risk factors for post-pancreaticoduodenectomy bleeding and finding an innovative approach to...

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Original Paper

Dig Surg 2009;26:297–305 DOI: 10.1159/000228245

Risk Factors for Post-Pancreaticoduodenectomy Bleeding and Finding an Innovative Approach to Treatment

Hung-Kuang Wei a Shin-E Wang a Yi-Ming Shyr a Hsiuo-Shan Tseng b

Wan-Chen Tsai b Tien-Hua Chen a Cheng-Hsi Su a Chew-Wun Wu a

Wing-Yiu Lui a

Departments of a Surgery, Taipei Veterans General Hospital, and b Radiology, Koo Foundation Sun Yat-SenCancer Center and Taipei Veterans General Hospital, National Yang Ming University, Taipei , Taiwan

failure. Conclusions: The placement of metallic clips on the gastroduodenal artery stump during a pancreaticoduode-nectomy is helpful in identifying overlooked intermittent sentinel bleeding during angiography. Transarterial emboli-zation for gastroduodenal artery bleeding could not guaran-tee against hepatic failure. The intravascular placement of a covered stent is the preferred procedure to avoid the com-plete interruption of arterial blood supply to the liver.

Copyright © 2009 S. Karger AG, Basel

Introduction

Surgical mortality after pancreaticoduodenectomy has decreased to under 5% in most high-volume centers, but morbidity remains high, ranging from 18 to 52% [1–4] . The most frequent causes of morbidity are delayed gastric emptying and pancreatic leakage [1–2] . The inci-dence of pancreatic leakage has been reported to be 3.7–25%, with an average of 13.6% [4] . Pancreatic leakage of-ten carries a mortality rate of 8–40% because this may result in further serious complications, e.g. intra-abdom-inal abscess, sepsis and bleeding [3–8] . Post-pancreatico-duodenectomy bleeding is the major concern once pan-creatic leakage occurs [3, 9] . According to the literature, the outcome of post-pancreaticoduodenectomy bleeding

Key Words

Post-pancreaticoduodenectomy bleeding � Gastroduodenal artery � Transarterial embolization � Covered stent

Abstract

Background: This study is to determine the risk factors and outcome for post-pancreaticoduodenectomy bleeding, and to assess the roles of surgery and intravascular intervention in its management. Methods: Post-pancreaticoduodenecto-my data of 628 patients were analyzed with regards to post-pancreaticoduodenectomy bleeding. Results: Post-pancre-aticoduodenectomy bleeding occurred in 58 patients (9.2%) and led to death in 23 patients. Pancreatic leakage and intra-abdominal abscess were independent risk factors for both extraluminal and intraluminal post-pancreaticoduodenec-tomy bleeding. The most common source of bleeding was the gastroduodenal artery (n = 9, 24.3%), and 8 of these pa-tients (88.9%) experienced gastroduodenal artery bleeding in late post-pancreaticoduodenectomy bleeding. Hemo-stasis for post-pancreaticoduodenectomy bleeding was achieved by surgery in 22 patients (78.6%) and intravascular intervention in 7 patients (58.3%). Transarterial embolization for gastroduodenal artery bleeding did not deteriorate liver function in most patients except for 1 who died of hepatic

Received: October 17, 2008 Accepted: March 28, 2009 Published online: July 11, 2009

Yi-Ming Shyr, MD Division of General Surgery, Department of SurgeryVeterans General Hospital, 201 Section 2 Shih-Pai Road Taipei 112 (Taiwan) Tel. +886 2 2875 7652, Fax +886 2 2875 7537, E-Mail [email protected]

© 2009 S. Karger AG, Basel0253–4886/09/0264–0297$26.00/0

Accessible online at:www.karger.com/dsu

http://dx.doi.org/10.1159%2F000228245

Wei /Wang /Shyr /Tseng /Tsai /Chen /Su /Wu /Lui

Dig Surg 2009;26:297–305298

is often unfavorable, with a mortality rate of about 60% [3, 5, 9, 10] . Deciding on the optimal management of life-threatening post-pancreaticoduodenectomy bleeding is difficult, especially for late bleeding. Management of post-pancreaticoduodenectomy bleeding is often dictat-ed by the clinical status of each individual patient, avail-able medical equipment and institutional preferences. The endoscopic approach is feasible mainly for gastroin-testinal (intraluminal) bleeding; reoperation is tradition-ally reserved for intra-abdominal (extraluminal) bleed-ing, but carries substantial morbidity and mortality for late bleeding [3, 10] . Intravascular intervention, such as transarterial embolization or the placement of covered stents to occlude the orifice of the bleeding vessel, is a minimally invasive procedure and can be considered as a good alternative to reoperation [2–3, 5, 9–20] . Therefore, determining the risk factors for post-pancreaticoduode-nectomy bleeding and accumulating treatment experi-ence is of utmost importance for pancreatic surgeons.

The aims of this study are to determine the risk factors and outcome for post-pancreaticoduodenectomy bleed-ing. We also assess the roles of surgery and intravascular intervention by transarterial embolization or the place-ment of a covered stent in the management of post-pan-creaticoduodenectomy bleeding.

Materials and Methods

Clinical data were retrieved for analysis from our prospec-tively collected computer database of 628 patients with resectable periampullary lesions who underwent a pancreaticoduodenecto-my between January 1980 and December 2007. Detailed data re-garding the time and source of post-pancreaticoduodenectomy bleeding were also retrospectively assessed by a thorough review of medical records when possible. Based on the definitions and classifications of postpancreatectomy hemorrhage proposed by the International Study Group of Pancreatic Surgery (ISGPS) [21] , the cases were classified into ISGPS grades A, B and C, and cate-gorized into intraluminal or extraluminal, mild or severe, and early or late groups. Intraluminal post-pancreaticoduodenecto-my bleeding referred to bleeding inside the gastrointestinal tract, and extraluminal post-pancreaticoduodenectomy bleeding was in tra-abdominal bleeding outside the gastrointestinal tract. Ear-ly post-pancreaticoduodenectomy bleeding was defined as bleed-ing within 24 h after the pancreaticoduodenectomy, and latepost-pancreaticoduodenectomy bleeding was defined as bleeding more than 24 h after the pancreaticoduodenectomy.

The incidence, treatment modality and outcome of post-pan-creaticoduodenectomy bleeding were evaluated. A variety of risk factors for post-pancreaticoduodenectomy bleeding were deter-mined for univariate and multivariate analysis, including the type of pancreatic anastomosis, consistency of pancreas paren-chyma, pancreatic duct stenting, the diameter of pancreatic duct,

surgeon volume, patients’ age, pancreatic leakage, bile leakage, gastrojejunostomy leakage, intra-abdominal abscess formation, a primary periampullary lesion and serum levels of total bilirubin. To provide direct evidence of pancreatic anastomosis leakage, up-per gastrointestinal studies (oral intake of 2 ml of methylene blue dye plus 200 ml of water) or a fistulogram were performed in cases in which pancreatic leakage were suspected. Pancreatic leakage was defined as a leak of methylene blue dye into a drain or positive fistulogram findings during the postoperative period [4, 22] . Pancreas texture was determined by gross examination and significant fibrotic change by microscopic examination.

Surgical Technique Pancreaticoduodenectomiy was performed with either a pylo-

rus-preserving modification or a classic resection including an-trectomy. Pancreatic reconstruction could be done by a pancreati-cogastrostomy or pancreaticojejunostomy. The surgical technique (pancreaticogastrostomy or pancreaticojejunostomy) was selected according to the surgeon’s preference. In the pancreaticogastros-tomy group, the pancreatic stump was anastomosed and invagi-nated into the midbody posterior wall of the stomach with inter-rupted 2-layer sutures: 3-0 silk for the outer layer placed between the pancreatic capsule and seromuscular layer of the posterior gas-tric wall, and 3-0 polyglactin (Vicryl; Ethicon Inc., Somerville, N.J., USA) for the inner layer placed between the cut edge of the pan-creas and the full thickness of the posterior gastric wall. Pancre-atic duct stents were not used in the pancreaticogastrostomies. In the pancreaticojejunostomy group, pancreatico jejunostomies were performed by end-to-side, 2-layer sutures, using the same suture materials as for the pancreaticogastrostomies. The 1st layer suture was a duct-to-mucosa anastomosis with 6–8 sutures, and the 2nd layer suture was between the cutting edge of the pancreas and the seromuscular edge of the jejunum. A pancreatic duct stent was usu-ally used in the pancreaticojejunostomies. Two latex closed-suction tubes were used to drain the areas near the pancreatic anastomosis. For accurate and prompt localization of gastroduodenal artery bleeding, the gastroduodenal artery stump was routinely marked by 2 metallic clips after dividing it, starting in the year 2000.

Statistical Analysis Statistical analysis was carried out using the SPSS 16.0 soft-

ware program (Statistic Package for Social Sciences; SPSS Inc., Chicago, Ill., USA). All continuous data were presented as median and range. Categorical variables were compared by a � 2 test or Fisher’s exact test. A Mann-Whitney U test or Wilcoxon test was used to compare the continuous variables. Logistic regression multivariate analysis was carried out to determine the indepen-dent risk factors for post-pancreaticoduodenectomy bleeding. A p value ! 0.05 was considered statistically significant.

Results

Post-pancreaticoduodenectomy bleeding occurred in 58 of 628 patients (9.2%) who underwent a pancreatico-duodenectomy, including 21 intraluminal (36.2%) and 37 extraluminal (63.8%) types. There were 45 males and 13 females with a median age of 67 years (range 36–84).

Post-Pancreaticoduodenectomy Bleeding Dig Surg 2009;26:297–305 299

Overall, pancreaticoduodenectomy resulted in surgi-cal mortality in 7.0% of the patients (44/628), with 3.2% (10/309) in the pancreaticogastrostomy group and 10.7% (34/319) in the pancreaticojejunostomy group (p = 0.000). The mortality rate was 39.7% (23/58) for all patientswith post-pancreaticoduodenectomy bleeding, including 28.6% for the intraluminal type (6/21) and 45.9% for the extraluminal type (17/37; p = 0.194). Therefore, 52.3% (23/44) of the patients died as a result of post-pancre-aticoduodenectomy bleeding. Using univariate analy-sis, pancreatic leakage, bile leakage, gastrojejunostomy leakage and intra-abdominal abscess were risk factorsfor overall post-pancreaticoduodenectomy bleeding ( ta-ble 1 ). Post-pancreaticoduodenectomy bleeding occurred in 15 of the 61 patients (24.6%) with pancreatic leakage, 5 of the 19 patients (26.3%) with bile leakage, 3 of the 6 pa-tients (50.0%) with gastrojejunostomy leakage and 25 of the 69 patients (36.2%) with an intra-abdominal abscess. Although the overall incidence of pancreatic head cancer was highest among the periampullary cancers, the num-ber (246) of resected ampullary cancers was higher than that of resected pancreatic head cancers with lower re-sectability (174). Among the 58 patients with post-pan-creaticoduodenectomy bleeding, 25.9% were associated with pancreatic leakage, 8.6% with bile leakage, 5.2% with gastrojejunostomy leakage and 43.1% with intra-ab-dominal abscess. For extraluminal post-pancreaticoduo-denectomy bleeding, the type of pancreatic anastomosis, pancreatic leakage, gastrojejunostomy leakage and intra-abdominal abscess were risk factors. Pancreatic leakage and intra-abdominal abscess were risk factors for in-traluminal post-pancreaticoduodenectomy bleeding ( ta-ble 2 ).

After multivariate analysis ( table 3 ), pancreatic leak-age, gastrojejunostomy leakage and intra-abdominal abscess were still independent risk factors for overall post-pancreaticoduodenectomy bleeding and extralumi-nal post-pancreaticoduodenectomy bleeding. Pancreatic leakage and intra-abdominal abscess were independent risk factors for intraluminal post-pancreaticoduodenec-tomy bleeding.

Among the 58 patients with post-pancreaticoduode-nectomy bleeding, determining the accurate time and lo-cation of the bleeding could be retrospectively assessed on 37 patients by a thorough review of their medical records, consisting of 6 early and 31 late post-pancreati-coduodenectomy bleeding cases ( table 4 ). According to ISGPS definition, our 37 cases of post-pancreaticoduo denectomy bleeding were classified into 1 grade A, 16grade B and 20 grade C cases. Ten belonged to mild post-

Table 1. Univariate analysis of risk factors for overall PPDB

Risk factor Overall PPDB pvalueno yes

Type of anastomosis 0.082PG (n = 309) 286 (92.6) 23 (7.4)PJ (n = 319) 284 (89.0) 35 (11.0)Pancreas texture 0.128Soft (n = 262) 239 (91.2) 23 (8.8)Hard (n = 168) 159 (94.6) 9 (5.4)Pancreatic duct stenting 0.342With (n = 183) 171 (93.4) 12 (6.6)Without (n = 247) 227 (91.9) 20 (8.1)Pancreatic duct 0.461Dilated (>5 mm) (n = 112) 103 (92.0) 9 (8.0)Nondilated (≤5 mm) (n = 318) 295 (92.8) 23 (7.2)Surgeon volume 0.370Low (<10) (n = 64) 55 (85.9) 9 (14.1)Medium (10–20) (n = 36) 33 (91.7) 3 (8.3)High (>20) (n = 528) 482 (91.3) 46 (8.7)Age 0.490≤65 years (n = 288) 262 (91.0) 26 (9.0)>65 years (n = 340) 308 (90.6) 32 (9.4)Pancreatic leakage 0.000Yes (n = 61) 46 (75.4) 15 (24.6)No (n = 567) 524 (92.4) 43 (7.6)Bile leakage 0.024Yes (n = 19) 14 (73.7) 5 (26.3)No (n = 609) 556 (91.3) 53 (8.7)Gastrojejunostomy leakage 0.012Yes (n = 6) 3 (50.0) 3 (50.0)No (n = 622) 567 (91.2) 55 (8.8)Intra-abdominal abscess 0.000Yes (n = 69) 44 (63.8) 25 (36.2)No (n = 559) 526 (94.1) 33 (5.9)Primary lesions 0.128Ampullary cancer (n = 246) 217 (88.2) 29 (11.8)Duodenal cancer (n = 37) 33 (89.2) 4 (10.8)Distal CBD cancer (n = 54) 46 (85.2) 8 (14.8)Pancreatic head cancer (n = 174) 165 (94.8) 9 (5.2)IPMN (n = 27) 23 (85.2) 4 (14.8)Chronic pancreatitis (n = 38) 37 (97.4) 1 (2.6)Others (n = 52) 49 (94.2) 3 (5.8)Total serum bilirubin level 0.331≥15 mg/dl (n = 320) 289 (90.3) 31 (9.7)<15 mg/dl (n = 102) 90 (88.2) 12 (11.8)

Figures in parentheses are percentages. PPDB = Post-pancre-aticoduodenectomy bleeding; PG = pancreaticogastrostomy; PJ = pancreaticojejunostomy; CBD = common bile duct; IPMN = in-traductal papillary mucinous neoplasm.


Dig Surg 2009;26:297–305300

pancreaticoduodenectomy bleeding and 27 belonged to severe post-pancreaticoduodenectomy bleeding. There were no deaths from early post-pancreaticoduodenec-tomy bleeding, but 10 deaths (32.3%) from late post-pancreaticoduodenectomy bleeding (p = 0.127). In early

post-pancreaticoduodenectomy bleeding cases, there were 2 intraluminal (33.3%) and 4 extraluminal bleeding (66.7%) cases. In late post-pancreaticoduodenectomy bleeding cases, there were 12 intraluminal (38.7%) and 19 extraluminal bleeding (61.3%). The most common source of post-pancreaticoduodenectomy bleeding was the gas-troduodenal artery occurring in 24.3% of the cases (9/37), of which 88.9% (8/9) were late post-pancreaticoduode-nectomy bleeding (p = 0.039). While the gastroduodenal artery (25.8%) was the most common site of late post-pancreaticoduodenectomy bleeding, the stomach edgeof the pancreaticogastrostomy (33.3%) was the most common site in early post-pancreaticoduodenectomy bleeding. 28 patients (75.7%) underwent reoperation for post-pancreaticoduodenectomy bleeding, and 12 patients (32.4%) received intravascular intervention. All 6 patients (100%) with early post-pancreaticoduodenectomy bleed-ing eventually underwent an operation for bleeding, while only 22 patients (71.0%) with late post-pancreatico-duodenectomy bleeding were treated so (p = 0.162). Sur-gery achieved hemostasis in 22 patients (78.6%; 6 early bleeding, 16 late bleeding) and failed in 4 (14.3%). No bleeder could be found during operation in 2 patients (7.1%). Intravascular intervention was attempted in 1 pa-tient (16.7%) with early post-pancreaticoduodenectomy bleeding and 11 patients (35.5%) with late post-pancre-

Table 2. Univariate analysis of risk factors for extraluminal and intraluminal PPDB

Risk factor Extraluminal PPDB p value Intraluminal PPDB p value

no yes no yes

Type of anastomosis 0.040 0.055PG (n = 309) 296 (95.8) 13 (4.2) 299 (96.8) 10 (3.2)PJ (n = 319) 294 (92.2) 25 (7.8) 299 (93.7) 20 (6.3)

Pancreatic leakage 0.000 0.000Yes (n = 61) 49 (80.3) 12 (19.7) 51 (83.6) 10 (16.4)No (n = 567) 541 (95.4) 26 (4.6) 547 (96.5) 20 (3.5)

Bile leakage 0.101 0.229Yes (n = 19) 16 (84.2) 3 (15.8) 17 (89.5) 2 (10.5)No (n = 609) 574 (94.3) 35 (5.7) 581 (95.4) 28 (4.6)

Gastrojejunostomy leakage 0.046 0.255Yes (n = 6) 4 (66.7) 2 (33.3) 5 (83.3) 1 (16.7)No (n = 622) 586 (94.2) 36 (5.8) 593 (95.3) 29 (4.7)

Intra-abdominal abscess 0.000 0.000Yes (n = 69) 49 (71.0) 20 (29.0) 57 (82.6) 12 (17.4)No (n = 559) 541 (96.8) 18 (3.2) 541 (96.8) 18 (3.2)

Figures in parentheses are percentages. PPDB = Post-pancreaticoduodenectomy bleeding; PG = pancreati-cogastrostomy; PJ = pancreaticojejunostomy.

Table 3. Independent risk factors for PPDB by multivariate anal-ysis

Risk factors p value OR CI

Overall PPDBPancreatic leakage 0.000 3.579 1.789–6.123Bile leakage 0.235 2.051 0.627–6.706Gastrojejunostomy leakage 0.017 9.183 1.493–56.494Intra-abdominal abscess 0.000 7.828 4.231–14.481

Extraluminal PPDBOperation type 0.888 1.058 0.484–2.312Pancreatic leakage 0.002 3.850 1.636–9.061Gastrojejunostomy leakage 0.026 9.344 1.315–66.408Intra-abdominal abscess 0.000 11.073 5.317–23.057

Intraluminal PPDBPancreatic leakage 0.000 4.947 2.253–10.860Intra-abdominal abscess 0.000 4.539 2.071–9.951

PPDB = Post-pancreaticoduodenectomy bleeding; OR = odds ratio; CI = 95% confidence interval.


aticoduodenectomy bleeding (p = 0.350). Intravascular intervention stopped the bleeding in 7 patients (58.3%; all were late post-pancreaticoduodenectomy bleeding), but failed in 2 patients (16.7%). No bleeder could be identified during angiography in 3 patients (25%). One patient pre-sented with sentinel bleeding and blood around the gas-troduodenal artery stump on computed tomography, but no pseudoaneurysm or active bleeding was detected on the 1st attempt in angiography. Rebleeding occurred 1 week later and angiography still failed to detect the active bleeder. Nevertheless, transarterial embolization was performed under the presumption of gastroduodenal ar-tery stump bleeding. The gastroduodenal artery stump was easily and accurately localized by angiography be-cause it had already been marked with metallic clips dur-ing the pancreaticoduodenectomy ( fig. 1 ). Transarterial embolization under the guide of clips marking the gas-troduodenal artery stump worked very well, and no bleeding occurred thereafter. Among the 7 patients with successful intravascular intervention, the placement of a covered stent (Bard; Angiomed GmbH & Co., Karlsruhe, Germany) was performed in 1 patient ( fig. 2 ) and trans-arterial embolization with coils (Cook Inc., Blooming-ton, Ind., USA) in 6 patients. To stop the gastroduodenal artery bleeding, the common hepatic artery (CHA) would inevitably be occluded during transarterial embolization. Table 5 shows the effect of liver functions by transarte-rial embolization with the coil occlusion of the CHA. There were no significant changes on days 1 and 7 after transarterial embolization, as compared with those be-fore the procedure. One patient died of hepatic failure due to complete occlusion of the CHA in spite of success-ful cessation of the gastroduodenal artery bleeding by transarterial embolization.

Discussion

Post-pancreaticoduodenectomy bleeding, with an in-cidence of 9.2% in this study and 2–20% in the literature [3, 9] , is a potentially lethal complication with a 39.7% mortality rate in our series and 8–60% in the literature [3, 5, 9, 10] . More than half (52.3%) of the patient deaths were a result of post-pancreaticoduodenectomy bleeding in our study. Anastomotic leakage and infectious events play a major role in developing post-pancreaticoduode-nectomy bleeding [3, 11] . Our study also confirms that pancreatic leakage and intra-abdominal abscess are inde-pendent risk factors for both extraluminal and intralu-minal post- pancreaticoduodenectomy bleeding. Gastro-

Table 4. Characteristics of early and late PPDB

Early PPDB(n = 6)

Late PPDB(n = 31)

Type of bleedingIntraluminal 2 (33.3) 12 (38.7)Extraluminal 4 (66.7) 19 (61.3)

Source of bleedingGDA 1 8*Stomach edge of PG 2 4Pancreas edge of PG 0 1Jejunal edge of PJ 0 2Artery in mesentery 1 0SMV tributary 0 1Omental vessel 0 1Gastroenterostomy 0 1Marginal ulcer 0 2Unknown origin 0 6Others 2 5

Management of PPDBEndoscopy 0 8 (25.8)TAE 1 (16.7) 11 (35.5)Operation 6 (100) 22 (71.0)

OutcomeAlive 6 (100) 21 (67.7)Dead 0 10 (32.3)

Figures in parentheses are percentages. * p = 0.039 for early vs. late PPDB. PPDB = Post-pancreaticoduodenectomy bleeding; GDA = gastroduodenal artery; PG = pancreaticogastrostomy;PJ = pancreaticojejunostomy; SMV = superior mesenteric vein; TAE = transarterial embolization.

Table 5. Liver function results after TAE with coils for PPDB from GDA (n = 6)

ASTunits/l

ALTunits/l

T. bil.mg/dl

Before TAEMedian 30.0 31.0 0.9Range 17–100 11–80 0.4–3.7

Day 1 after TAEMedian 49.5 31.5 1.5Range 11–4,339 12–1,647 0.5–2.3

Day 7 after TAEMedian 25.0 15.5 0.6Range 17–1517 12–913 0.6–6.8

p value day 0 vs. 1 0.173 0.600 0.345p value day 0 vs. 7 0.917 0.686 0.345p value day 1 vs. 7 0.207 0.173 0.600

TAE = Transarterial embolization; PPDB = post-pancreatico-duodenectomy bleeding; GDA = gastroduodenal artery; AST = aspartate aminotransferase; ALT = alanine aminotransferase;T. bil. = total bilirubin.


Dig Surg 2009;26:297–305302

Patient CHA with a covered stent

GDA bleeding

X2 Distance: 5.90 mm X2

X1 Distance: 6.96 mmX1

GDA stump marked with clipsTAE with coils for CHA andGDA stump marked with clips

Fig. 1. No active bleeder or pseudoaneurysm could be identified during the 1st angiographic attempt for an episode of sentinel bleeding. Note that the gastroduodenal artery (GDA) stump was marked by clips (left pic-ture). Transarterial embolization (TAE) was still successfully performed for the intermittent bleeding of the GDA stump clearly marked by clips (right picture).

Fig. 2. A pseuodoaneurysm with bleeding from the GDA stump marked with clips was noted on angiography (left picture). Angiography of a patient’s CHA with a covered stent (right picture).


jejunostomy leakage is another independent risk factor for extraluminal post-pancreaticoduodenectomy bleed-ing.

Patients with post-pancreaticoduodenectomy bleed-ing are divided into early and late groups because the pathogenesis and optimal management might differ. Management of the early group is usually more straight-forward with a better outcome compared to the late group [1, 3, 9] . In our series, bleeding from the stomach edge of the pancreaticogastrostomy (33.3%) was the most com-mon site in the early group. Additionally, all early group patients and 71.0% of the late group patients eventually underwent reoperation. The outcome seemed favorable in the early group as no deaths occurred, but mortality was 32.3% in the late group. Early post-pancreaticoduo-denectomy bleeding was more likely to be related to some surgical mishap [3, 9] . The common sites for early post-pancreaticoduodenectomy bleeding could be the suture line of the anastomosis, the pancreatic cut surface, a stress or marginal ulcer, a slipped ligature or a large oozing raw area of the operative site. Therefore, patients with early massive post-pancreaticoduodenectomy bleeding should undergo prompt surgical reintervention until proven otherwise [1, 3, 9] . We propose a management algorithm

for early post-pancreaticoduodenectomy bleeding as shown in figure 3 .

Late post-pancreaticoduodenectomy bleeding is often associated with anastomotic leakage, especially from pancreatic anastomosis, and intra-abdominal infection [1–3, 9, 11, 23, 24] . Approximately two thirds of the re-ported cases of late arterial post-pancreaticoduodenec-tomy bleeding are found to have an underlying fluid col-lection or anastomotic leakage, with a pseudoaneurysm formation identified in approximately one third of the cases [3, 10] . It is hypothesized that late post-pancreatico-duodenectomy bleeding might be caused by erosion of the vasculature resulting from intra-abdominal contam-ination of enteric, pancreatic or bile juice in the area adjacent to the surgical anastomosis [2, 3, 9, 11, 23, 24] . Surgery has always been the treatment of choice for late post-pancreaticoduodenectomy bleeding [10, 25, 26] . However, a surgical approach to late post-pancreaticodu-odenectomy bleeding is often unsuccessful due to severe adhesion, extensive oozing, edematous tissue and inac-cessibility to these vessels, owing to adjacent pancreatic anastomosis [3, 5, 27] . Moreover, suture control of the eroded bleeding vessels is difficult due to local sepsis, se-vere peripancreatic inflammation and friable tissue and vessel walls [3, 27] . Incidence of rebleeding after ligation of the bleeding vessels is as high as 63%, and remains the main cause of death in such patients [3, 20, 27] .

A pretreatment diagnosis would be helpful in the se-lection of the optimal treatment for late post-pancreati-coduodenectomy bleeding [9] , and interventional angi-ography has recently emerged as a safe and effective first-line tool [1–3, 5, 9–11] . Encouraging results have been reported with intravascular intervention as it offers a minimally invasive approach in obtaining hemostasis with a success rate between 63 and 85% [2, 3, 5, 28] . As shown in this study and the literature, the most common site of late post-pancreaticoduodenectomy bleeding is the gastroduodenal artery stump. Its bleeding can be easily detected and effectively resolved by intravascular inter-vention [3, 5, 9, 10, 12, 13, 25] . One would think that an-giography should be the most sensitive and specific diag-nostic test for pseudoaneurysms and late post-pancreati-coduodenectomy bleeding. However, 25% of the bleeders in our post-pancreaticoduodenectomy bleeding cases could not be identified during angiography. It might be hypothesized that there is a clot in the pseudoaneurysm that obscures visualization even when the patient is ac-tively bleeding [9] , or the bleeding is intermittent in na-ture [3] . To improve the identification rate of the gastro-duodenal artery stump during angiography, we routinely

Early PPDB (<1st postoperative day)

Intraluminal Extraluminal

Endoscopy Surgery

PPDB control PPDB not control

Angiography


Surgery

Fig. 3. Management algorithm for early post-pancreaticoduode-nectomy bleeding (PPDB).


Dig Surg 2009;26:297–305304

mark the gastroduodenal artery stump with metallic clips during the pancreaticoduodenectomy. We believe this prevents gastroduodenal artery bleeding from being overlooked, and successful intravascular intervention can still be performed under the guide of clips on the gas-troduodenal artery stump. Our successful experience of intravascular intervention in the patients presenting with sentinel bleeding and rebleeding confirms this policy and encourages us to continue to do so in the future. In agree-ment with other authors [5] , we strongly suggest that an emergency angiography should be considered for all pa-tients who develop either sentinel or massive late post-pancreaticoduodenectomy bleeding, with the added ben-efit that intravascular intervention might prevent the need for a high-risk emergency operation ( fig. 4 ).

Transarterial embolization with a coil occlusion of the CHA may lead to a complete interruption of arterial blood supply to liver, which might result in cholangitis, biliary ischemia, a hepatic abscess or fatal hepatic failure as occurred in 1 of our patients [2, 19, 29] . Our cases also show that the recent use of covered stents may prove to be a successful solution to resolve this issue. A covered stent makes it possible to arrest the bleeding while preserving

the patency of the vessels [3, 10, 12, 15–17] . Potential dis-advantages of the covered stent include a longer duration to achieve hemostasis as compared to transarterial embo-lization, risk of arterial rupture due to low flexibility and fragile vascular walls, and technical difficulties in nego-tiating with torturous arteries [3] .

In conclusion, post-pancreaticoduodenectomy bleed-ing continues to be a potentially lethal complication and is the major cause of surgical mortality after a pancreati-coduodenectomy. Intra-abdominal abscess and anasto-motic leakage, such as pancreatic and gastrojejunostomy leakage, are independent risk factors for post-pancreati-coduodenectomy bleeding. Placement of metallic clips on the gastroduodenal artery stump during a pancreatico-duodenectomy is very helpful in the identification of an overlooked pseudoaneurysm or intermittent sentinel bleeding from the gastroduodenal artery stump during angiography. Although transarterial embolization of the CHA is safe in most patients with gastroduodenal artery bleeding, it cannot guarantee against hepatic failure. The intravascular placement of a covered stent is a preferred solution to avoid a complete interruption of arterial blood supply to liver.

Late PPDB (after 1st postoperative day)

Intraluminal

Endoscopy


Angiography

Surgery


Extraluminal

(either sentinel of massive)

Angiography

Bleeder

visualizable

TAE or covered

stent

Bleeder not

visualizable

Covered stent

at GDA stump

if highly

suspected

Surgery


Fig. 4. Management algorithm for late PPDB.


References

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