Evaluation of preoperative risk factors for postpancreatectomy hemorrhage

Recently, the surgical technique for pancreatectomy has improved; however, pancreatectomy is associated with many complications postsurgery [1‐4]. Although the frequency of postpancreatectomy hemorrhage (PPH) is not high, it results in severe adverse outcomes. The incidence rate of PPH and the mortality rate following PPH have been reported to be 3–16% and 16–36%, respectively [4‐12]. The International Study Group on Pancreatic Surgery (ISGPS) defined PPH in 2007 [13]. Some studies have reported that postoperative pancreatic fistula (POPF), postoperative bile leakage, and postoperative abdominal infection are risk factors for PPH [5‐12]. Although this information is useful, it includes intraoperative and postoperative factors that can only be known after surgery. Other studies reported that male sex, high body mass index (BMI), and low serum albumin (Alb) levels, which are preoperative factors, are associated with PPH [8, 10, 12, 14]. However, the preoperative risk factors for PPH have not been fully elucidated yet. Therefore, the aim of this study was to clarify the preoperative risk factors for PPH.

Between 2005 and 2018, 1169 patients underwent pancreatectomy at the Department of Surgery, Institute of Gastroenterology, Tokyo Woman’s Medical University. Parameters that were evaluated included the incidence, outcomes, time of onset, location, severity, grade, and risk factors of PPH. Clinical data that were collected and examined included age; sex; preoperative BMI; white blood cell (WBC) count; serum levels of Alb, C-reactive protein (CRP), and hemoglobin A1c (HbA1c); preoperative drainage for obstructive jaundice; preoperative treatment (chemotherapy or chemoradiotherapy); operative procedure, duration of surgery; amount of intraoperative blood loss; vascular resection; pancreatojejunostomy (PJ) anastomosis method; falciform ligament wrapping of the gastroduodenal artery (GDA) stump; clipping of the GDA stump; PJ stent; pathological tissue type; pancreatic fistula; delayed gastric emptying (DGE); and postoperative bile leakage. The significant factors identified by multivariate analysis to cause PPH were defined as risk factors for PPH. The risk score was calculated, with 1 point assigned to each risk factor, and the incidence of PPH was examined for each risk score number.

The patients’ characteristics for all pancreatectomies are shown in Supplemental Table 1. Six hundred fifty-five patients (56%) were men; the median preoperative BMI level was 21.5 kg/m² (range 14.3–36.8 kg/m²); 421 patients (36%) had diabetes mellitus (DM); 675 patients (57%) underwent pancreatoduodenectomy (PD); 211 patients (18%) had POPF grade B (15.6%, 182 patients) or C (2.5%, 29 patients); 279 (24%) patients underwent HDL wrapping of the GDA stump; none of the patients with omental grafts underwent GDA stump wrapping, and all patients underwent vascularized graft placement of the GDA stump using the falciform ligament; 26 (2%) patients underwent clipping of the GDA stump.

This study indicates that absence of DM (HbA1c level ≤ 6.2%) is an independent risk factor for PPH after all pancreatectomies and PD and for POPF after PD; a risk scoring system including the absence of DM may be useful for predicting PPH before surgery. By determining the value of HbA1c level (≤ 6.2%), we can predict PPH more easily. This is a new finding that has not been reported before.

In recent years, PPH has a low frequency, but it has a poor outcome. POPF, DGE, wound infection, and abdominal abscess are major complications of PD [3, 4, 17]. Previous literatures reported that the incidence of PPH was only 3–16%; however, mortality among patients with PPH was 16–36% [4‐12]. In this study, the incidence and mortality rates of patients with PPH were 3% (35/1169) and 11% (4/35), respectively (Table 1), after all pancreatectomies. PPH was the major cause of death within 30 days after pancreatectomy. Previous literatures also reported that short-term outcomes after pancreatectomy were better in high-volume centers than in low-volume centers (mortality rate 0.9–6.0% vs. 13.0–18.8%) [9, 18‐20].

Some previous reports about intraoperative and postoperative factors showed that vascular resection, pancreaticogastrostomy, postoperative bile leakage, postoperative abdominal infection, and especially POPF were independent risk factors for PPH [5‐12]. PPH from a pseudoaneurysm of the GDA stump usually results from POPF [9, 21], and the median onset time of PPH was reported as 5–13 days (range 0–58 days) [6, 10, 12]. In our study, similar results were noted, and it is necessary to pay attention to the onset time from initial surgery (median onset time 22 days, range 0–65 days; Table 1). Previous literatures have mentioned preoperative risk factors for PPH such as male sex, high BMI, and low Alb level [8, 10, 12, 14]; our study also showed a similar result. Additionally, in our study, “absence of DM (HbA1c level ≤ 6.2%)” was one of the significant independent risk factors for PPH after all pancreatectomies and PD, which has not been reported.

Insulin acts to promote secretion of pancreatic exocrine cells [22]. It has been reported that the pancreatic exocrine function declined as insulin secretion decreased and the exocrine pancreatic glands atrophied [23]. This means that in patients with DM, the pancreatic parenchyma atrophies and becomes hard, and in patients without DM, the pancreatic parenchyma is thick and soft. Traditionally, patients with a soft pancreas, thick parenchyma, and thin pancreatic duct are considered at risk for POPF after PD [24‐27]. Pancreatic exocrine function is an important determinant of POPF after PD [28]. In pancreatic carcinoma, it has been reported that pancreatic parenchyma atrophy is seen from the onset of illness and the main pancreatic duct is dilated [29]. In the same way, in a patient with intraductal papillary mucinous neoplasm, the main pancreatic duct is slightly dilated and the pancreatic parenchyma is relatively decreased and atrophic. In contrast, in patients with distal extrahepatic bile duct carcinoma, main pancreatic duct dilation and pancreatic parenchyma atrophy are rare. Patients with a thick and soft pancreatic parenchyma have a high possibility of POPF and a high risk of PPH after pancreatectomy. In situations where there is no clear definition of the thickness and hardness of the pancreas and it is difficult to judge them preoperatively, the presence or absence of DM (HbA1c level ≤ 6.2%) is considered to be one of the good indicators.

Previous literatures reported that omental flaps or grafts around various anastomoses after PD could reduce the incidence of POPF and PPH [30, 31]. In this study, the statistical analysis did not show a significant benefit of wrapping the GDA stump for preventing PPH. We believe we cannot draw sufficient statistical conclusions because of differences in surgical techniques and instruments, differences in applications and methods of round ligament wrapping, and the limited use of clips in recent cases. Hence, further clinical evaluation for this is necessary. In addition, pancreatic surgery in patients at high risk for developing PPH may require new precautions to further reduce the incidence of PPH.

Male sex, BMI ≥ 25 kg/m², absence of DM (HbA1c level ≤ 6.2%), and PD are independent risk factors for PPH after all pancreatectomies. A risk scoring system including the new preoperative risk factor “absence of DM” would be useful for predicting PPH.