lNTRODUCTlON

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 (CO) 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 COpneumoperitoneum[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.

He got plenty to run for, too, for all the hunters aimed at him, and tried to shoot him, and the dogs barked and ran after him wherever they got wind of him

MATERlALS AND METHODS

Search strategy

This systematic review was designed and performed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement[17]. This study is a systematic review of literature related to the change in postoperative liver function after gastrectomy with ligation of the ALHA. 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. We searched databases using the following keywords:“l(fā)eft hepatic artery”, “LHA”, “stomach tumor”, “stomach neoplasm”, “stomach cancer”, “cancer of stomach”, “gastric cancer” and “gastrectomy” (Table 1).

Inclusion criteria and exclusion criteria

The title and abstract of all searched articles were independently screened by two authors. All articles conforming to the inclusion and exclusion criteria were eventually included in the study. The Inclusion criteria were as follows:(1) Study type:cohort studies, case-control studies, and retrospective studies on humans; (2) English language articles published in scientific journals; (3) Full-text articles available; and (4) Articles related to this research. The exclusion criteria were as follows:review, case reports, commentaries, randomized clinical trials and conference abstracts.

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.

Data extraction

As soon as he had got into the court-yard, he moved very softly, and theladies were so much engrossed21 with counting the kisses, that all might go onfairly, that they did not perceive the Emperor. He rose on his tiptoes.

The anatomy variation of aberrant left hepatic artery

The ALHA has two primary subtypes. The first originates from the LGA in the extrahepatic area and communicates with the LHAthe accessory LHA (acLHA). In the second subtype, there is no LHA in the extrahepatic area, and an artery that emanates from the LGA communicates with the hepatic vasculature to replace the function of the LHA. This artery is referred to as the replaced LHA (RLHA). Figure 1 shows the two subtypes of ALHA in detail.

The full text of all included articles was independently screened by two researchers. Perioperative information, including the first author, publication year, country, study date, surgical procedure, simple size, vascular variation rate and main outcome, was extracted.

Quality assessment

The quality of the nine included studies was assessed by the Newcastle-Ottawa Scale[18], and the results are reported in Table 2.

The thermometer had dropped to 18 degrees below zero, but still chose to sleep in the porch as usual. In the evening, the most familiar sight to me would be stars in the sky. Though they were a mere1 sprinkle（） of twinkling dots, yet I had become so accustomed to them that their occasional absence would bring me loneliness and ennui2（） .

RESULTS

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).

The characteristics of included studies

The nine included studies all originated in Asian countries, including 4 studies in Japan, 4 studies in Κorea and 1 study in China. The year of publication ranged from 1993 to 2021. The sample size for these studies ranged from 28 to 215, with an average sample size of 135. Six studies were conducted to evaluate the safety of severing ALHA during LAG, and OG and LAG were discussed in the other three studies. According to the population characteristics of the included studies, 8 studies calculated the vascular variation rate of the simple set, and the rate ranged from 7.00% to 20.70%.

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[24] and Ang[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.

The perioperative outcomes

We extracted operative outcome data from four studies that compared the surgical outcomes of the ALHA ligation group and the ALHA preservation group. The surgical outcome reported by Shinohara[16] indicated that the operation time was significantly longer, and the estimated blood loss and the number of retrieved lymph nodes were significantly higher in the ALHA-divided group than in the ALHA-preserved group (= 0.014,= 0.005 and= 0.018, respectively). However, the surgical outcomes were not significantly different between the two groups in the other three studies. Furthermore, the surgical complications between the two groups were not significantly different in the four studies. According to these four studies, the postoperative variation of liver enzymes was used to reflect the changes in liver function, of which the variation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used as the main postoperative indicators. There were statistically significant differences in postoperative changes in liver enzymes between the ALHA-ligated group and the ALHA-preserved group on postoperative day (POD) 1, POD2, POD3, and POD5 (Table 3).

DlSCUSSlON

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[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.

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.

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[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[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[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[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[26] reported that ALHA ligation was an independent risk factor (= 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[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.

We summarized the main results of nine studies and divided their conclusions on the preservation of ALHA into two degrees of suggestions, of which the “possible preserve” was weak one, and the “preserve” was strong. Five studies suggested that it is of great necessity to preserve the ALHA to prevent postoperative liver dysfunction. However, the conclusions of other studies were that the ALHA could be ligated in appropriate situations, such as patients without chronic liver disease, an ALHA diameter less than 1.5 mm, and when more precise examinations are needed (Table 2).

Then the young man gave her his promise to make her his wife, and the girl fulfilled her part of the bargain, and food was plentiful23 on the island all through the long winter months, though he never knew how it got there

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.

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

CONCLUSlON

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.

It happened that the eldest1 wanted to go into the forest4 to hew2 wood, and before he went his mother gave him a beautiful sweet cake5 and a bottle of wine in order that he might not suffer from hunger or thirst.

One Sunday, he followed me to my car and asked me to go to lunch with him. I think we both knew we felt something special for each other before that lunch was finished. Less than a month later, he proposed. I accepted but with much fear in my heart. I was determined5 not to ever be abused again. Three years of marriage to this wonderful man has brought me immense（，） joy as he has showered me with his love, compassion6 and caring. He has become my husband, my lover, my companion, and my best friend. I have learned the difference between self-serving, abusive（，） love and the real, true, self-sacrificing kind of love. The best thing I can think to say about this big, bald（） Texan is that he enables me to find the best in myself and loves me as I am. Sometimes, love is sweeter the second time around.

ARTlCLE HlGHLlGHTS

Research background

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.

Research motivation

A previous study, comparing LAG with laparoscopy-assisted colectomy, found that liver dysfunction might not be caused by carbon dioxide pneumoperitoneum. 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.

They were taller than mortal men, and the young man had a staff in his hand with golden wings on it, and two golden serpents twisted round it, and he had wings on his cap and on his shoes

Research objectives

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.

Research methods

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.

Research results

A total of nine studies were included in this review. 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.

Research conclusions

Chasid listened with favour to his servant s suggestion, and perceiving in the valley beneath them a ruin which seemed to promise shelter they flew towards it

Research perspectives

Based on the five types of vascular variations reported by Cirocchi[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.

Prince Vivien was fully11 aware of the feeling in his favour, but being too honourable12 to wish to injure his pretty cousin, and perhaps too impatient and volatile13 to care to think seriously about anything, he suddenly took it into his head that he would go off by himself in search of adventure

Tao W and Peng D contributed equally to this work; Zhang W designed the research study; Tao W wrote the manuscript; Peng D and Cheng YX conducted data extraction; Tao W conducted figure painting; Tao W, Peng D, Cheng YX and Zhang W conducted writing review and editing; all authors read and approved the final manuscript.

Authors declare no conflict of interests for this article.

This systematic review was designed and performed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See:https://creativecommons.org/Licenses/by-nc/4.0/

China

Wei Tao 0000-0002-3149-0642; Dong Peng 0000-0003-4050-4337; Yu-Xi Cheng 0000-0002-9220-7855; Wei Zhang 0000-0002-5822-9970.

” And then he kissed her rosy mouth, played with her long waving hair, and laid his head on her heart, while she dreamed of human happiness and an immortal soul

Ma YJ

A

Ma YJ