Objective To investigate the ten‑year evolution of surgical treatment for intra-hepatic cholangiocarcinoma (ICC) and improvement of prognosis in a single center.
Methods The retrospective cohort and propensity score matching (PSM) study was conducted. The clinicopatholo-gical data of 1 905 patients with ICC who were admitted to Zhongshan Hospital of Fudan University from January 2013 to December 2022 were collected. There were 1 161 males and 744 females, aged (61±10) years. All 1 905 patients underwent radical resection of liver cancer. Based on the time of admission, there were 738 cases from 2013 to 2017, and 1 167 cases from 2018 to 2022. According to the surgical approach, there were 1 639 cases in the open surgery group and 266 cases in the laparoscopic surgery group. Of 1 905 patients, 816 cases had postoperative recurrence including 656 cases of early recurrence and 160 cases of late recurrence. Observation indicators: (1) clinico-pathological characteristics of patients with ICC in different periods; (2) surgical and prognostic conditions of patients with ICC in different periods; (3) stratified analysis of surgical conditions of patients with ICC; (4) adjuvant therapy and prognosis of patients with ICC in different periods. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon rank sum test. Comparison of count data between groups was conducted using the chi‑square test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log‑rank test was used for survival analysis. PSM was done by the 1∶2 nearest neighbor matching method.
Results (1) Clinicopathological characteristics of patients with ICC in different periods: the age, cases without or with cirrhosis, cases with surgical difficulty as medium‑low difficulty or high difficulty, cases with tumor diameter ≤5 cm or >5 cm, cases with well differentiated tumor or medium‑low differentiated tumor, cases with or without lymph node dissection, cases with or without adjuvant therapy were (60±10) years, 628, 110, 373, 365, 376, 362, 283, 455, 308, 430, 329, 409 of patients who were admitted from 2013 to 2017, versus (62±10) years, 1 051, 116, 526, 641, 694, 473, 632, 535, 708, 459, 780, 387 of patients who were admitted from 2018 to 2022, respectively, showing significant differences in the above indicators between them (P<0.05). (2) Surgical and prognostic conditions of patients with ICC in different periods: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with grade Ⅰ‒Ⅲ complications of Clavien‑Dindo classification were 245 (180,320) minutes,200 (100,300) mL, 68, 178 of patients who were admitted from 2013 to 2017, versus 210 (180,300) minutes, 100 (100,300) mL, 59, 231 of patients who were admitted from 2018 to 2022, respectively, showing signifi-cant differences in the above indicators between them (P<0.05). Results of survival analysis showed that the 1‑, 3‑, 5‑year overall survival rates were 76.0%, 48.8%, 38.5% of patients who were admitted from 2013 to 2017, versus 88.2%, 61.5%, 48.9% of patients who were admitted from 2018 to 2022, respectively, showing a significant difference between them (χ²=33.784, P<0.05). Among 1 016 pati-ents with lymph node dissection, the 1‑, 3‑, 5‑year overall survival rates were 63.0%, 26.0%, 17.7% of 357 patients with positive lymph node microscopy, versus 89.0%, 62.4%, 49.8% of 659 patients with negative lymph node microscopy, respectively, showing a significant difference between them (χ²=158.136, P<0.05). The 1‑, 3‑, 5‑year recurrence‑free survival rates were 64.4%, 28.4%, 21.8% of 357 patients with positive lymph node microscopy, versus 77.3%, 51.1%, 45.6% of 659 patients with negative lymph node microscopy, respectively, showing a significant difference between them (χ²=37.397, P<0.05). The 1‑, 3‑, 5‑year overall survival rates were 89.0%, 62.4%, 49.8% of 659 patients with negative lymph node microscopy, versus 87.3%, 63.3%, 50.8% of 889 patients without lymph node dissection, respectively, showing no significant difference between them (χ²=0.261, P>0.05). The 1‑, 3‑, 5‑year recurrence‑free survival rates were 77.3%, 51.1%, 45.6% of 659 patients with negative lymph node microscopy, versus 77.1%, 56.5%, 49.7% of 889 patients without lymph node dissection, respectively, showing no significant difference between them (χ²=1.481, P>0.05). (3) Stratified analysis of surgical conditions of patients with ICC: of the 1 905 patients, 798 cases were successfully matched, including 532 cases in the open surgery group and 266 cases in the laparos-copic surgery group. The volume of intraoperative blood loss, cases with intraoperative blood trans-fusion, cases with grade Ⅰ‒Ⅲ complications of Clavien‑Dindo classification were 200 (100,300) mL, 21, 91 of patients in the open surgery group, versus 100 (50,100) mL, 2, 9 of patients in the laparos-copic surgery group, respectively, showing significant differences in the above indicators between them (P<0.05). After PSM, the 1‑, 3‑, 5‑year overall survival rates were 89.8%, 66.1%, 50.6% of patients in the open surgery group, versus 94.1%, 74.5%, 64.9% of patients in the laparoscopic surgery group, respectively, showing a significant difference between them (χ²=8.113, P<0.05). The 1‑, 3‑, 5‑year recurrence‑free survival rates were 78.4%, 53.7%, 48.3% of patients in the open surgery group, versus 85.7%, 65.7%, 61.4% of patients in the laparoscopic surgery group, respectively, showing a significant difference between them (χ²=7.851, P<0.05). (4) Adjuvant therapy and prognosis of patients with ICC in different periods: the method with the highest proportion of adjuvant therapy was traditional Chinese medicine for patients who were admitted from 2013 to 2017, and systemic therapy for patients who were admitted from 2018 to 2022. The proportion of patients receiving systemic therapy increased from 30.09%(99/629) in patients who were admitted during 2013‒2017 to 69.23%(540/780) in patients who were admitted during 2018-2022. Chemotherapy accounted for the highest proportion among systemic therapy for patients who were admitted during 2013‒2017 and 2018‒2022. For 656 early recurrence patients, the 1-, 3-, and 5-year overall survival rates were 91.0%, 44.3% and 25.5% of cases with adjuvant therapy, versus 80.8%, 32.8% and 19.7% of those without adjuvant therapy, respectively, showing a significant difference between them (χ²=10.197, P<0.05).
Conclusions Compared to patients with ICC who were admitted from 2013 to 2017, patients with ICC who were admitted from 2018 to 2022 are older, but the proportions of patients with cirrhosis, tumor diameter >5 cm or low differentiated tumor are lower. The proportions of difficulty surgery, lymph node dissection and adjuvant therapy are increased, while the operation time, cases with perioperative bleeding, blood transfusion, and postoperative complications are decreased, resulting in an improved overall survival rate. Patients undergoing lymph node metas-tasis have a poor prognosis, but patients with negative lymph node do not benefit from lymph node dissection. Patients with laparoscopic surgery have better perioperative indicators and a better prognosis compared to cases undergoing open surgery. Adjuvant therapy can improve the prognosis of patients with early recurrence.
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