A 56-year-old female patient presented to the
emergency department of our hospital complaining about poor general condition and melena. On
her physical examination, the blood pressure was
85/50 mmHg and pulse 115/min. No abdominal
pain or tenderness was noted. Hemoglobin level
was 8.4 mg/dL in the initial complete blood count
analysis and 8 mg/dL in the next control carried
out 1 h later. Her medical history revealed a
history of total abdominal hysterectomy + bilateral
salpingo-oophorectomy four years ago. Abdominal
ultrasound did not reveal any signs compatible with
her complaints and there was no need for emergency
colonoscopy and sigmoidoscopy. On abdominal CT,
free air was detected in the paraaortic area adjacent
to the posterior third part of the duodenum and
reduction in the fat plane between the third part of
the duodenum and the aorta. Since hyperdense areas
suggesting hematoma were also found in the second
part of the duodenum, and the patient was assessed
for an AEF. A written informed consent was obtained
from the patient and she was urgently operated. During the operation, retroperitoneum was opened
previously, and an AEF was observed to develop in
this region between the third part of the duodenum
and the left proximal end of the iliac artery. The
duodenum was detached and was primarily repaired.
The iliac artery was fixed at the proximal and distal
parts of the fistula. Then, a suprapubic graft was
placed between the right and left femoral artery. The
operation was completed in this way; however, since
the intestinal content was running from the drains on
postoperative Day 4, she was reoperated. The patient
was administered intestinal resection and bypass
and no other problems occurred during follow-up.
When the gynecology department was consulted,
the patient was learnt to previously undergo a
retroperitoneal lymph node dissection in this region
during the initial gynecological surgery. The patient
is still alive without any complications at 15 months
of her follow-up.
Description
An AEF is an open connection developed between
the aorta or its major branches and GI tract. It
can develop without any prior aortic intervention,
which is called primary AEF (PAEFs), and the
first case was published by Salmon in 1843.[2] Its
prevalence is between 0.04 and 0.07% in the general
population.[3] The PAEFs usually occur between
an aneurysmal aortic segment and an adjacent GI
structure (73 to 88%); however, they can also develop
due to tumors, infections, radiotherapy, peptic ulcers,
inflammatory intestinal diseases, and foreign objects
without the presence of an aneurysm.[4] A fistula
between a vascular prosthesis placed during an aortic
surgery and any part of the GI tract is called a
secondary AEF (SAEF), which was first described by
Brock in 1953.[5] These are more common compared
to PAEFs with a reported incidence between 1.6
and 2% after an aortoiliac surgery.[6,7] Its incidence
may increase up to 14% after an emergency rupture
aneurysm surgery where bacterial contamination and
iatrogenic intestinal injuries are more likely.[8]
The SAEFs usually develop due to continuous
physical stimulation or infection occurring during an
index aortoiliac reconstructive surgery. However, they
can also occur in rare cases due to interventions to the
aorta or its major branches during surgical procedures
performed for other purposes.[9] Another condition
which extremely resembles SAEFs, is aortoenteric
erosion (AEE). In AEE, the vascular prosthesis leads to erosion on the outer layers of a neighboring GI
structure, causing intestinal mucosa to surface. There
is a contact between the intestinal mucosa and the
prosthetic graft body, but no fistulization. The graft
wall is strong enough to prevent any blood passage
from the vascular compartment to the GI lumen. The
bleeding in AEE usually originates from the intestinal
mucosa. In true SAEFs, however, the contact is
between the intestine and the anastomotic margin of
the graft, which is usually the proximal anastomotic
line.[1] The distinction between these two entities is
nothing, but a matter of definition. Since the treatment
and clinical course of both conditions are almost
the same, publications usually address into these
two conditions under the same topic. Although the
mechanism leading to AEFs has not been elucidated
fully, it is thought that the constant pulsatile trauma
exerted by the aneurysmal sac to the adjacent structure
leads in time to erosion and fistulization in PAEFs.
For SAEFs, the agents penetrating the locus from
enteric structures that erode through chronic pulsatile
stimulus of the prosthetic object and its anastomosed
lines or the infection caused by the graft contaminated
during the initial surgical intervention are thought
to play a key role in the development of a fistula.
The inflammation resulting from infection leads to
pseudoaneurysms in the anastomotic region, which
is the most sensitive part of the vascular structure,
followed by formation of a fistula.[3,9-12] The iatrogenic
traumas occurring in the intestinal structures during
surgery should be also considered in the etiology.
Although AEFs can occur anywhere along the
GI tract, more than half of them are seen in the
duodenum. The most commonly involved section of
the duodenum is its third part.[13] This retroperitoneal
part of the duodenum has a fixed location between
the Treitz ligament, aorta, and superior mesenteric
artery. The closeness of this transverse part of the
duodenum to the aorta and proximal anastomosis of
the graft makes the duodenum more susceptible to
AEF development.
Signs and symptoms
Due to the relationship of AEFs with vascular
and intestinal lumens, the most expected symptom
in these patients is GI bleeding. A large majority
of the patients present with hematemesis (54%)
and melena (41%), while other common symptoms
are abdominal pain (21%), sepsis (12%), and fever
(11%).[13,14] The triad of GI bleeding, abdominal pain, and pulsatile mass in the abdomen, which was defined
by Cooper[15] approximately 200 years ago and agreed
to be pathognomonic for PAEF, is seen only in 11%
of the patients.[13] Patients with PAEFs and SAEFs
usually have the same clinical signs. One of the major
characteristics of these patients is that they usually
have a herald bleed before the massive GI bleeding
occurs. This herald bleed which happens hours or
days before the life-threatening bleeding is mostly
self-limiting.[16-18] This limitation is thought to be
associated with the thrombus forming in the relatively
small fistula in the patient who becomes hypotensive
due to bleeding. In the following days and hours,
this thrombus leaves its place and abundant bleeding
starts to take place. Therefore, it is important to avoid
aggressive fluid replacement at the time of hospital
admission and to keep the systolic blood pressure
in the 70 to 100 mmHg interval. In addition, signs
of sepsis such as fever, leukocytosis, weakness, and
bacteremia are seen in 41%, shock in 46%, and pain in
22% of the patients.[19]
Diagnosis
The most important step in diagnosing AEFs is to
keep the suspicion of an AEF in mind. Since AEFs
are less common among the causes of GI bleeding,
clinicians may not be knowledgeable enough on this
pathology, and the signs and symptoms quite differ
from case to case, and the sensitivity of imaging
methods are relatively low, and the diagnosis is often
missed. Therefore, if a patient who presented with
complaint of GI bleeding has an aortic aneurysm or a
previous aortoiliac surgery, he/she should be considered
to have an AEF, until otherwise evidenced.[20] Even if
no active bleeding is found in physical examination,
such patients should be closely observed and their
vital signs continuously monitored, as they usually
experience a herald bleed before the onset of their
abundant bleeding.[16,17] Currently, the most commonly
used imaging method is CT.[21,22] As it is readily
available, has relatively easy application and short scan
time, and gives a lot of information for the differential
diagnosis, CT is the most suitable diagnostic tool
for the diagnosis of AEFs. The most important CT
finding in AEFs is the gas detected in the aorta or
in adjacent regions.[23] However, the presence of gas
is not specific to AEF alone. It is normal to find free
gas in this region within the first month following
an aortoiliac surgery. Gas in this region can be also
detected in graft infections without the presence
of a fistula. However, any soft tissue, gas or fluid to be found around the graft after Week 7 should
be considered as a perigraft infection.[24] The most
specific indication is the contrast penetration from the
aorta into the intestinal lumen, although this can be
detected rarely.[25,26] Penetration of free contrast from
the aorta to the surroundings of the graft is again a
specific finding; however, this is also encountered
quite rarely. Non-specific signs much more commonly
found than the aforementioned findings are more
useful in making the diagnosis of an AEF. The most
frequent signs indicating an AEF include reduced
periaortic fat plane, focal thickening, and shrinkage in
the neighboring intestinal wall, periaortic free fluid,
free gas around the aorta, and pseudoaneurysm at the
anastomotic margin.
Although the diagnostic value of
gastroduodenoscopy varies in different publications,
it can diagnose 25 to 50% of all AEFs.[27] A large
majority of AEFs are seen in the third and fourth
parts of the duodenum, which makes it technically
difficult to advance the endoscope to this region and
requires synchronization between operator and patient.
Nevertheless, gastroduodenoscopy is quite helpful in
differentiating from other causes of GI bleeding.[27]
It gives fairly specific results in terms of scintigraphy
and 18F-fludeoxyglucose (FDG) positron emission
tomography (PET)/CT AEF. However, it is not much
practical, since the patient must be in a stable position
during the scan. Due to its less availability and longer
scan time, magnetic resonance imaging (MRI) is not
a highly preferred imaging method in AEFs, yet.
Although not primarily a diagnostic tool for AEFs,
conventional angiography can be used in patients
who are eligible for transcatheter and endovascular
interventions.
Treatment
Once diagnosed with an AEF, the patient should
be started an empirical antibiotherapy without any
delay. Microorganisms of different species are isolated
in PAEFs.[3,13,27] One of the most frequently isolated
microorganisms is Candida.[19] As for bacteria, the most
commonly isolated species are Escherichia coli, E. faecalis,
Salmonella, Mycobacterium tuberculosis, Clostridium
septicum, Lactobacillus, and Klebsiella.[28] However, very
few studies provide data on the culprit microorganism.
Although studies on SAEFs have reported isolation
of many different microorganisms, most of the cases
involve Staphylococcus, Streptococcus spp. and Escherichi
coli.[28] Apart from these, Pseudomonas aeruginosa, Enterococcus spp., Veilonella spp., Peptostreptococcus spp.,
E. Coli, and Staphylococcus aureus have been identified
in the mixed flora.[28] Patients diagnosed with an AEF
should be immediately started antimicrobial therapy
in the postoperative period. The treatment should
involve broad-spectrum antibiotics and antifungals
covering Gram-positive, Gram-negative, and anaerobic
pathogens, as well as Candida.
Patients in whom antibiotherapy is arranged should
be made ready for a surgical intervention without
losing time. Even if they are hemodynamically stable
at the time of admission, it should be kept in mind
that these patients may have abundant bleeding at
any time. The liquid and blood needs of patients who
are unstable or in shock should be met immediately.
Afterwards, an intervention method suitable for the
patient should be selected. Open surgery is a widely
used and recommended treatment; however, there are
ongoing works on endovascular intervention which has
become increasingly popular recently.
ISB versus EAB
The AEFs are conditions which result in death, if
left untreated. Since it was first defined, AEFs have
been evidenced to require surgery for treatment. The
main goal of open surgery is to ascertain the diagnosis,
stop bleeding, remove the infected graft, resect the
infected tissues as broadly as possible, repair intestinal
defect, and allow the blood flow to the distal vascular
bed through a vascular prosthesis. Therefore, the EAB
method has been used for the treatment of AEFs since
early periods, in which the vascular prosthesis is placed
away from the infected region. This approach has been
agreed to be the gold standard for a long time, but
it is not possible to advocate that the results are at a
desired level. Several studies have reported mortality
rates between 25 and 90% for EAB, major amputation
rates between 5 and 25%, and aortic stump rupture
rates between 10 and 50%.[9] Since the prolonged
surgical time of EAB causes a serious stress in patients
with an already poor general condition, the idea of a
staged surgery has emerged. In patients with a stable
condition, first a lower extremity blooding is achieved
through EAB and, in the following days, AEF repair
and graft excision are performed. This approach aims
at reducing mortality. In a study including patients
with aortic graft infection, postoperative mortality
was found to decrease to 11%.[29] Many centers have
attempted ISB using an infection-resistant graft after
removing the infected graft for having a low long-term graft patency, lacking the desired low reinfection rates,
and having the risk of aortic stump blow-out. The
Texas Houston University has started using ISB for
treating AEFs and many researchers have utilized ISB
technique using a variety of conduits.[30] In general,
prosthetic grafts, cryopreserved grafts, and autologous
venous grafts are used for ISB.
Prosthetic grafts have become more favorable over
time owing to their low cost and easy availability
in various sizes, even in emergency cases. Those
prosthetic grafts soaked with rifampin or amikacin
or coated with silver to increase their resistance to
infections are more preferable. However, there are
controversial results with antibiotic-soaked grafts.[31]
Grafts soaked with rifampin yield the best outcomes
in terms of amputation, conduit failure, and early
mortality, although they have the highest reinfection
rate.[31] In addition, clinical studies have shown that
these grafts are ineffective against methicillin-resistant
bacteria such as Staphylococcus aureus and Escherichia
coli.[32] Owing to their silver ion contents, silver-coated
grafts are believed to show antimicrobial effects
by inhibiting deoxyribonucleic acid replication and
protein transcription of messenger ribonucleic acid
inside bacterial cells. Although silver-coated grafts
have been shown to fail in preventing infections in the
in vitro setting, some authors have reported promising
results.[33,34] Another disadvantage of the prosthetic
grafts is their high graft failure and occlusion rates.[35]
Another graft used for ISB is the autologous
saphenous graft. Also known as the neoaortoiliac
surgical reconstruction, this method aims at
restructuring the superficial femoral veins of the lower
extremities to make them resistant to aortoiliac system
infections. Kakkos et al.[36] found in their study that
ISB procedures where lower extremity femoral veins
were used had lower mortality rates than the procedures
using other grafts. The most favorable outcomes
regarding the reinfection rate were also found to be
associated with autologous vein grafts.[34] Extremity
complications such as edema and compartment
syndrome associated with the use of lower extremity
deep veins were found within acceptable limits, while
only 2% of patients had fasciotomy-requiring edema
and permanent leg edema.[37] Since removal of femoral
veins takes a long time and prolongs the duration
of surgery, it should not be used in patients whose
condition is critical, nor should it be used in those
having a history of prior deep vein thrombosis.[38]
Although many publications report favorable outcomes with autologous vein grafts, in their 50-case series
where they used femoral vein in 34 cases, Chopra et
al.[39] reported that the 30-day and 60-day mortality
rates were 25% and 48%, respectively.
The results of intestinal repair are independent risk
factors affecting survival. Contrary to vascular approach,
there is a consensus on intestinal repair. Minor intestinal
defects can be repaired outright. In larger defects,
however, complex surgeries should not be avoided in
fear of leakage and reinfection.[40] Since mortality from
reinfection is 100%,[19] it is of vital importance to repair
any intestinal leakage most effectively during the first
session. Emergence of intestinal complications shows a
homogeneous distribution within the first 60 days with
an apparent decline, thereafter. Thus, caution should be
exercised during the first 60 days for early mortality in
AEF cases.[38]
Endovascular repair
In recent years, many studies have been published
regarding the outcomes of endovascular intervention
in AEFs.[36,41] This approach has been used more
frequently in patients who are ineligible for open
surgery due to anatomic inconvenience or poor general
condition. This method allows a much less invasive
approach to closure of the fistula and prevention
of bleeding. However, contrary to open surgery, it
makes no contribution to the treatment of infection.
Therefore, a serious risk of infection continues for
the newly placed endovascular prosthesis. Review of
the literature on EVAR results reveals a significant
superiority to open surgery in terms of early mortality,
but such a superiority disappears in the follow-up
period.[36] As endovascular treatment does not involve
intestinal repair, it should not be considered as a
destination treatment. In a 13-month follow-up study,
Antoniau et al.[42] reported reinfection and bleeding
in 44% of the patients who were administered EVAR
for AEFs. In ineligible patients, therefore, EVAR
should be considered as a bridging treatment, until the
patient becomes ready for open surgery, which should
be administered as soon as the patient becomes eligible
for it. However, used as the first-line treatment, EVAR
may render in situ repair more complicated. Moreover,
since the fistula originates mostly from proximal
anastomosis, insertion of an endograft may pose a risk
for the perfusion of renal arteries.
In conclusion, an AEF is a complication resulting
in death, if left unrepaired. It should be kept in mind
that patients who present in a stable condition may
be lost due to abundant bleeding at any time; thus, a surgical intervention should be performed as soon
as possible. The AEB, which has been agreed to
be the gold standard in the treatment of AEFs for
a long time, is now being replaced by ISB thanks
to its superior results in the recent publications. Of
note, no consensus has been reached yet for the grafts
to be used for ISB, and none of the currently used
grafts has produced a desirable outcome. Endovascular
interventions which have become increasingly popular
in recent years should be only used for bridging to
open surgery. Performing an intestinal repair in a safe
way is of vital importance. Successfully treated patients
should be very closely monitored for the first 60 days
for possible reinfection and bleeding.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect
to the authorship and/or publication of this article.
Funding
The authors received no financial support for the research
and/or authorship of this article.