy; 2) has not been naturally postmenopausal for at least 24 consecutive months (amenorrhea following cancer therapy does not rule out fertility) (i.e., has had menses at any time in the preceding 24 consecutive months). Male patients with female partners of childbearing potential must agree to use effective contraception during the study treatment period and for 5 months after the last dose.