Re-understanding of surgical resection techniques for liver cancer

Authors: Liu Qingguang, Song Tao, Wang Huanhuan

Source: Chinese Journal of Digestive Surgery, 2024, 23(1)

summary

Liver cancer is still a major disease that threatens the lives and health of people in mainland China. For early-stage liver cancer with good liver reserve, surgical resection remains the treatment of choice. In the past few decades, with the improvement of surgical theories, surgical skills and surgical equipment, liver cancer resection has made great progress. However, at present, there are still different understandings in the academic community on whether anatomic liver cancer resection is required, how to choose the surgical margin, the design of surgical methods under the "watershed theory" of liver, and the use of indocyanine green fluorescence imaging technology in liver cancer resection. This article comprehensively reviews the research status of the above key issues and the research progress of hepatocellular carcinoma resection, aiming to provide a reference for surgeons to choose safer and more reasonable surgical methods.

Among the many treatments for liver cancer, surgical resection remains the most important method for long-term survival. Surgical resection is still the preferred treatment for Chinese patients with stage I.a, I.b, and II.a liver cancer with good liver reserve. In recent years, with the improvement of surgical theory, surgical skills and surgical equipment, the effectiveness and safety of surgical treatment of liver cancer have been greatly improved, but there are still different understandings about the surgical implementation of liver cancer. The author reviews the research status of the above key issues, so as to provide readers with a better understanding of the research progress of liver cancer resection and the selection of safer and more reasonable surgical methods.

1. Whether anatomic liver resection can bring benefits to liver cancer patients

Hepatectomy is a well-established treatment option for liver cancer, but the need for anatomic hepatectomy remains a controversial topic. Anatomic hepatectomy refers to the surgical technique of complete resection of anatomically independent subhepatic segments, hepatic segments or combined hepatic segments, which is a liver resection based on liver segmentation, corresponding to non-anatomical hepatectomy with a certain margin along the tumor border. Makuuchi et al. proposed that anatomic hepatectomy should consist of four steps: (1) marking the hepatic segment boundary on the liver surface by staining technique or blood flow blockade. (2) Under the guidance of ultrasound, liver parenchymal resection was performed with the landmark vein of the liver segment as the boundary. (3) Fully exposed (fully exposed) veins of importance in liver sections. (4) Ligate the Glisson system near the root of the liver segment. In recent years, with the help of a full understanding of the anatomical characteristics of the internal and external vasculature and the help of liver 3D reconstruction technology, the difficulty of anatomic hepatectomy has been significantly reduced, but whether anatomic hepatectomy can bring benefits to the survival of liver cancer patients has been controversial.

The results of Moris et al. showed that compared with the non-anatomical liver resection group, patients in the anatomic liver resection group benefited from tumor-free survival at 1, 3, and 5 years after surgery, but there was no significant difference in overall survival time between the two groups. Eguchi et al. reported that anatomical liver resection was performed in patients with liver cancer, and after subgroup analysis according to tumor characteristics (tumor size, microvascular invasion), the results showed that there was a single tumor with long diameterAmong the data <of patients with liver cancer of 2 cm, 2~5 cm and >5 cm, only patients with tumor length and diameter of 2~5 cm who underwent anatomic hepatectomy had a significant improvement in tumor-free survival, and no advantage of anatomic hepatectomy was found in other groups. Shin et al. summarized the data of 5 086 patients undergoing hepatocellular carcinoma resection, including 2 496 cases undergoing anatomic hepatectomy and 2 590 cases undergoing non-anatomical hepatectomy, and the results showed that there was no significant difference in the 1-year overall survival rate between the anatomical hepatectomy group and the non-anatomical hepatectomy group, while the 3-year and 5-year overall survival rates of the anatomic hepatectomy group were better than those of the non-anatomical hepatectomy group. The 5-year recurrence-free survival rate was significantly better than that of the non-anatomical hepatectomy group, and the intrahepatic local recurrence rate and multiple recurrence rate of the anatomic hepatectomy group were lower than those of the non-anatomical hepatectomy group.

Previous studies have shown that the 2-, 3-, and 5-year recurrence-free survival rates of patients with liver cancer with malignant biological behaviors (portal venous dissemination, microvascular invasion) undergoing anatomic hepatectomy are significantly better than those of non-anatomical hepatectomy. The above results show that patients with liver cancer can benefit clinically from anatomic liver resection, patients who undergo anatomic liver resection can achieve longer tumor-free survival, and some patients can also benefit from overall survival. Therefore, in the Chinese Expert Consensus on Laparoscopic Hepatectomy for the Treatment of Hepatocellular Carcinoma (2020 Edition), it is pointed out that when conditions permit (strong comprehensive surgical ability, tumor length and diameter of 2~5 cm, unclear boundary, preoperative judgment of the possibility of vascular invasion, good liver texture and general condition, etc.), laparoscopic anatomical hepatectomy should be preferred. Hepatic segment and combined hepatic segment resection, tumor-bearing portal vein basin subhepatic segment resection and hepatic vein drainage area resection, etc. At the same time, the 2018 European Society for the Study of the Liver Clinical Practice Guidelines for Hepatocellular Carcinoma also clearly pointed out that based on the available evidence, anatomic and non-anatomical liver resection are still considered to be the surgical options for patients with resectable liver cancer.

The author believes that the reason for the inconsistency or even contradiction of so many research conclusions in clinical practice is that many confounding factors in clinical practice, such as the differences in the epidemiological characteristics of liver cancer in different populations, the influence of different preoperative imaging sensitivities and specificities on the judgment of tumor staging, the influence of surgical skills on the quality of surgery in different studies, and the influence of different postoperative systemic treatment regimens on tumor recurrence and disease course evolution will all have an impact on the overall survival time of patients. Therefore, the only way to verify the superiority of anatomic hepatectomy versus non-anatomical hepatectomy in the treatment of liver cancer is to verify the advantages and disadvantages of anatomic hepatectomy and non-anatomical hepatectomy in the treatment of liver cancer.

2. How to choose the surgical margin

Regardless of anatomic or non-anatomical hepatectomy, ensuring proper and safe margins is of great clinical significance for the prognosis of liver cancer patients, and studies at home and abroad have found that ensuring the width of the surgical margins of liver resection is of great significance for reducing the postoperative recurrence rate and improving the survival rate. The surgical margin of liver cancer refers to the closest distance from the liver section to the tumor margin at the time of liver resection. The margins are divided into R0, R1 and R2. The basic principles of liver cancer resection mainly include two aspects: (1) completeness, that is, complete resection of the tumor, so that there is no residual tumor at the resection margin. (2) Safety, that is, to retain sufficient functional liver tissue (with good blood supply and normal blood reflux and bile secretion and excretion) to meet the needs of postoperative liver function compensation, and to reduce the incidence of surgical complications and mortality as much as possible.

The width of the surgical margin is a key link to ensure the completeness and safety of tumor resection. From the perspective of thoroughness of radical liver cancer resection, the wider the margin, the better, but because most liver cancer patients in mainland China have liver cirrhosis or chronic liver disease, if the margin width is too large and too much tumor-free liver tissue is removed, it is difficult for liver function to compensate. This significantly increases the risk of surgery and the risk of postoperative liver failure, while excessive narrow margins may not achieve a radical cure, and the remaining liver is prone to small residual cancer. The results of Lin et al. showed that the 1-, 3-, and 5-year overall survival rates and tumor-free survival rates of patients with liver margins ≥ 1 cm from the tumor boundary were better than those with < 1 cm from the tumor border.

Most scholars recommend that the resection margin of liver cancer resection should be ≥ 1 cm from the tumor border, and some scholars have proposed that 1, 2, and 5 cm are the best cut-off values to distinguish the prognosis of early liver cancer. However, due to the particularity of liver anatomy, liver disease background, tumor biological behavior, etc., there is no complete clinical consensus on how far the surgical margin is from the tumor lesion to completely resect the micrometastases in the pericancerous liver tissue to achieve the effect of R0 resection, as well as the pathological criteria for R0 and its exact relationship with postoperative recurrence. According to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition), the surgical margin of the liver ≥ 1 cm away from the tumor boundary can be regarded as radical resection, and if the surgical margin is < 1 cm from the tumor border, there is no residual tumor cells in the histopathological examination of the resected liver section, which is more in line with the current clinical work of liver cancer, but requires the close cooperation and support of pathologists. Therefore, the selection of surgical margins needs to be more individualized, especially focusing on tumor factors (tumor size, capsule integrity, microvascular invasion, etc.) and surgical methods.

The results of Zhou et al. showed that very early hepatocellular carcinoma (single hepatocellular carcinoma with a tumor diameter of < 2 cm) had a prognostic advantage regardless of anatomic liver resection or non-anatomic liver resection, for patients with hepatocellular carcinoma with a tumor diameter of 2~5 cm, wide margin resection had a survival advantage, and for patients with large hepatocellular carcinoma (tumor length diameter > 5 cm), there was no significant difference in the prognosis of patients with wide margins and surgical methods.

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Re-understanding of surgical resection techniques for liver cancer