In the present study, we newly elucidated the insight in which 13C trioctanoin absorption (> 38.0% dose/h) were strong preoperative physiological predictor of PF after PD in not only total cohort, but also in non-PDAC patients whose pancreatic parenchyma could be soft.
13C trioctanoin breath tests have been employed on the clinical settings to evaluate the pancreatic exocrine deficiency by detecting fat malabsorption through the gut after pancreatectomies21, 22. Until now, however, there has been few studies evaluating whether preoperative exocrine function test affect the incidence of PF after PD12, 23.
To predict the development of PF preoperatively, a lot of researchers seek to find the relevant risk factors such as high BMI24, 25, fatty pancreas10, 24, 26, male27, 28 and untreated jaundice29, and also developed the way of its prediction using various imaging modalities such as CT configurations (narrow main pancreatic duct10, thick pancreatic parenchyma10, pancreatic border6, CT attenuation value30), MRI findings31, and pancreatic ultrasound elastography32, 33 et al. Even though these predictors might be clinically useful, most of these factors are strongly associated with the soft parenchymal condition, which cause a technical difficulty of anastomosis. Therefore, whether these risk factors are reproducible or not is also depending on the type of pancreato-enteral anastomosis and maturity of those procedures. On the other hands, the data obtained from 13C trioctanoin breath test is more objective and quantitative, and especially in patients with Aa > 38.0 %dose/h, the PF incidence is extremely high regardless of parenchymal condition. Previous article mentioned the recovery of the 13C-labeled trioctanoin absorption after PD positively associated with output of pancreatic enzymes such as lipase, amylase, and chymotrypsin 15. Thus, we speculated the active production of pancreatic juice might be one of the major causes of PF after PD, and considered that outcome of the present study represented this aspect. In fact, our speculation is supported by the result showing that postoperative maximum drain amylase level (U/L) is significantly higher in patients with Aa > 38.0% dose/h than that in those with Aa < 38.0 (Fig. 4).
According to the previous reports regarding the association between PF and results of pancreatic exocrine function test, several reports revealing that higher preoperative level of FE-1 was positively associated with the developments of postoperative PF12, 30. However, there has been no study revealing the association between the result of 13C-labeled trioctanoin and occurrence of PF. Therefore, to the best of our knowledge, Aa > 38.0% dose/h is considered to be first physiological quantitative predictor of PF.
Clinical application of this study is challenging, because prevention of PF is quite difficult even if risky patients were identified preoperatively. the administration of octreotide or somatostatin analogs is well-accepted pharmacological treatment with PF targeting the secretion of pancreatic juice34, 35. The effect of somatostatin analogs is to reduce the volume of fistula output, thereby potentially alleviating the PF 36. Octreotide also has been considered to reduce the volume and potency of both pancreatic exocrine secretions and hormone production 37. Since our study demonstrate that the favorable preoperative exocrine function, which in turn high output of pancreatic juice, is regarded as the risk factor of PF, administration of these drugs might become a key treatment of PF in these risky patients. However, prospective or randomized control study should be needed to show this hypothesis.
The present research has several limitations. The first is that this study included only small number of patients. The second limitation is that the present analysis was a retrospective analysis, and we could not identify the precise mechanism how favorable pancreatic exocrine function cause the PF postoperatively. Therefore, the study is regarded as only an exploratory research. Nonetheless, our study could draw significant attention to the association between PF and preoperative pancreatic exocrine function. In conclusion, favorable pancreatic exocrine function evaluated by 13C trioctanoin breath test preoperatively, is a feasible and objective predictor of PF after PD, paying attention to the development of PF in such high-risk patients.