Distal cholangiocarcinoma is an epithelial malignancy originating in the middle and lower segments of the common bile duct and the ampulla of Vater (1), which accounts for approximately 20%-40% of cholangiocarcinoma (2). DCC is highly malignant and has a poor prognosis. The 1-year, 3-year and 5-year OS rates are 46%, 18% and 11%, respectively (3). Old age among males and chronic biliary tract disease are potential risk factors for its occurrence (4). Lymphatic metastasis and nerve infiltration are the main modes of invasion. Pancreaticoduodenectomy is the normative and sole therapeutic method for DCC patients (5, 6). The first case of laparoscopic pancreaticoduodenectomy (LPD) was reported by Gagner et al. in 1994 (7, 8) and has been widely carried out worldwide since then. In the past two decades, LPD has been widely used to treat DCC (3). With the advancement of operative techniques and perioperative care, the postoperative survival rate of DCC patients has been significantly improved (9). However, it is still unclear whether LPD is superior to OPD in terms of short-term outcomes and long-term survival (10). Some studies suggest that LPD takes a long time, has a complicated operation and is high risk, which has high requirements for the surgical team and a high incidence of postoperative complications (11, 12). Several recent multicenter studies have shown that LPD is a secure and practical approach. In high-volume centers with sufficient surgical experience, LPD appears to be an effective alternative, which is associated with a shorter hospital stay and similar short-term morbidity and mortality to OPD. Nevertheless, despite extensive procedural expertise, the clinical benefits of LPD compared to OPD are still insignificant (13–16). However, few studies have focused on LPD and OPD in DCC, so we conducted this study to focus on the differences between LPD and OPD in DCC to help guide the surgical treatment of DCC.

DCC is highly malignant and prone to lymphatic metastasis or nerve infiltration, and the prognosis is poor (4). At present, PD is the sole feasible and effective method for the treatment of resectable DCC. To reach the purpose of radical resection, lymph nodes need to be carefully cleaned to ensure R0 resection in PD (23). With the continuous progress of surgical technology, LPD has become a routine procedure in some pancreatic centers in recent years (24). Some studies have reported that LPD has a shorter hospital stay and rapid postoperative recovery and is not inferior to OPD in short-term oncology results (25, 26). However, there are still few studies on the treatment of DCC with LPD and OPD. This study found that the LPD group achieved similar clinical outcomes in terms of surgical safety and radical effects, and the LPD group had better long-term survival than OPD.

The incidence of total complications following LPD and OPD was reported to be comparable. In the LPD group and the OPD group, the incidence of CR-POPF was 18.02% and 18.73%, respectively, while the incidence of intra-abdominal infection was 10% and 11% (15, 27). Our study indicated that the average intraoperative bleeding volume in the LPD group was less than that in the OPD group (mean, 292.67 vs. 519. 17 mL, P=0.002), and fewer intraoperative blood transfusions were required (mean, 591.67 vs. 880. 00 mL, P=0.033). This may be due to laparoscopic amplification and clearer vision; thus, the intraoperative vascular exposure could be conducted, and intraoperative bleeding could be managed more clearly and precisely. The data in this study showed that the rate of CR-POPF in the LPD group and the OPD group was 22.2% and 23.3%, respectively, and the incidence of intra-abdominal infection was 15.6% and 10.0%, respectively. There was no statistical significance (P>0.05) and similar to the results reported in the literature, indicating that LPD can achieve short-term efficacy similar to OPD for DCC.

In addition, to achieve the consequence of radical resection, R0 resection is required (23). There was no statistical significance in R0 resection between LPD and OPD (91.1% vs. 93.3%, P=0.675). It is shown that LPD and OPD can achieve similar results in R0 resection, and it is consistent with Boggi et al. ‘‘s report that the R0 resection rate of LPD for tumors can reach 73%~100%. As distal cholangiocarcinoma is prone to lymphatic metastasis, it is widely accepted that lymphatic metastasis is an independent risk factor affecting the prognosis of DCC patients (28). In this research, we also found that lymphatic metastasis was a prognostic factor for the OS of DCC patients (P<0.05). Although research has pointed out that lymphatic metastasis and harvested lymph nodes are prognostic factors for DCC (29), there are still few studies on the relationship between harvested lymph node number and the long-term survival of DCC. In our study, although the LPD group had more harvested lymph nodes in the original cohort (mean, 14.58 vs. 10.20, P=0.01), there was no statistical significance after PSM analysis (mean, 14.3 vs. 9.93, P=0.076). This reveals that the two teams are similar in technical feasibility.

Several studies have shown that LPD and OPD have similar long-term survival rates in the treatment of pancreatic and periampullary cancers (15, 27). A recently published paper showed that there was no significant difference in long-term survival between LPD and OPD in DCC (30). In contrast, our research revealed that the prognosis for LPD was improved. Comparing the potential causes of the different outcomes, although there was no statistically significant difference after PSM, LPD harvested more lymph nodes in the initial cohort, which may be worthy of further study. Second, research has demonstrated that blood transfusions have an impact on PD patients’ long-term survival after surgery (31). Our results supported this finding and showed that LPD patients receive fewer blood transfusions, which may help improve the prognosis for LPD patients.

Many studies have focused upon the adjuvant treatment of DCC (32, 33) because the tumor heterogeneity of DCC leads to poor targeted therapy for this disease. At present, the use of gemcitabine combined with platinum drugs is generally accepted internationally, and the existence of positive lymph is an indication of adjuvant therapy (34, 35). We found that adjuvant therapy was not a predictor of OS, and the proportion of postoperative adjuvant therapy in DCC patients was 34.3%, which was lower than the international average (36). The negative results might be due to the limited numbers of samples who received postoperative adjuvant therapy in the research, and multicenter studies on DCC adjuvant therapy after PD are expected.

The study still has some limitations. First, this is a single-center, small-sample retrospective study and may inevitably involve residual confounding factors. Second, because patients do not receive unified treatment, there may be disunity factors that affect the survival of patients. To provide a clearer conclusion on the LPD of DCC, a massive prospective randomized controlled trial is needed. Hopefully soon, we can conduct a multicenter randomized trial.

In summary, compared with OPD, LPD significantly reduced intraoperative bleeding volume and blood transfusion in DCC treatment and showed a similar postoperative complication rate. With better long-term survival outcomes than OPD, LPD can be a preferred surgical option for DCC patients.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by Third Affiliated Hospital of Soochow University. The patients provided their written informed consent to participate in this study.

WC and XC designed the research and revised the manuscript. XC, WC, YueZ performed the surgery with the help of their colleagues. YuwZ, GZ, DW gathered results of each patient. YueZ and HW analyzed the data. YuwZ wrote the manuscript. All authors contributed to the article and approved the submitted version.

This study was supported by Jiangsu “333” high-level talent Project (2022, 3-4-086), Changzhou Health High-level Top-notch Talent Project (2022), Changzhou Science and technology support plan for social development (No. CE20225043). Young Talent Development Plan of Changzhou Health Commission (No. CZQM2020005, No. CZQM2021002), Major Science and Technology Project of Changzhou Health Commission (ZD201906), Applied Basic Research of Changzhou Technology Bureau (CJ20190093), and Young Talent Science and Technology Project of Changzhou Health Commission (No. QN202101).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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