A high incidence of POPF is still reported in pancreatic surgery despite ongoing attempts to reduce the frequency of POPF with the development of surgical techniques and devices [4–13]. The clinical nuisance of POPF is that delayed therapeutic intervention for POPF can lead to secondary complications [1–3]. This can lead to severe disease and prolonged treatment. In this study, patients with POPF showed increase in both hospital days and mortality. Furthermore, we have previously reported that in PDAC cases, the onset of POPF leads to a delay in the initiation of postoperative adjuvant chemotherapy. Thus, POPF may affect not only short-term but also long-term prognosis. Therefore, early and accurate prediction and diagnosis of POPF and the promptest possible intervention are required. However, the median time for POPF diagnosis was 7 days (range, 3–25) in this study, making early diagnosis difficult with only routine postoperative examination. We identified two predictive factors for POPF: i) the pancreas-to-muscle SIR on T1-w MRI > 1.37, and ii) D-Amy level on POD3 > 737U/L.
D-Amy levels are one of the most established predictive and diagnostic factors for POPF. Therefore, the definition of POPF according to the ISGPF offers the standard diagnosis according to the D-Amy level on POD3. In this study, D-Amy levels were also significantly correlated with POPF. There is no doubt that amylase in the drainage fluid is useful in the diagnosis of POPF, as has been reported many times [20–41]. However, the following remain somewhat unclear: (1) the optimal timing of measurement, (2) the optimal cutoff value, (3) the optimal drain placement site, and (4) whether drainage fluid concentration or total amount of amylase is more reliable. In addition, postoperative drain obstruction due to fibrin or clots and drain misalignment often occur, which can interfere with accurate D-Amy level measurements.
The nature of the pancreas itself is thought to play a profound role in the development of POPF. In particular, the texture of pancreatic parenchyma, (soft pancreas) has been reported to be an important risk factor for POPF. However, the problem is that the pancreatic texture is very subjective and cannot be quantified. To solve this problem, we previously investigated the correlation between preoperative pancreatic MRI features and the histopathological pancreatic fibrosis grade of surgical specimens (fibrosis was graded as follows: F0 = normal pancreatic parenchyma, no fibrotic changes; F1 = mild fibrosis with thickening of periductal fibrosis tissue; F2 = moderate fibrosis with marked sclerosis of interlobular septa and no evidence of architectural changes; and F3 = severe fibrosis with detection of architectural destruction) [16, 17]. We found that the pancreas-to-muscle SIR on T1-w MRI had a significantly negative correlation with the pancreatic fibrosis grade. This is because normal pancreatic parenchyma exhibits hyperintensity on T1-w MRI, as pancreatic juice is rich in glycoproteins, and the endoplasmic reticulum within the pancreatic cells contributes to the T1 shortening effect. However, the signal intensity gradually decreases with progression of pancreatic atrophy, fibrosis, interstitial edema, or fat deposition [42, 43]. In our previous study, the mean pancreas-to-muscle SIR on T1-w MRI values for F0 and F1, which correspond to soft pancreas, were 1.51 and 1.48, respectively. Furthermore, the pancreas-to-muscle SIR on T1-w MRI in the patients with POPF was significantly higher than that in patient without POPF. Based on these findings, we hypothesized that the pancreas-to-muscle SIR on T1-w MRI might be a potential biomarker for predicting POPF and calculated the cutoff value of 1.41 . Yoon et al conducted a similar study and also reported the mean pancreas-to-muscle SIR on T1-w MRI values for F0 and F1 and the cut-off value for predicting POPF were 1.51, 1.48, and 1.40, respectively . Interestingly, the calculated cut-off value for predicting POPF (1.37) in this study is very close to that in the previous studies. Furthermore, the pancreas-to-muscle SIR on T1-w MRI also showed a significant correlation with not only POPF, but also pancreatic disease, texture of pancreatic parenchyma, and D-Amy levels.
This study had some limitations. First, it was retrospective in design and undertaken at a single institution, and involved a small number of study patients. The relatively small sample size may have caused a selection bias. This limitation should be considered when evaluating our study results. A prospective, multi-centered study is needed involving a larger number of patients in the future. Second, this study was limited to DP, for which the surgical technique is relatively simple compared to pancreaticoduodenectomy (PD). In this study, no significant correlation was found between surgical-related factors, especially surgical technique (open or lap, spleen preserving or non-preserving, hand sewn or stapler) and POPF. Therefore, the pancreas-to-muscle SIR on T1-w MRI may be effective in predicting POPF after PD and gastrectomy.