Chronic pancreatitis of the pancreatic remnant is an independent risk factor for pancreatic fistula after distal pancreatectomy

A pancreatic resection left of the superior mesenteric artery (SMA) is termed left resection or distal pancreatectomy (DP). This pancreatic resection technique can be performed, according to the indication of the operation, as a spleen-preserving resection, or it can be combined with a splenectomy. There are various indications for a distal pancreatectomy. The most common indications are patients with malignant diseases, cystic or neuroendocrine tumors or even chronic pancreatitis [1]. A major cause of postoperative morbidity is the development of a pancreatic fistula (POPF). A pancreatic fistula after DP can lead to hemorrhages, abscesses, sepsis or wound infections [2]. A variety of procedures have been recommended to reduce the frequency of pancreatic fistula [2, 3]. In particular, the stapler transection and the hand-sewn closure technique have been widely analyzed. For both techniques, a fistula rate of approximately 30% has been reported [4, 5]. The present analysis demonstrates our experience with the hand-sewn closure technique (including separately stitched ligation of the pancreatic duct) at a single German pancreatic center. The primary outcome of our study was the formation of a pancreatic fistula. Furthermore, we analyzed our data regarding the risk factors for the development of a POPF.

The technique of stump closure after DP has been widely debated. Different approaches have been tested in various studies, and in a comparative analysis, no significant advantage for any specific method was detected [8]. Recent publications, such as the DISPACT trial, have compared the stapler and the hand-sewn closure techniques. No difference between these techniques was shown in regard to POPF [4]. Moreover a current randomized controlled trial by Carter et al. evaluated the additional effect of fibrin glue or autologous falciform patch after stapler or hand- sewn closure of the pancreatic remnant [5]. They found no benefit for this additional measure regarding POPF. Finally, various studies evaluated the use of somatostatin analogues perioperatively or postoperatively. However, a meta-analysis by Koti et al. found a decrease of morbidity only in selected patients [9]. Thus, POPF remains a major source of morbidity and is therefore a relevant clinical problem after DP even though it does not lead to a high postoperative mortality. Considering this background, we present our experiences with the hand-sewn closure technique in the current report.

In our study, we specifically focused on factors contributing to pancreatic fistula. In the present series, all DPs were performed during open laparotomy using the same technique of selective ligation of the pancreatic duct. Currently, there is a tendency to perform this operation laparoscopically. This approach, however, presents the same complications as those associated with open resection and stapler closure; safe closure of the pancreatic remnant is therefore an important issue for laparoscopic distal pancreatectomy [10].

During the follow up, nearly half of the patients (45%) showed a POPF after PD. However, a clinically relevant POPF (grade B/C) was evaluated in only 21% of the cases. These results are consistent with the published data [5, 11, 12,]. The recently published DISPACT trial showed comparable results related to POPF (approximately 20-21%) for the stapler transection and the hand-sewn closure technique [4]. By using a standardized closure technique, we could reproduce the published results for development of a clinically relevant POPF in our cohort. Although it should be noted that the present study is a retrospective analysis.

We support the importance of the selective ligation of the pancreatic duct. A previous study by Pannegeon et al. [11] confirmed the findings of a multivariate analysis by Bilimoria et al. [12] indicating that specific ligation of the main pancreatic duct is an independent protective factor for POPF. Other authors have noted that an inability to find the main pancreatic duct for ligation is a major factor related to the occurrence of postoperative fistula [13].

In our study, chronic pancreatitis of the pancreatic remnant was identified as an independent risk factor for POPF in the univariate (p = 0.007) and multivariate analyses (OR 7.09) (Table 2 and 3). Similarly to other authors, we believe that this is due to downstream stenosis of the main pancreatic duct, most likely in the pancreatic head region, due to chronic inflammation. Preoperative diabetes was not detected as a significant risk factor for POPF in our analysis, but it is important to note that in most cases, diabetes is concomitant with chronic pancreatitis and therefore could be a preoperative indicator [14]. We infer from our data that in cases with a potential obstruction of the pancreatic duct in the pancreatic head/periampullary region (e.g. due to chronic pancreatitis), and therefore an increased likelihood of POPF, the pancreatic remnant should be anastomosed. This seems especially important in patients with preoperatively or intraoperatively detected dilatation of the pancreatic duct. Pancreatic anastomosis seems to be a safe method of closure in these cases after DP. However, one could speculate that pancreatic leakage following small bowel anastomosis could result in potentially more serious complications than leakage without anastomosis (e.g. activation of pancreatic enzymes, bacterial contamination). Therefore, a pancreatic anastomosis following DP should only be performed if it can be carried out safely [15].

Hypertension has also been noted as a risk factor for the development of POPF in our analyses. This might be due to the pathophysiological effect of hypertension, which causes generalized atherosclerosis and thereby limits the microcirculation of the tissue. Perfusion is a particularly important factor for wound healing. By compromising the healing process, hypertension could negatively affect the postoperative course. This negative effect of hypertension has been reported previously [16]. Moreover, hypertension is also a parameter of the POSSUM score, which accurately predicts morbidity in various operation procedures [17, 18].

In addition, our analysis confirms that patients with a clinically relevant pancreatic fistula had a mean extension of their hospital stay (B/C fistula (26.3 days) vs. no fistula/grade A fistula (13.7 days)) (p < 0.001). This tendency was also recently reported by the DISPACT trial [4].

Our data support the assumption that DP can now be performed without significant mortality (i.e., 1.6% in our analysis) [4, 11, 18]. However, the morbidity after DP is still high due to the occurrence of POPF. By selective stitched ligation of the pancreatic duct and fish-mouth closure of the pancreatic remnant, a low POPF rate comparable to the results in the literature could be achieved. Chronic inflammation of the pancreatic remnant should be considered a risk factor for POPF during the intraoperative decision process for stump closure, and maybe an anastomosis of the remnant to the small intestine, e.g. using a jejunal limb, should be considered in these cases.