This study’s main finding was that the CRP level on POD 3 was an independent and significant predictive factor for PIAA and CR-POPF after distal pancreatectomy. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., BMI, SFA, and VFA) were identified as predictive factors for PIAA but not for CR-POPF. The median postoperative period of PIAA formation was 9 days; PIAA patients with drainage had a higher preoperative HbA1c level, and open surgery for distal pancreatectomy was performed more frequently for PIAA patients with drainage than for those without drainage.
Intra-abdominal abscess is a surgical site infection that often occurs after gastrointestinal surgery and is occasionally the cause of postoperative mortality [13, 14]. PIAA is diagnosed when symptoms (e.g., abdominal pain and fever) and increased inflammation level according to laboratory data are noted, and CT findings, such as FC with definitive encapsulation, enhanced thick wall, or air bubbles, are observed postoperatively [14]. In this study, the definition of PIAA was mainly dependent on CT findings checked by two of three radiologists regardless of the culture of the abscess, because we did not perform percutaneous ultrasound, CT, or endoscopic ultrasound-guided interventions for all PIAA patients, and could not collect culture of PIAA. Although most procedures were not contaminated operations, and there were PIAA patients with lower drain amylase levels on PODs 1 and 3; some patients developed PIAA after removal of the prophylactic intra-abdominal drains that were inserted intraoperatively.
After distal pancreatectomy, FC is frequently observed [7], and Yoshino et al. [8] reported that FC occurred in most patients (94.5%) postoperatively and that it disappeared within 1 year in majority of these patients (77.5%). Generally, FC is insignificant; however, FC occasionally progresses to PIAA, thereby requiring conservative or progressive treatment. Most studies have focused on CR-POPF; to our knowledge, this study is the first to reveal clinical data and predictive factors for PIAA after distal pancreatectomy. We speculated that there might be another mechanism and other preventive measures against PIAA after surgery compared to POPF.
The mechanism for PIAA formation was unclear, although the occurrence of PIAA may be deeply involved with subclinical and potential leakage of pancreatic juice and the amount of intra-abdominal fat. Although the drain amylase levels on POD 1 or POD 3 were not a predictive factor for PIAA or CR-POPF in this study, subclinical and potential leakage of pancreatic juice may be accelerated by functional distal obstruction of the sphincter of the Oddi complex at the ampulla or an increase in food intake [15, 16], and this leakage later becomes evident after several PODs. Meanwhile, many surgeons believe that the amount of intra-abdominal fat tissues is an important risk factor for postoperative complications [17]. Sledzianowski et al. [2] have revealed that obesity is a risk factor for intra-abdominal morbidity after distal pancreatectomy. In this study, preoperative indices representing abdominal fat mass (i.e., BMI, SFA, and VFA) were identified as predictive factors for PIAA but not for CR-POPF. Hence, patients with CR-POPF without forming intra-abdominal abscess who had peripancreatic drainage for over 3 weeks might not have obesity or have less amount of intra-abdominal fat. Therefore, PIAA may not occur postoperatively if there are less visceral adipose tissues around the surgical site, which may be dissolved by pancreatic juice and may be the origin of surgical site infection, even if subclinical and potential leakage of pancreatic juice may continue to occur postoperatively.
Several studies have revealed that an elevated postoperative CRP level is an early indication of CR-POPF after pancreaticoduodenectomy, although there are few reports for distal pancreatectomy [6]. Our study revealed that the CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy. The CRP level on POD 3 is clinically important information, and monitoring the CRP level may help prevent PIAA formation. First, if the CRP level on POD 3 is relatively high, it may be effective to extend the duration of prophylactic intra-abdominal drainage, added during operation, for a few more days irrespective of the drain amylase level on POD 3. Meanwhile, if the CRP level on POD 3 is not high, early removal may be necessary because prolonged placement of a drain tube may result in retrograde infection [9]. Second, the elevation of CRP levels occur due to subclinical and potential POPF; thus, delaying the resumption of food intake may be practical [16]. Finally, a high CRP level suggest unspecific inflammations such as a chemical inflammation owing to POPF, a bacterial inflammation, or both. Therefore, administration of antibacterial drugs should be considered, although the cause of FC infection after distal pancreatectomy is unknown [18, 19].
The choice between a specific intervention or conservative treatment for PIAA is uncertain and mainly depends on each surgeon’s discretion. Thus, the first-line treatment for PIAA remains unclear. Here, the postoperative stay of PIAA patients with interventional drainage was longer than that of those without these treatments (28 days vs 17.5 days, P < 0.001) because most PIAA patients with interventional drainage had conservative treatments initially. Our data also showed that more patients in the drainage group had diabetes mellitus, high HbA1c levels, and open surgery. Diabetes mellitus is a known risk factor for postoperative complications after various surgeries [20, 21], and a meta-analysis [22] has revealed that laparoscopic surgery in patients with obesity reduces surgical site infection in open surgery across general abdominal surgical procedures; thus, we may consider interventional treatments for PIAA initially for these patients. Among PIAA patients with interventional drainage, amylase levels in all punctured abscesses were thrice the upper limit of institutional normal serum values. This high amylase level in the punctured abscess may have occurred secondarily owing to the inflammatory extension of the pancreatic stump from PIAA. Although interventional treatments may occasionally result in secondary events, the use of various interventions has been recently increasing and becoming gradually safe, especially in special hospitals [23, 24]. In the future, studies should further investigate predictive factors for PIAA in patients with CR-POPF.
This study had several limitations. First, this was a retrospective study of consecutive patients from two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons, so selection bias was minimized. Second, the choice between conducting an open approach or a laparoscopic approach for distal pancreatectomy depended on each surgeon and varied through time. Recently, laparoscopic distal pancreatectomy for pancreatic cancer has been included in insurance coverage; thus, the number of laparoscopic distal pancreatectomies for pancreatic cancer has been increasing. Finally, the timing of intervention for PIAA was also based on the subjective judgment of each surgeon. Therefore, future prospective research studies are needed to confirm and evaluate these preliminary findings.
In conclusion, in the univariate analysis, preoperative indices representing abdominal fat mass (i.e., BMI, SFA, and VFA) were identified as predictive factors for PIAA, and the CRP level on POD 3 was an independent and significant predictive factor for PIAA and CR-POPF after distal pancreatectomy. PIAA may not occur postoperatively if there are less visceral adipose tissues around the surgical site, which may be dissolved by pancreatic juice, even if subclinical and potential leakage of pancreatic juice may continue to occur postoperatively.