Pancreatic Leak Related Hemorrhage

Theodoros Tsirlis, George Vasiliades, Alexandros Koliopanos, Nikolaos Kopanakis,
Anastasia Katseli, Heracles Tsipras, Helias Margaris
Third Surgical Department, “G. Genimmatas” General Hospital. Athens, Greece
ABSTRACT
Context Delayed arterial hemorrhage, secondary to pancreaticojejunal leakage, is an infrequent complication (2-4%) of
pancreaticoduodenectomy but it carries a high mortality rate with more than half of the patients dying from overwhelming sepsis
and/or bleeding. Its ideal management remains unclear. Case reports We hereby present our experience with respect to the
presentation and management of this severe post-pancreaticoduodenectomy complication which occurred in 3/149 patients (2.1%)
operated on between 1996 and 2008 in our department and we review the role of endoscopy, interventional radiology and surgery in
its management. Conclusions The severity of the underlying sepsis and the prompt identification of the sentinel bleed determine
surgical and angiographic intervention and define the outcome in the treatment of a pancreatic leak-related hemorrhage. Endoscopy
has no role in this setting.
INTRODUCTION
Pancreaticoduodenectomy (PD) was historically
considered a formidable procedure with dismal
outcome, although excellent results have been reported
since the 1990’s [1]. Significant progress over the past
two decades with a shift to high volume centers
providing surgical expertise, perioperative care
improvement and interventional radiology modalities
has rendered PD a relatively safe operation with a
mortality rate not exceeding 5%, albeit with a still high
morbidity rate [1, 2, 3, 4, 5].
A delayed hemorrhage, secondary to pancreatic
leakage, is an infrequent (incidence less than 4%)
complication after PD, but one carrying a high
mortality rate, mainly due to septic sequalae. Because
of its rarity and devastating course, hard evidence and a
uniformly accepted treatment algorithm are lacking.
We hereby present our single center experience with
this complication and review possible treatment
strategies.
PATIENTS
From June 1996 through October 2008, 149 patients
(80 males, 69 females; mean age 64 years, range 16-82
years) with a pancreatic head mass underwent a PD in
our department. There were 68 classical Whipple and
81 pylorus-preserving pancreaticoduodenectomies
(PPPDs). The main histological diagnosis was
pancreatic adenocarcinoma in 141 cases and chronic
pancreatitis in 8 cases. Minor morbidity was 40% and
consisted of urinary tract infection, pneumonia,
infection of the surgical wound and delayed gastric
emptying. The overall pancreatic leakage incidence
was 14.1% (n=21) and delayed hemorrhage occurred in
three patients (incidence 2.0%). Postoperative
pancreatic fistulae were classified according to the
International Study Group on Pancreatic Fistula
(ISGPF) definition [2]. We hereby present the case
reports.
Case 1
A 74-year-old female underwent a pylorus-preserving
pancreaticoduodenectomy (PPPD) for a tumor of the
head of the pancreas. The histopathological
examination of the specimen showed chronic
pancreatitis.
Postoperatively, the patient developed a grade A, high
output pancreatic fistula (more than 200 mL/day) due
to a leak from the pancreaticojejunal anastomosis; she
was treated conservatively with TPN and octreotide
analogues. The fistula closed 20 days later without any
additional complications. Three months later, the
patient presented with an episode of macroscopic lower
Received April 25th, 2009 - Accepted June 11th, 2009
Key words Angiography; Pancreatic Fistula; Pancreatico-
duodenectomy; Postoperative Hemorrhage
Abbreviations PD: pancreaticoduodenectomy; PPPD: pylorus-
preserving pancreaticoduodenectomy
Correspondence Theodoros Tsirlis
3rd Department of Surgery, G. Gennimatas Hospital, Mesogeion
Ave154, 11527 Athens, Greece
Phone: +30-210.778.5031; Fax: +30-210.770.6915
E-mail: theotsir@med.uoa.gr
Document URL http://www.joplink.net/prev/200909/04.html

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
493
gastrointestinal (GI) bleeding. Upper GI endoscopy and
colonoscopy did not reveal any pathology. The patient
was transfused with two packs of red blood cells and
was treated conservatively. A few days later, she had a
severe episode of lower GI hemorrhage, and upper
endoscopy showed that the stomach was full of blood
but the source of the bleeding was not identified.
During the endoscopy the patient collapsed and was
urgently transferred to the operating room. An
exploratory laparotomy revealed a small throbbing cyst
which was a pseudoaneurysm of the hepatic artery and
was the source of the bleeding in the lumen of the
intestine. Intraluminal blood was filtered through the
intestinal wall adjacent to the pancreaticojejunal
anastomosis, as the former was part of the
pseudoaneurysm. The pancreaticojejunal anastomosis
had healed and was left intact; the hepatic artery was
dissected and clamped proximally and distally to the
aneurysm. The dissection was possible because the
tissue inflammation had subsided since the
pancreatectomy had been performed three months
earlier. The pseudoaneurysm was opened and the
hepatic artery was identified and meticulously repaired
in an end to end fashion with interrupted fine Prolene®
(Ethicon, Somerville, MA, USA) sutures. We
reinforced the eroded intestinal wall with seromuscular
sutures and an omental patch, and the area was
irrigated and drained. A postoperative angiography
showed a sealed and patent hepatic artery. The patient
recovered uneventfully and was discharged on the 20th
postoperative day.
Case 2
A 65-year-old male underwent a PPPD for a carcinoma
of the ampulla of Vater. The patient developed a grade
B pancreatic fistula, due to a leak of the
pancreaticojejunal anastomosis and was treated
conservatively with TPN and octreotide analogues,
thus achieving a fistula rate of less than 100 mL daily.
On postoperative day 17, the patient became febrile (up
to 38.5°C) and CT of the abdomen revealed an upper
abdominal fluid collection which was successfully
drained under CT guidance. A percutaneous catheter
drain was left in place and clinical and laboratory
improvement of the patient was recorded thereafter. On
day 25, the patient had a mild lower GI bleeding and
was scheduled for upper and lower GI endoscopy while
closely monitored. A few hours later he experienced
severe hematemesis and concurrently collapsed. He
underwent an urgent explorative laparotomy and a
large hematoma was found in the upper abdomen close
to the pancreaticojejunal anastomosis. The source of
the bleeding was the gastroduodenal stump of the
common hepatic artery. Blood entered the lumen of the
intestine through the ruptured pancreaticojejunal
anastomosis where the pancreatic stump was exposed.
The intestinal loop and the pancreatic remnant were
oversewn separately with non-absorbable sutures and
the area was drained with two large bore soft drains.
Due to the patient’s unstable condition and severely
inflamed and distorted tissues, it was not deemed
prudent to proceed with a completion pancreatectomy.
The patient was transferred to the ICU where he
developed septic shock leading to multiorgan failure
and died a few days later.
Case 3
A 51-year-old male underwent a PPPD for a pancreatic
adenocarcinoma. On postoperative day 12, he was
transferred to his residential area hospital in a good
general condition, on a normal diet and with a low rate
pancreatic fistula (less than 75 mL/day) which
discharged through a remaining soft abdominal drain.
Five days later, blood was discharged through the
abdominal drain. The hemorrhage temporarily stopped
and he was hemodynamically stable. He was
transfused, closely monitored and during his transfer
back to our institution, he collapsed and succumbed to
massive hemorrhage through his abdominal drain.
There was no autopsy and, therefore, the precise source
of the bleeding was not clarified.
DISCUSSION
Delayed gastric emptying, pancreaticojejunal failure
and intra-abdominal abscess predominantly account for
the steadily increasing morbidity of PD [2, 3, 4, 5, 6, 7,
8]. Post-pancreatectomy hemorrhage is reported less
frequently with an incidence ranging from 2 to 18%,
nevertheless having conversely high mortality as
compared to other complications with the principal
cause of death being overwhelming sepsis rather than
uncontrolled bleeding [9, 10, 11, 12, 13, 14, 15, 16].
Despite the severity of post-pancreatectomy
hemorrhage, a universal classification system and
treatment practice is lacking. The most systematic
effort in defining post-pancreatectomy hemorrhage
comes from a project of the International Study Group
of Pancreatic Surgery (ISGPS) [17]. According to the
proposed consensus, post-pancreatectomy hemorrhage
should be categorized with respect to time of onset
(early, within 24 h or delayed, post-24 h), location
(intra-luminal or extra-luminal) and severity (grade A,
B or C).
In our series of 149 PDs, there were three cases of
delayed hemorrhage (2.0%). Two patients presented
with intraluminal bleeding and one patient with
sanguineous peritoneal drainage. These three patients
were among the 21 cases (14.1%) with a pancreatic
fistula/abscess due to pancreaticojejunal anastomotic
failure.
Interestingly, hemorrhage occurs in a few cases of
pancreatic leak, although the latter is characterized as
the major risk factor of fatal delayed post-
pancreatectomy hemorrhage. Pathophysiology may
entail the exposure of skeletonized vessels to erosive
enzymes [18], inflammatory or traumatic
pseudoaneurysms [19] and pancreatic pseudocysts
[20]. It can misleadingly manifest as severe upper GI
hemorrhage (Cases 1 and 2), collapse with or without
evident bleeding or as a less dramatic clinical and

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
494
laboratory patient deterioration. The most pivotal sign
is an asymptomatic bloody drain or minor hemoglobin
decrease
in
patients
with
concomitant
pancreaticojejunal leakage complications (Case 3). The
importance of “sentinel bleed” has been emphasized as
a heralding mark for this abdominal catastrophe [16,
21, 22, 23]. Crucial management latency is evident
regarding our Cases 1 and 3. Prompt identification and
treatment with embolization, stenting or surgery is
imperative because it is very unlikely that a patient
with a pancreatic leak-related hemorrhage will be
treated successfully with conservative measures [9,
10].
Endoscopy has been established as the first line
diagnostic option of upper gastrointestinal bleeding,
but its role in delayed post-pancreatectomy hemorrhage
is very limited, if any. Although intraluminal
presentation in the form of hematemesis or melena is
not uncommon [12, 24], appearing in 2 of our 3 cases,
the source of bleeding in this setting is far beyond
endoscopic diagnosis and intervention. Cumulative
experience has made clear that “positive” endoscopic
findings are misleading and delay definitive treatment.
Angiography with subsequent occlusion of arterial
pseudoaneurysms has been widely reported with an
encouraging success rate [13, 23, 24, 25, 26]. The
feasibility and efficacy of transarterial embolization
depends on several factors, such as the patient’s
hemodynamic stability, bleeding etiology, site,
intermittent pattern and institutional facilities and
expertise. As a minimal invasive technique, it may
spare debilitated patients extensive operations; this
rationale is documented by the lower mortality in the
series treated successfully with transarterial
embolization. However, a pancreatic leak-related post-
pancreatectomy hemorrhage is a “secondary”
complication and some form of source-control
intervention is essential. In addition, the occlusive
result of transarterial embolization may have
detrimental effects regarding organ perfusion. Fuji et
al. [27] reported a series of 9 cases treated with super
selective celiac axis transarterial embolization with
44% mortality; 75% of the fatal outcomes were
attributed to ischemic hepatic failure. The report of
Khorsandi et al. with no mortality [24] incorporated
only cases with distal, non-vital vessels. Endovascular
stenting would be an alternative option [28, 29, 30], but
is still technically more demanding.
Surgical exploration is considered to be the gold
standard for post-pancreatectomy hemorrhage and
remains the only option for an unstable, rapidly
deteriorating patient or after failed angiography.
Operative strategy depends on clinical status and
personal experience. Typically, damage control
procedures, including bleeding control and abscess
drainage, pancreatic duct fistulation or completion
pancreatectomy are the cornerstone procedures [31, 32,
33]. In our series, the extent of the local sepsis
determined surgical intervention. Case 1 underwent
successful sutured arterial reconstruction without the
need for pancreaticojejunal breakdown whereas, in
Case 2, only damage control was possible. A
completion pancreatectomy in the latter case might
have had a more favorable outcome, but the patient’s
status and local conditions prohibited it.
Operating on severely ill patients in a difficult surgical
field, with severe inflammation and tissue friability,
accounts for mortality rates which parallel delayed
post-pancreatectomy hemorrhage mortality. Successful
angiography could allow more selective laparotomies
with vascular reconstruction, but relevant evidence is
lacking.
Conclusively, surgical treatment of a pancreatic leak-
related post-pancreatectomy hemorrhage is a salvage
procedure for severely compromised patients and has
high mortality rate. Prompt identification of the
“sentinel bleed” is critical, allowing for minimally
invasive intervention on a still stable patient. Favorable
results of an angiography should be interpreted
cautiously, regarding patient selection and side effects.
Multimodality treatment with ‘on table’ angiography
followed by laparotomy could comprise the ideal
setting. However, close observation, early diagnosis
and aggressive management of pancreatic leakage is
the most effective way to minimize devastating
bleeding complications.
Conflict of interest The authors have no potential
conflicts of interest
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