Vascular variations are frequently encountered during surgery. Approximately thirty percent of these variations are aberrant left hepatic arteries originating from the left gastric artery.

To summarize the safety and feasibility of aberrant left hepatic arteries (ALHA) ligation in gastric cancer patients who underwent laparoscopic-assisted gastrectomy (LAG).

The literature search was systematically performed on databases including PubMed, Embase, and Cochrane Library. The publishing date of eligible studies was from inception to June 2021.

A total of nine studies were included according to the inclusion and exclusion criteria in this review. The variation rate of ALHA ranged from 7.00% to 20.70%, and four studies compared the differences between the ALHA ligation group and the preservation group. Only one study showed worse postoperative outcomes in the ALHA ligation group. In all the included studies, a significant difference was found between the ALHA ligation group and the preservation group in terms of postoperative liver enzymes after LAG. However, there was no significant difference in the number of retrieved lymph nodes between the two groups.

In conclusion, it is not always safe and feasible for surgeons to ligate the ALHA during LAG surgery, and it is necessary for gastric cancer patients to undergo preoperative examination to clarify the ALHA subtypes, measure the diameter of the ALHA, and determine whether the patients have chronic liver disease.

Gastric cancer (GC) is the second leading cause of cancer-related death worldwide, with 78000 patients dying every year[1-2]. Although multidisciplinary treatment, including chemotherapy, targeted therapy, and immunotherapy, has been recommended in many countries, radical gastrectomy remains the main or even the only curative therapy for GC. Radical gastrectomy is also beneficial to long-term survival[3-4].

Laparoscopic-assisted gastrectomy (LAG) has become the main surgical method for early-stage gastric cancer[5]. Although LAG has more advantages than open gastrectomy (OG), including less estimated blood loss, shorter hospital stays and fewer complications[6-7], liver dysfunction occurs more frequently after LAG. Several studies have reported that a long carbon dioxide (CO₂) exposure time caused by a difficult LAG could result in liver function alterations[8]. However, a previous study, comparing LAG with laparoscopy-assisted colectomy, found that liver dysfunction might not be caused by CO₂ pneumoperitoneum[9]. Vascular variations are frequently encountered during surgery. Variations in the anatomy of the hepatic artery are most frequently found, and approximately thirty percent of these variations are aberrant left hepatic arteries (ALHAs) originating from the left gastric artery (LGA)[10-12]. There are two main subtypes of ALHA variations: accessory LHA (acLHA) and replaced LHA type (RLHA)[10]. Radical LAG for GC is required to sever the LGA at the root level to ensure lymph node dissection, and the existing ALHA will inevitably be severed[13]. However, the ligation of ALHA may cause liver ischemia and severe postoperative complications, such as left hepatic lobe necrosis and liver dysfunction, because parts of the liver may be supplied by this artery[14-15]. There was no significant difference in surgical outcomes between the ALHA ligation group and the ALHA preservation group according to a previous study[16].

According to existing studies, there is still controversy regarding whether ALHA should be ligated during LAG surgery, and whether liver dysfunction occurs when ALHA is ligated. Therefore, the purpose of this systematic review is to summarize and assess the safety and feasibility of ALHA ligation in GC patients who underwent LAG surgery.

A total of 549 studies were screened from the databases using the keywords. Then, duplicate studies, animal related studies and unrelated studies were excluded, and according to the inclusion criteria, 58 studies were left for further review. Next, the title and abstract from all selected studies were examined for final decisions, and 40 studies were excluded. Finally, eighteen full-text were thoroughly assessed for eligibility, and nine studies remained. According to the PRISMA statement, a flowchart was made for the detailed screening process of the study (Figure 2).

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Figure 2 The flowchart of study selection.

In this study, we systematically reviewed nine published scientific studies that focused on the safety and clinical significance of ligating the ALHA during LAG.

To our knowledge, this is the first systematic review to summarize the clinical significance of preserving the ALHA during LAG in GC patients. This is the first systematic review only on GC patients to summarize the clinical significance of ligating the ALHA during LAG by comparing the postoperative complications and the number of retrieved lymph nodes in the ALHA preserved group and ALHA ligated group. In this systematic review, we found that in five studies, the researchers strongly recommended that preserving ALHA could reduce postoperative complications. In the other four studies, the researchers reported that there was no significant difference in the changes in liver function between the ALHA ligation group and the preservation group. Only in special situations should postoperative liver function be monitored, such as in patients with chronic liver disease or those with an ALHA diameter > 1.5 mm.

ALHA variations were first reported in 1764. According to a previous study that had 57 studies related to ALHA variation, the ALHA prevalence rate reached 13.52%[19]. For a clear understanding of vascular anatomic variation, patients were asked to undergo preoperative examination before surgery. The difference in preoperative examination led to various results, with prevalence of 11.16%, 15.63%, and 13.1% for abdomen computed tomography (CT), angio-CT and visceral angiography respectively[20]. Previous studies suggested that using three-dimensional CT angiography before surgery was more beneficial than using multidetector-row CT to recognize ALHA[21]. The ALHA has been categorized into ten types based on Michel’s classification according to Cirocchi et al[20]. The ALHA is primarily composed of acLHA and RLHA. It is necessary to recognize the existence of ALHA by preoperative examination before LAG surgery, because it is difficult to determine whether the anatomic structure of ALHA is normal during LGA surgery. Also, the intraoperative ligation of ALHA may lead to increased postoperative complications and prolonged hospitalization.

Based on the five types of vascular variations reported by Cirocchi et al[20], the ALHA originates from the left gastric artery to supply the left hepatic lobe directly or indirectly. For GC patients, lymph node metastasis is commonly diagnosed, and LAG is recommended as a curative treatment, according to the Japanese Classification of Gastric Carcinoma[13]. Thus, it is necessary to dissect the metastasizing lymph nodes around the tumor completely during LAG, including lymph node Stations 1, 3, and 7[22]. However, the LGA should be severed at its root level to achieve radical cure, and the ALHA, including acLHA and RLHA, should also be ligated.

When the ALHA was ligated during surgery, severe complications, such as liver ischemia and liver failure, were reported by previous studies[16,23]. In contrast, other studies indicated that preserving ALHA could increase the operation time and estimated blood loss; however, it could not increase complications[24]. In this systematic review, four studies[16,24,28-29] that compared the ALHA preservation group with the ALHA ligation group were assessed to investigate the outcomes of GC patients with ALHA during LAG. In one of the four studies, Shinohara et al[16] reported that the ALHA ligation group had a longer operation time, higher estimated blood loss, more retrieved lymph nodes and a longer postoperative hospital stay. However, the other three studies reported negative outcomes. Furthermore, the rest five studies[9,23,25-27] used different methods to determine whether to ligate ALHA. Okano et al[25] reported that ligation of ALHA would cause transient liver enzyme changes on POD1, and the surgical outcome might be related to the ALHA-fed area and the diameter of the ALHA. Huang et al[23] showed that patients with chronic liver disease (CLD) were more susceptible to tissue damage when they encountered ischemia and hypoxia than patients without CLD. Jeong GA et al[10] indicated that liver tissue primarily produces ALT, and the ALT level should be considered the gold standard for reflecting liver function changes. It was found that the ALT level increased when the ALHA was severed, but the clinical consequences of this were not significantly different. Sano et al[26] reported that ALHA ligation was an independent risk factor (P = 0.042) for increased postoperative liver enzyme in multivariate analysis, and it was feasible to preserve ALHA when dissected the lymph nodes as standard requested. Lee et al[27], in their analysis, demonstrated that 8.6% of their included patients with ALHA ligated have longer hospital stay and higher incidence of postoperative complications.

Postoperative liver enzyme variations were reported by all nine included studies. A significant transient elevation in ALT and AST enzymes was observed within POD5. In accordance with anatomic differences in the ALHA[19], the two types of ALHA can induce various degrees of liver dysfunction. The RLHA can directly provide a larger blood supply for part of the liver tissue than acLHA, which means that ischemia and hypoxia of liver tissue may be more serious in RLHA ligation than acLHA ligation. Therefore, Waki et al[24] and Ang et al[28] recommended that liver function variations should be monitored in patients, especially those with the RLHA type. Furthermore, three studies showed that regardless of the ALHA anatomic subtypes, when the ALHA has been severed in surgery, the diameter of the ALHA was related to postoperative liver enzymes elevation. Among these studies, two studies believed that when the diameter of ALHA was greater than 1.5 mm, postoperative liver damage should be monitored carefully[24,28]. The third study believed that an ALHA diameter larger than 0.5 mm should be preserved[29]. However, the nine included studies only reported that liver enzymes were elevated in the short- term after LAG, and long- term liver function changes were not reported, because liver dysfunction gradually recovered to normal levels after POD5. Although a few studies have shown that serious complications, such as liver failure, may occur after ALHA ligation[30], most studies reported transient postoperative liver enzyme elevation, which has no obvious influence on the recovery of most patients after surgery. Surgeons should pay more attention to patients with CLD because preserving ALHA in these patients could prevent postoperative liver function deterioration.

In this systematic review, although the ALHA may influence the decision of surgeons to complete a full lymph node dissection, there was no significant difference in the number of retrieved lymph nodes between the ALHA preservation and ALHA ligation groups. Therefore, it is not necessary for the surgeon to divide ALHA for the purpose of lymph node dissection in LAG unless there are obvious signs of tumor metastasis.

This current review had some limitations. First, this systematic review included nine retrospective studies with languages limited to English, and only 4 of these studies compared the ALHA-divided group with the ALHA-preserved group to analyze the relationship between ALHA variations and liver function changes in GC patients. Second, the sample size of the included studies was relatively small. Third, these nine studies lacked pliable data to implement a meta-analysis to support this research. Forth, between the initiations of this study, the included studies lacked western studies because of none of western studies could be searched based on this search strategy. Therefore, more large-scale studies and randomized controlled trials clarifying the relationship between ALHA ligation and LAG surgery in postoperative liver function variations in GC patients are needed in the future.

In conclusion, it is not always safe and feasible for surgeons to ligate the ALHA during LAG surgery. Also, it is necessary for gastric cancer patients to undergo preoperative examination, to clarify the ALHA subtypes, measure the diameter of ALHA, and determine whether the patients have CLD.