EJAL is a serious and potentially fatal complication after gastric surgery. It has been reported that EJAL has a mortality rate of up to 50% and is the major reason of postoperative death after surgery [13]. The present study found the incidence of EJAL was 2.6% (10/390), which was similar to a recent quality meta-analysis with 2484 gastric cancer patients that reported the incidence of AL after total gastrectomy was 2.5% [14]. Moreover, this study also found a mortality rate of 10% (1/10), which further highlights why the risk of developing EJAL should be evaluated during the perioperative period.
Identification of risk factors of EJAL helps reduce the incidence of this condition in the clinic. Previously reported risk factors have mainly included patient-, surgery-, and tumor-related factors. In the present study, the univariate analysis showed that age > 65 years (OR = 5.014, P = 0.025),alcohol consumption (OR = 5.473, P = 0.019), pulmonary insufficiency (OR = 3.866, P = 0.049), and intraoperative blood loss (OR = 5,885, P = 0.015) were risk factors associated with EJAL. The multivariate analysis revealed that only age (OR = 3.882, P = 0.043) and alcohol consumption (OR = 3.828, P = 0.043) were the independent risk factors associated with EJAL in gastric surgery.
The present study also found that EJAL was more likely to occur in patients of advanced age, which is in line with two previous studies [6, 9]. Gastric cancer occurs more frequently in older patients. Unfortunately, older patients tend to be in poorer physical and wound healing condition and often suffer from malnutrition and comorbidities, making it more difficult for them to withstand the stress of surgery and keep physiological functions in balance, thereby to a certain degree increasing the risk of anastomotic leakage. Due to the poor ability of older patients to respond to stimuli, the early clinical symptoms of anastomotic leakage might be atypical and prone to be missed or misdiagnosed; thus, more attention should be paid to EJAL in older patients. Moreover, it was worth noting that it is still a matter of controversy whether diabetes affects the incidence of anastomotic leakage. Diabetes is well known to affect wound healing, not only including surgical incisions [15] but also intestinal anastomoses [16]. Kazuhiro [7] even reported that poor preoperative diabetic control was an independent risk factor for EJAL. Interestingly, all ten patients who developed EJAL in this study did not have diabetes, and several previous reports [1, 3, 5–6, 9–10] failed to find any association between diabetes and EJAL. Therefore, the authors think that the effect of perioperative diabetic control on anastomotic leakage may have stronger impact than the diabetes itself.
Although Isozaki [3] and Sauvanet [17] successively reported that pulmonary insufficiency was not a risk factor for EJAL, Wu [18] found that respiratory disease was associated with postoperative complications after gastric surgery. Deguchi [6] further revealed that pulmonary insufficiency was an independent risk factor of EJAL. This may be explained by poor oxygen supply due to pulmonary insufficiency, combined with restricted breathing due to the pain after abdominal surgery, both of which may affect the healing process after gastric surgery. Moreover, the anastomotic leakage could aggravate impaired lung infection, and a vicious circle could develop. A high-quality randomized controlled trial by Schietroma [19] found that the risk of EJAL was 49% lower in patients who received 80% FiO2 than in those who received 30% FiO2 during and 6 h after open total gastrectomy surgery; this issue deserves further attention.
Although anastomotic leakage might be a complication driven by many factors, alcohol consumption has previously been associated with increased postoperative complications in colorectal cancer patients [20–21]. Rullier and Sorensen [22–23] reported that smoking and alcohol abuse were major risk factors for anastomotic leakage in colorectal surgery. Thomas [24] further demonstrated that an alcohol intake of more than 60 g/day was associated with an increased risk of anastomotic leakage in colorectal surgery. However, such analyses have rarely been published in studies of gastric cancer. To the best of our knowledge, this is the first study to report alcohol abuse being associated with EJAL upon gastric surgery. Alcoholism may affect the healing process and lead to impaired anastomotic integrity in various ways described below. Alcohol has been recognized as an influential factor in hemostasis, and excessive alcohol consumption may lead to increased perioperative bleeding because of bone marrow toxicity and decreased levels of fibrinogen, VII factor, and von Willebrand factor [25–27]. Cardiac insufficiency, immunosuppression, and hemostasis have also been demonstrated in symptom-free alcohol abusers with postoperative complications [28]. Therefore, preoperative use of alcohol should be identified and managed appropriately before surgical operation. Moreover, a history of alcohol consumption is an influential factor in the development of postoperative complications that clinicians should not forget. To obtain beneficial short-term reversibility of physiological impairments, 4-week alcohol abstinence prior to surgery has been advised [21]. Several studies [20–24] also revealed that smoking was a risk factor for anastomotic leakage and increased the postoperative complications upon rectal surgery. Although 40% of patients (4/10) with a history of smoking developed EJAL, this factor failed to reach statistical significance in the present study but should be further discussed in the future.
With the arrival of the “minimally invasive” era, a significant reduction of intraoperative bleeding becomes possible. Though intraoperative blood loss was not an independent risk factor in this study, the authors speculate that it should not be ignored in gastric surgery. On the one hand, extensive blood loss during operation might impair the blood supply around the anastomosis, resulting in insufficient blood supply around the anastomosis and further increasing the risk of anastomotic leakage. One the other hand, the decrease in hemoglobin resulting from extensive blood loss will weaken the oxygen-carrying capacity, thereby causing anastomotic leakage. Three previous studies [1, 6, 10] reported that longer duration of operation and combined organ resection including splenectomy or pancreatectomy were associated with anastomotic leakage, increasing the risk of morbidity. However, the present study failed to reach this conclusion, and the main reason for this may lie in staff experience and the use of optimized mechanical devices, which make the surgery faster and more secure, ultimately decreasing the incidence of anastomotic leakage.
In recent years, neoadjuvant chemotherapy has been used more frequently in the treatment of advanced gastric cancer. However, only one patient (1/78) who received neoadjuvant chemotherapy developed EJAL after surgery and did not achieve significance, which was consistent with the study of Deguchi [6]. Therefore, it might not be a risk factor of EJAL.
One of the most important findings of this study was the identification of alcohol consumption being an independent risk factor for EJAL in patients receiving surgery for gastric cancer. However, several limitations should be considered. This was a single-center and retrospective study, and although it involved no less than 390 consecutive patients, the generalizability of our conclusions might be limited. Therefore, more clinical research is necessary, especially RCTs. Another drawback is that no survival analysis was performed for this study due to inadequate 5-year follow-up data available for analysis. However, research involving survival analysis is ongoing in our unit and will also be reported in the future.