Although the mortality of DP has decreased markedly over the past decades, the POPF incidence of this operation mode is still the major issue. The leaked pancreatic juice destroys the surrounding tissues, which remains the main cause of secondary complications, such as abdominal haemorrhage, pancreatic pseudocyst, sepsis, organ dysfunction and even death [1, 3, 4, 9, 10]. Our work also demonstrates that POPF clearly affects the short-term prognosis of the patients (Table 4). However, the strides in both risk prediction and prevention measures of POFP for DP have fallen behind when compared to that of fistula following pancreaticoduodenectomy [11]. The primary reason for this is that surgical complications associated with a pancreatic fistula in a DP are less complicated due to the absence of a biliary and enteric anastomosis, which did not attract enough attention from the physician, and the fact that pancreatic body and tail lesions occur less frequently than pancreatic head lesions also played a role in it [10, 12].
The increased pressure in the main pancreatic duct [13] and the necrosis of the pancreatic stump [6, 14] were thought of as two factors for pancreatic fistula formation after DP. Several studies have emphasized the management of the pancreatic remnant after DP, such as the closure techniques, including pancreatico-intestinal anastomosis [5, 6], stapler and suture [4, 14-17], main pancreatic duct ligation [4, 14, 18, 19], biologic glues [20, 21], mesh reinforcement [3, 22] and pancreatic duct stent [23-25]. However, the optimal management of the pancreatic stump following DP has still not been established [4, 6, 14-16, 18, 26]. In our work, the closure techniques also did not affect the rate of POPF. Somatostatin analogues, a type of drug widely used in pancreatic surgery, have also been shown to be ineffective in reducing the POPF in some studies [4, 21, 27-30]. In this study, the much-discussed treatment of pancreatic stump (stapler VS suture) was not found to be related to the occurrence of pancreatic fistula. Although no prospective randomised clinical trials have pointed out that mesh coverage of the pancreatic remnant may be a potential approach to reduce the occurrence of POPF in patients undergone DP [3, 22], we seldom use this mesh because of the expenses associated with it. As consensus for optimising the management strategy of the pancreatic stump remains to be reached [4], it has clinical value for screening out patients with a high risk of pancreatic fistula.
Although management of the pancreatic remnant following DP remains a popular topic, studies evaluating the risk factors for DP are lacking, and the risk factors for POPF following pancreatoduodenctomy remain to be proven for POFP after DP [3, 4, 9, 11]. To our knowledge, surgical techniques and perioperative management are essential to the outcome of surgical patients. Since various techniques for management of the pancreatic remnant have proven to be invalid for decreasing the fistula rate, particular attention should be paid to the perioperative management, which include the risk factors [9, 31].
The incidence of POPF and the length of hospital stay in this study are comparable to previous reports [17, 24]. No 30-day or 90-day mortality was seen. Several POPF risk factors of DP were identified: soft pancreatic texture, history of cardiovascular disease, DA and operative time.
The soft pancreas has been regarded as a key risk factor for POPF, especially for a pancreatoduodenctomy [32, 33]. In this cohort study, 86 cases, 23 of which developed a POPF, were classified as having soft pancreas. Statistical analysis indicated that soft pancreatic texture was an important risk factor for POPF following DP (OR: 4.23, 95% CI: 1.71-10.45, P = 0.002). Hashimoto et al. reviewed 205 consecutive cases of DPs and showed that soft pancreatic parenchyma is an independent risk factor of POPF (OR: 4.89, 95% CI: 1.42–16.77, P = 0.012) [13]. On the contrary, a polycentric, retrospective study of 2,026 cases involving 52 doctors showed that patients with soft pancreas have a higher risk of developing a POPF in univariate analysis, but not independently associated with POPF after DP [11]. This may be because they did not analyse the linear relationship of possible risk factors and study the correlations between researchers, as practices varied between the surgeons. A soft pancreas that usually contains abundant pancreatic ducts and acini is fragile and can easily be injured during the operation. The regeneration of pancreatic acini and fibrotic gland leads to a hard pancreas with impaired exocrine function. The fibrotic pancreatic tissue is believed to be less prone to pancreatic leakage. This may partly explain why patients with hard pancreas have a lower incidence of POPF after DP.
Few authors stated that preoperative hypoalbuminaemia seems to be one of the risk factors for POPF following DP [11, 26, 34]. Lower levels of albumin are believed to be more likely to result in pancreatic leakage. In contrast, there was no significant difference in the level of the preoperative albumin between the two groups in our work, nor was it in the work of Kawabata [35]. We found that patients with higher DA are more prone to develop a POPF, and statistical analysis of the DA showed a difference between these 2 groups. The result (OR: 6.41, 95% CI: 2.40-17.08, P < 0.001) indicated that DA is an independent risk factor of POPF. Albumin, usually marked as a biomarker of nutritional status of patients, performs a number of important functions including transport drugs, contributing to the maintenance of plasma pH, plasma osmotic pressure and blood volume [36, 37]. It is also known that albumin can provide nutrition and energy to the fast-growing tissues, reduce the inflammatory response and stimulate repair or remodelling, such as wound healing [37, 38]. It remains to be proven whether exogenous albumin can reduce the risk of POPF for high-risk patients.
In this study, operation time (> 280.00 min) was independently associated with increased in the risk of POPF (OR: 4.18, 95% CI: 1.67-10.46, P = 0.002). In accordance with our result, a retrospective study showed that an operative time longer than 480.00 minutes was associated with a 4.21-fold increase in pancreatic fistula risk [1]. An analysis of 120 cases identified longer operative time was a risk factor for POPF, although not clinically significant POPF [39]. In another two studies, operative time was judged as the only notable predictor of POPF [26, 35]. Operative time is usually associated with extended resection, blood loss, inflammatory status, intraoperative hypothermia and pancreatic malignancies.
Aside from soft pancreatic texture, operating time and DA, cardiovascular disease also has an important effect on POPF. To our knowledge, this is the first study which identifies the cardiovascular disease as independent predictors for POPF after DP. In this study, 62 cases had a history of cardiovascular disease, 29.03% of which developed into a POPF, and multivariate analysis showed that it was associated with pancreatic fistula risk (OR:5.05, 95% CI: 1.97-13.01, P = 0.002). Cardiovascular disease, manifesting as atherosclerosis and ischaemia, is not conducive to neoangiogenesis and wound-healing [40].
The diameter of main pancreatic duct has been considered to be a key risk factor for POPF after pancreaticoduodenectomy [32, 33]. However, it has not been proven to be a risk factor for POPF after DP in our work. In practice, it is extremely rare to see a dilated downstream segment of the pancreatic duct.
In this single-centre retrospective analysis, we demonstrated that DP can be performed safely with extremely low postoperative mortality. Perioperative data, including pre-, intra- and post-operative variables were considered in this analysis, which makes it more convincing. Our findings indicated that soft pancreatic texture, longer operation time, higher DA and history of cardiovascular disease are risk factors. To reduce the rate of POPF, we can shorten surgery time by a faster operation and screening the patients with high risk.
Our study has its own limitations. First, it is a retrospective study performed at a single institution; hence, we were unable to eliminate some bias, such as selection bias. Second, our sample size remains limited, which weakens the credibility of this study. In the future, a multi-centre prospective study should be carried out, and those risk factors of POPF should be externally validated.