As far as we know, this is the first study designed to examine risk factors for hyperamylasemia during the laparoscopic surgery with carbon dioxide pneumoperitoneum for colorectal cancer at a single facility, which involves more than 300 patients. Our team recorded and analyzed not only reported possible risk factors (the method of operation(17), the method of anesthesia(18), etc.) but also several original potential factors. It is reported that the incidence of hyperamylasemia in abdominal surgery with open operation ranges from 9% to 25%(18-22), especially 19%(17) in colonic surgery, while the incidence of hyperamylasemia in laparoscopic Roux-en-Y gastric bypass surgery is 71%(23). However, we couldn’t find related reports from open operation in the past two decades, or any more reports from laparoscopic surgery. In our study, the incidence of hyperamylasemia was relatively high (36.84%, 140 of 380 patients), postoperative serum amylase increased mostly transiently, 97.86% (137 of 140 patients) of patients returned to normal condition within 3 days and 0.71% (1 of 140 patients) of patients recovered within 5 days, others recovered within 7 days. The results of transiently elevated amylase are similar to the report from Morrissey’ team (18). Two patients with hyperamylasemia progressed to acute pancreatitis and cured under appropriate and timely treatment and 138 patients showed asymptomatic hyperamylasemia. We analyzed that it may be related to the self-repair of pancreas. Takaori et al.(24) think that the initial stage of pancreatic tissue’s damage is a reversible process and a lesser degree of inflammation can be restored by its own compensatory function, acute pancreatitis develops only when necrotic lesions that are severe enough to irreversibly affect pancreas growth and development. We guess that it is also the reason why hyperamylasemia does not necessarily accompany acute pancreatitis. As for hyperamylasemia, on the one hand, it may be due to damage to the pancreatic tissue during surgery, and on the other hand, it probably because the application of carbon dioxide pneumoperitoneum affects the microcirculation of the pancreas.
The results of our study show that the method of operation is an independent risk factor for postoperative hyperamylasemia. The mechanism may be during the operation of laparoscopic radical resection for rectal cancer, also known as Miles Operation, doctors need to remove a wide range of tissues and need to make sputum at the colon, which causes unintentional excessive pulling of the pancreas or accidental damage to the pancreas. Serum amylase increases after abdominal surgery is mainly caused by pancreatic tissue injury, especially the upper position of surgery, in which may directly damage pancreas, the incidence of hyperamylasemia is significantly increased(25). Baniel et al. also think direct pancreatic trauma with retractors may be blamed(26). To confirm this view, we reviewed recent reports of laparoscopic cholecystectomy, in which is much closer to pancreas. It does have a high incidence of hyperamylasemia during laparoscopic cholecystectomy ranging from 10% to 45%(27-30). Compared with our study, the incidence is obviously lower in the reports from Yong Fan et al.(10%, 6 of 60 patients)(30) and Ming Guo Tian et al.(12%, 4 of 33 patients)(29). However, in these two studies, the number of total cases was only 33 or 60, such a small sample size may be the key to the low incidence of hyperamylasemia.
CO2 pneumoperitoneum during laparoscopic surgery may have a significant effect on organs, especially intra-abdominal organ function, which may be the main influencing factor of hyperamylasemia in laparoscopic surgery(8-13). The results of this study show that longer duration of pneumoperitoneum can significantly increase the incidence of postoperative hyperamylasemia. Too high intra-abdominal pressure, caused by CO2 pneumoperitoneum, can oppress intraperitoneal blood vessels, especially the veins, to reduce blood perfusion of abdominal organs, while pancreatic and other substantive organs more easily affected(31, 32). The pancreas has a unique microcirculation structure, pancreatic lobules supplied by the independent lobular artery and lack of collateral circulation, which resulting in lower compensatory capacity for ischemia and prone to ischemia and ischemia-reperfusion injury(24, 33). This is an important factor in pancreatic injury. Takaori et al. analyzed that high intra-abdominal pressure may press the bile duct and the main pancreatic duct, causing the deposition of pancreatic juice and even countercurrent, which result in the damage with pancreatic tissue(34). Thus, we suspect that the incidence of hyperamylasemia in laparoscopic surgery (37%) is higher than that in open surgery (9 to 25%(18-22)) due to the large pressure from pneumoperitoneum. Unfortunately, in this study, we recorded the pressure of pneumoperitoneal in all cases, but the data were severely biased and unevenly distributed, leading us to not further explore the relationship between the pressure of pneumoperitoneum and hyperamylasemia. It is reasonable to speculate that information bias or too few cases cause such a result. It may also be explained that just when a certain pressure of pneumoperitoneum reaches a suitable time, the degree of pancreatic injury would vary with pressure. As for intraoperative blood loss, which is an important cause for hyperamylasemia, this is easier to explain. The more blood loss, the smaller blood supply of pancreatic tissue and the more likely to result in ischemic injury.
We additionally investigated some biochemical indicators that could reflect the condition of the patients’ body, such as hemoglobin, albumin, etc., but did not find a link between them and hyperamylasemia. It is very likely that the degree of change of these indicators before and after surgery is related to hyperamylasemia, and we didn’t record the values of these indicators after surgery. We plan to focus on this in future studies. Similarly, our result is consistent with the result of Morrissey et al.(18) that there is no correlation between the method of anesthesia and hyperamylasemia. In contrast, previous reports mentioned no adverse effects on the outcome of patients with hyperamylasemia(17), our conclusion also verified this view in short-term postoperative complications (χ2 = 14.298, P value = 0.112), while patients in hyperamylasemia group are more susceptible to infectious complications (χ2 = 3.937, P value = 0.047, OR = 2.283). We suspect that the sample size of our study is still insufficient, which also has to attract the attention of all medical workers.
By comparing the hospital cost and postoperative hospital stay of patients from two groups, it is easy to find that hyperamylasemia could not cause the patients’ postoperative hospital stay to prolong (Hyperamylasemia group: Normal group = 8.76 d ± 5.751:7.81 d ± 2.716, P value = 0.066), which might be related to the patient with asymptomatic hyperamylasemia needing a certain amount of time to complete the self-repair of pancreas, but this has not exceeded the sustainable level of self-repairing in patient’s pancreas. Specifically, if reach a level higher than pancreatic self-repairing ability, the postoperative hospital stay would be expected to prolong. As for the hospital cost, there was no statistically significant difference (Hyperamylasemia group: Normal group = 53180.0 yuan ± 15669.9: 51646.5 yuan ± 12819.3, P value = 0.301). Our team speculated that this is most likely because asymptomatic hyperamylasemia did not attract enough attention of medical staff resulting that they did nothing for these patients. Although the data demonstrate that there is no difference in hospital cost, patients could not benefit from it, after all, a transient increase in serum amylase might impose a certain burden on pancreas. When medical staff pays enough attention to asymptomatic hyperamylasemia, how the patient’s hospital cost change, our team plans to follow up on this aspect. From the perspective of health economics and patient’s satisfaction, doctors and nurses should pay attention to asymptomatic hyperamylasemia.
Not only that, but we also plan to design a series of hyperamylasemia diagnostic management system, including improve the nomogram scoring system that can be used to determine hyperamylasemia in early postoperative period, and postoperative management procedures for patients with hyperamylasemia to improve their living conditions and rationally optimize the allocation of medical resources.