image: Figure 1. Research flowchart. This study screened a total of 995 patients, and ultimately determined that 397 patients met the inclusion criteria. According to whether the caudate lobe of the liver was resected, propensity score matching (PSM) was performed at a ratio of 1:1, successfully constructing two baseline-balanced study groups, each containing 146 patients.
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Hilar cholangiocarcinoma (HCCA) is the most prevalent malignant tumor of the biliary tract, with a global incidence of 4.8 per 100,000 annually and an estimated 5-year overall survival (OS) rate of 20-50%. Surgical resection is an important strategy for the treatment of hilar cholangiocarcinoma, the value of caudate lobe resection (CLR) has long been debated.
The shift to routine caudate lobectomy began when several Japanese research teams reported that the procedure improved negative margin resection rates, reduced local recurrence rates, and extended overall survival. Subsequently, a team of researchers in the United States and Europe found similar trends through retrospective analysis. Nowadays, the routine resection of hepatic caudate lobe has become the standard operation. However, hard evidence has been lacking to support this view. The shortcomings of the existing research include: 1. There is selection bias. Most studies did not clearly define the surgical indications for removal or retention of caudate lobe, and surgical decisions often relied on the subjective evaluation of surgeons. This uncertainty led to bias in the selection of research objects, and the feasibility of research results was not high. 2. Defects in research methods. Most of the previous studies were retrospective studies, and most of them did not use Propensity Score Matching (PSM) to control confounding factors, making it difficult to accurately distinguish the real impact of caudate lobotomy on surgical outcomes. 3. The purpose of the study is not clear. The primary purpose of most studies was not to define the effect of caudate lobectomy on postoperative survival, but to describe it in passing.
Faced with this controversy, the research team conducted a large-scale multicenter retrospective study. The study included 397 patients who underwent radical surgery for hilar cholangiocarcinoma at three major medical centers in China between October 2005 and April 2023 (Figure 1). As to whether the caudate lobe of the liver should be routinely resected, this study only included patients with HCCA who were determined to have no tumor invasion in the caudate lobe both preoperatively and intraoperatively. For the first time, patients were divided into the CLR group and No-CLR group through the strategy of PSM to evaluate the influence of CLR on the surgical outcome and prognosis of patients with HCCA.
The results showed that the R0 rate in the CLR group was significantly higher than that in the No-CLR group (88.4% vs 76.0%, P=0.009). However, there were no differences in OS and RFS between the CLR group and the No-CLR group before and after PSM (Figure 2). This means that routine removal of the caudate lobe does not provide a significant benefit in terms of long-term survival and recurrence. Further subgroup analysis revealed (Figure 3) that as long as the R0 margin could be achieved, regardless of whether the caudate lobe of the liver was resected or not, the survival of patients was better than those who had the caudate lobe resected but only achieved an R1 margin (R0-CLR group vs. R1-CLR group) (R0-No-CLR group vs. R1-CLR group). This once again emphasizes the importance of surgical margin status, while routine resection of the caudate lobe is not a factor in improving survival.
Multivariate analysis indicated that a higher preoperative CA19-9 level and a lower degree of tumor differentiation were independent risk factors for OS, while adjuvant therapy was a positive factor for improving OS. A lower degree of tumor differentiation and N2 staging were independent risk factors for RFS. This implies that the biological behavior of the tumor is a crucial factor influencing the prognosis of patients. It is worth noting that CLR was not an independent risk factor for postoperative survival.
For patients diagnosed with HCCA and confirmed to have no tumor invasion in the caudate lobe both before and after surgery through preoperative and postoperative assessments, routine CLR may increase the probability of achieving negative margins. However, this potential advantage is insufficient to significantly improve the patients' RFS and OS. Instead, CLR may elevate the incidence of mild complications. This conclusion provides an important reference for the surgical treatment of HCCA and reminds surgeons to carefully weigh the advantages and disadvantages when deciding whether to remove the caudate lobe of the liver that is evaluated to be free of tumor invasion before surgery. At the same time, this study also emphasizes the key role of tumor biological characteristics in determining patients' RFS and OS, highlighting the importance of comprehensive consideration of tumor biological behavior and postoperative adjuvant therapy, and pointing out the direction for the accurate treatment of subsequent HCCA. In the future, prospective randomized controlled studies with higher quality and large samples are needed to further clarify the optimal application strategy of conventional CLR in the treatment of HCCA.
Shuai Xiang and Erlei Zhang, Department of Liver Surgery, Tongji Hospital, Huazhong University of Science and Technology, are co-corresponding authors, and Ran Tao, Tong Yuan and Qi Cheng are co-first authors.
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Science China Life Sciences