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Chapter 30 / Liver and Pancreas Transplantation 381
diabetic nephropathy. ese patients are already committed to lifelong
immunosuppression for the renal allograft and therefore only have the added
surgical risk of implanting the pancreas. Simultaneous liver–pancreas and
lung–pancreas transplants have also been reported applying the same phi-
losophy. e kidney and pancreas transplants can be performed either simul-
taneously (simultaneous pancreas and kidney [SPK]) from a single cadaveric
donor or sequentially if a potential living donor can be identied for the kid-
ney allograft (pancreas after kidney [PAK]). A few select centers oer simul-
taneous cadaveric pancreas and living donor kidney transplantation (SPLK).
Less frequently, a pancreas transplant alone (PTA) is oered for di-
cult to control and potentially life-threatening diabe tes mellitus, usually with
documented episodes of hypoglycemia unawareness. In these instances, the
constant risk of untreated hypoglycemia that can result in hypoxic brain
injury, accidents, and mortality outweighs the risk of the procedure and the
immunosuppression. PTA is also oered for recipients who had previously
undergone total pancreatectomy and exhibit poor glycemic control. In these
cases, enteric exocrine drainage has the additional advantage in this recipi-
ent population of restoring exocrine function and improving nutrition.
CONTRAINDICATIONS
Absolute contraindications to pancreas transplantation include substance
or alcohol abuse, uncorrectable cardiac disease, and active malignancy or
infection. Prior to listing, all patients undergo cardiac evaluation, including
a cardiac stress test with coronary angiography investigation of all abnormal
studies. Only candidates with normal or corrected cardiac status are consid-
ered eligible. ere is no specic upper limit for age or body mass index that
contraindicates pancreas transplantation, although these are both features
that may increase the risk of the procedure. Similarly, although not consid-
ered a contraindication, candidates who have undergone extensive prior
abdominal operations or with advanced atherosclerotic arterial disease cer-
tainly present technical challenges that increase the risk of surgery.
SURGICAL TECHNIQUE
Pancreas allografts are procured following an aortic ush with preservation
solution. e spleen is usually retained with the pancreas until implantation
to avoid direct handling of the pancreas. e duodenum is also included
with the allograft in order to facilitate creation of exocrine drainage. e
backbench preparation of the pancreas includes a donor splenectomy and
reconstruction of the donor superior mesenteric and splenic arteries with
a donor iliac artery Y graft. Ultimately, when ready for implantation, the
iliac artery Y graft will serve as the arterial inow and the portal vein the
venous outow.
Pancreas transplantation is usually performed through a midline
incision. SPK transplants are routinely performed with the kidney on the
left and the pancreas on the right, although ipsilateral placement with both
organs on the right side has also been described. Surgical techniques for
pancreas allograft implantation have evolved with time. e original pan-
creas allograft was implanted with a ligated pancreatic duct. e subse-
quent series of transplants were performed with enteric exocrine drainage
and were plagued with early allograft failures because the surgical tech-
niques, organ preservation, and immunosuppression were still in their
infancy. e introduction of bladder drainage of the exocrine secretions
in the 1980s had several advantages over enteric drainage, particularly the
ability to monitor exocrine function by measuring urinary amylase excre-
tion. Furthermore, anastomotic leak from a bladder-drained
p
ancreas
Section IV / Multidisciplinary HPB Care382
is much easier to manage compared to an enteric leak. Unfortunately,
bladder drainage has its own separate list of complications, particularly met-
abolic complications related to the loss of bicarbonate in the urine, cystitis,
urethritis, and reux pancreatitis in recipients with neuropathic bladders.
Recently, as graft survival outcomes following pancreas transplantation
have improved, enteric drainage has become the exocrine drainage proce-
dure of choice at most centers. In fact, it has also become fairly common
for the pancreas to be implanted with the head oriented toward the upper
abdomen in order to facilitate a tension-free enteric anastomosis (Fig. 30.4).
Endocrine graft drainage through the portal vein is most commonly
performed to the systemic venous circulation, usually to the right external
or common iliac veins or vena cava. An alternative technique is mesenteric
drainage through the recipient superior mesenteric vein. Regardless of the
venous outow, the donor iliac artery Y graft is still most commonly anasto-
mosed to the right external or common iliac artery or, less often, the aorta.
e theoretical advantage of mesenteric drainage is that it more closely
imitates the normal endocrine physiology as the insulin is drained directly
into the portal vein, as it is in the native setting. is allows for the rst-pass
FIGURE 30.4 Ipsilateral placement of simultaneously transplanted pan-
creas and kidney allografts. The iliac artery extension Y graft and portal
vein from the pancreas are anastomosed to the recipient common iliac
artery and vein, respectively.
Chapter 30 / Liver and Pancreas Transplantation 383
eect through the liver, where approximately half of the insulin is removed
resulting in relatively lower systemic insulin levels. Both endocrine drain-
age techniques establish normoglycemia, although with dierent systemic
insulin levels, and similar graft and patient survival.
Immunosuppression
A detailed discussion of immunosuppression is beyond the scope of this chap-
ter, but some highlights are provided. e most common protocols include
induction immunosuppression with depleting antibodies such as alemtu-
zumab (Campath), a monoclonal antibody to CD52, or rabbit antithymocyte
globulin (ymoglobulin). Maintenance immunosuppression most com-
monly includes a combination of tacrolimus and mycophenolate mofetil or
sirolimus. It has also become a relatively common practice to avoid steroids as
maintenance immunosuppression. In addition to the toxicities of the various
immunosuppression agents, there is also an associated risk for opportunistic
infections, particularly CMV and BK virus in kidney and pancreas transplant
recipients, and opportunistic malignancies such as skin cancers and lym-
phoma (including PTLD). Prophylaxis against CMV and Pneumocystis jiroveci
is routinely required following induction immunosuppression.
COMPLICATIONS
Technical failure, dened by the International Pancreas Transplant Registry
as graft loss secondary to vascular thrombosis, bleeding, anastomotic leaks,
or infection/pancreatitis, is responsible for more than half of all pancreas
grafts lost in the rst 6 months following transplantation, representing
approximately 8% to 10% of transplants. rombosis accounts for more than
half of these technical failures and may be inuenced by donor and recipient
factors, preservation and ischemic injury, immunologic issues, and surgical
technique. Timely re-exploration is critical because, if there is indeed vascu-
lar thrombosis, the resulting allograft inammation may initiate a systemic
response with consequent recipient hemodynamic compromise or seg-
ments of the clot may form pulmonary emboli if the portal vein is systemi-
cally drained. Additionally, if explored early enough, vascular thrombectomy
with graft salvage is occasionally possible. In cases where allograft pancre-
atectomy is required, immediate retransplantation is an option that oers
the motivated patient an opportunity to regain the benets of a functional
allograft.
Postoperative hemorrhage can present with intraperitoneal bleeding
from the pancreas allograft or retroperitoneum or with gastrointestinal
bleeding at the site of an enteric anastomosis. If the enteric anastomosis is
created at the level of the proximal jejunum, this is approachable endoscop-
ically and can often be treated without returning to the operating room. It is
a good practice to intubate the recipient prior to push enteroscopy in order
to protect the airway. In the event of severe gastrointestinal bleeding for
which angiography is considered, it is essential that it be communicated to
the interventional radiologist that the iliac arteries be interrogated in addi-
tion to the mesenteric vessels as the donor duodenum or an arterioenteric
stula may be the source of bleeding. An option to manage severe bleeding
from the pancreas allograft endovascularly is placement of a covered stent
in the recipient iliac artery to totally bypass the takeo of the donor artery
prior to emergency laparotomy and accept the loss of the pancreas allograft
in the event of life-threatening bleeding.
As with other pancreatic operations and enteric anastomoses,
enteric or pancreatic leaks may develop and usually present with an
abscess or
f
istula. Options for management include operative and
Section IV / Multidisciplinary HPB Care384
percutaneous drainage. A drained abscess or fistula with low output
will usually heal with time, although if the uid collects around the area
of the vascular anastomoses, it may predispose to the formation of arte-
rial pseudoaneurysm. A high index of suspicion is required to diagnose
and treat this life-threatening complication; any bleeding into an abscess
drain should be presumed to represent a herald bleed until pseudoaneurysm
is ruled out radiologically. Pseudoaneurysms can be managed endovas-
cularly, and graft salvage, although uncommon in this setting, has been
described.
Small bowel obstruction (SBO) can complicate any laparotomy. In
addition to adhesions, two etiologies of SBO are specic to pancreas trans-
plantation. First of all, the enteric anastomosis, particularly when the pan-
creas is oriented with the head upward, creates an internal hernia defect
that is prone to incarceration and intestinal volvulus if not specically
closed at the time of transplantation (Fig. 30.5). Second, the anterior sur-
face of the pancreas in the retroperitoneum presents a raw surface that is
prone to adhesion formation. It is our own practice to cover the pancreas
with a sheet of adhesion barrier at the end of the operation. Similarly, the
FIGURE 30.5 Internal herniation of the small intestine behind the pancreas allograft
through a defect created at the time of transplantation. The opening is dened by the aorta
and iliac artery posteriorly, the small bowel mesentery superiorly, the pancreas and enteric
anastomosis anteriorly, and the pancreatic vascular anastomoses inferiorly.
Chapter 30 / Liver and Pancreas Transplantation 385
intraperitoneal renal allograft should be covered with colon in order to
p
revent contact with the small intestine.
OUTCOMES
In the United States, approximately 1,200 to 1,500 pancreas transplants
are performed annually. SPK makes up the majority of the pancreas trans-
plants performed, accounting for approximately two-thirds of the total.
Patient survival is currently similar for all three categories of pancreas
transplantation, approximately 96% at 1 year (Fig. 30.6). Pancreas allograft
survival has historically been superior for SPK compared to isolated pan-
creas transplantation (85% vs. 78% at 1 year) (Fig. 30.7). e dierence in
graft survival is often attributed to increased immunologic pancreas graft
loss in isolated pancreas allograft recipients (PAK and PTA) compared to
SPK recipients (5% vs. 2% at 1 year). is increased pancreas graft loss to
rejection has been attributed to delayed detection and initiation of treat-
ment for rejection because these recipients lack the early warning of a
deterioration in renal function, which may be considered a harbinger of
pancreas rejection in SPK recipients. Recent data from large centers using
depleting antibody induction and steroid-free maintenance immuno-
suppression protocols suggest that we have entered a new era of immu-
nosuppression where immunologic graft loss is becoming an infrequent
occurrence. With this cause of graft failure practically eliminated, it is
likely that pancreas allograft survival in isolated pancreas transplantation
will begin to approach that of SPK. In fact, in the most recent update of
the International Pancreas Transplant Registry, the 1-year graft survival for
all three categories of pancreas transplantation was similar at 89% to 90%
for programs using anti–T-cell antibody induction and maintenance with
tacrolimus and sirolimus.
0
60
70
80
90
Months Posttransplant
612182430
3/11
36
PTA 433 96.4%
Category n 1Yr Surv.
PAK 800
96.0%
SPK 4,129 95.8%
100
USA primary DD pancreas transplants 1/1/2006 – 12/31/2010
Patient survival
%
I
P
T
R
/UNOS
FIGURE 30.6 Patient survival following primary deceased donor pancreas transplanta-
tion in the United States between 1/1/2006 and 12/31/2010. Pancreas transplants are
categorized by type as pancreas transplant alone (PTA), pancreas after kidney (PAK), and
simultaneous pancreas and kidney (SPK). (Reprinted with permission from the International
Pancreas Transplant Registry.)
Section IV / Multidisciplinary HPB Care386
Suggested Readings
Liver Transplantation
Abu-Elmagd K, Fung J, Bueno J, et al. Logistics and technique for procurement of intestinal,
pancreatic, and hepatic grafts from the same donor. Ann Surg 2000;232(5):680–687.
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;
357(25):2601–2614.
Hong JC, Yersiz H, Farmer DG, et al. Longterm outcomes for whole and segmental
liver grafts in adult and pediatric liver transplant recipients: a 10-year comparative
analysis of 2,988 cases. J Am Coll Surg 2009;208(5):682–689; discussion 689–691.
Mangus RS, Fridell JA, Vianna RM, et al. Immunosuppression induction with rab-
bit anti-thymocyte globulin with or without rituximab in 1,000 liver transplant
patients with long-term follow-up. Liver Transpl 2012;18:786–795.
Tector AJ, Mangus RS, Chestovich P, et al. Use of extended criteria livers decreases
wait time for liver transplantation without adversely impacting posttransplant
survival. Ann Surg 2006;244(3):439–450.
Pancreas Transplantation
Fridell JA, Johnson MS, Goggins WC, et al. Vascular catastrophes following pancreas
transplantation: an evolution in strategy at a single center. Clin Transplant 2011;
DOI: 10.1111/j.1399-0012.2011.01560.x.
Fridell JA, Mangus RS, Hollinger EF, et al. e case for pancreas after kidney transplan-
tation. Clin Transplant 2009;23(4):447–453.
Fridell JA, Mangus RS, Mull AB, et al. Early reexploration for suspected thrombosis
after pancreas transplantation. Clin Transplant 2011;91:902–907.
Fridell JA, Powelson JA, Sanders CE, et al. Preparation of the pancreas allograft for
transplantation. Clin Transplant 2011;25(2):E103–E112.
Fridell JA, Rogers J, Stratta RJ. e pancreas allograft donor: current status, controver-
sies, and challenges for the future. Clin Transplant 2010;24(4):433–449.
Gruessner AC, Sutherland DE, Gruessner RW. Pancreas transplantation in the United
States: a review. Curr Opin Organ Transplant 2010;15(1):93–101.
Humar A, Kandaswamy R, Granger D, et al. Decreased surgical risks of pancreas trans-
plantation in the modern era. Ann Surg 2000;231(2):269–275.
0
3/11
6
Cat. n1Yr Fxn
12 18
Months posttransplant
I
P
T
R
/UNOS
24 30
p £ 0.0001
36
100
%
USA DD primary pancreas transplants 1/1/2005 – 12/31/2010
80
60
40
20
SPK 4,122 85.5%
PAK 798 79.9%
PTA
SPK
PAK
PTA
433 77.8%
0
Pancreas graft function
FIGURE 30.7 Pancreas allograft survival following primary deceased donor pancreas
transplantation in the United States between 1/1/2005 and 12/31/2010. Pancreas trans-
plants are categorized by type as simultaneous pancreas and kidney (SPK), pancreas after
kidney (PAK), and pancreas transplant alone (PTA). (Reprinted with permission from the
International Pancreas Transplant Registry.)
387
Radiology oers many imaging modalities for evaluation of diseases in the
abdomen; some include ultrasound, computerized tomography (CT), mag-
netic resonance imaging (MRI), positron emission tomography (PET) scan,
and nuclear medicine. e choice of appropriate imaging modality should
be made on an individual case basis depending on the lesion under ques-
tion, availability of imaging facilities, and cost issues. Choosing the most
appropriate imaging modality for evaluating the lesion under question
depends on the information required from imaging for clinical manage-
ment decisions. For example, while ultrasound might be an appropriate
examination for a patient with no prior medical history and increased
alkaline phosphatase and bilirubin levels, ultrasound is not an adequate
screening test for hepatocellular carcinoma in a patient with cirrhosis and
increased alpha-fetoprotein. Similarly, while multidetector CT (MDCT)
serves as the rst-line imaging modality for evaluation of liver, MRI oers
an attractive radiation-free option with superior soft tissue contrast dier-
entiation. e clinical applications and ben et of MRI are rapidly expanding
due to new sequences and contrast agents. However, in most centers, MRI is
still reserved as secondary imaging modality, with such indications as char-
acterization of incidental liver lesions detected on CT or for patients with
iodinated contrast allergy.
LIVER
Ultrasound
Sonography is a safe, noninvasive, quick, and inexpensive means of eval-
uating the liver. It can be performed at the bedside, needing little patient
cooperation. e liver is ideally examined following a 6-hour fast so that
gallbladder is not contracted. e normal tissue texture of the liver is
homogeneous with ne echoes that appear as moderately short dots or
lines. Abnormal parenchymal echogenicity is judged by comparing it to
the right renal cortex. Increased echogenicity of the liver usually indicates
hepatosteatosis. Ultrasound has good sensitivity for detection of focal liver
lesions; however, specicity is not very high.
Duplex and color ow Doppler imaging improve the diagnostic capa-
bilities of ultrasound by enabling the evaluation of complex circulatory
dynamics of liver. rombosis, reverse ow, aneurysms, and stulas are
demonstrated with duplex and color ow Doppler. But color Doppler stud-
ies are usually unable to evaluate the vascularity of the liver neoplasms due
to low intensity of the signals.
In liver transplant recipients, survival of the allograft depends on
patency of the hepatic artery. Changes in the normal hepatic artery wave-
form may suggest stenosis or thrombosis in these patients. Liver transplant
patients require very close follow-up for vessel patency during the immediate
postoperative period.
HPB Imaging (Including IR,
Ultrasound, MRI, CT, Nuclear
Medicine)
Temel Tirkes and Kumaresan Sandrasegaran
31
Section IV / Multidisciplinary HPB Care388
Intraoperative Ultrasound
Acoustic attenuation by subcutaneous fat somewhat degrades the images
of the transabdominal ultrasound. During intraoperative ultrasound, a
high-frequency probe is directly placed on the liver surface, providing high-
resolution images. e most common application of intraoperative ultra-
sound is during surgery in patients undergoing segmental resection for
hepatic metastases. Intraoperative ultrasound can detect even the minute
liver lesions and modify the surgical management of patients . Intraoperative
ultrasound has been more widely utilized across the spectrum of HPB
surgery (see Chapter 12).
Computed Tomography
Advances in MDCT enabled very fast scan times and improved resolution
due to isotropic image acquisition. e goal of contrast enhancement is to
improve lesion visibility by increasing the relative attenuation dierence
between the lesion and normal hepatic parenchyma. A routine contrast-
enhanced CT of the liver is performed during the portal phase and is usu-
ally sucient for detection and follow-up of most hypovascular metastatic
liver lesions. Multiphasic CT is performed in the arterial, portal venous,
and delayed phases. During arterial phase, hypervascular lesions including
hepatocellular carcinoma and metastases from renal, breast, carcinoid, and
pancreatic islet cell tumors enhance earlier than the normal liver paren-
chyma. ese lesions may become isodense to liver parenchyma during
portal venous or delayed phase. Some hypervascular lesions show lower
density during portal or delayed phase called “washout” phenomenon.
Detection of a hypervascular lesion that shows washout is commonly seen
in cirrhotic patients with hepatocellular carcinoma. Delayed scanning has
been employed to improve detection of intrahepatic cholangiocarcinoma
and hepatocellular carcinoma.
Noncontrast CT scan of the liver is inferior to contrast-enhanced stud-
ies for lesion detection and is not routinely performed except in certain
specic situations. Patients with liver disorders that diusely alter hepatic
attenuation, such as hepatosteatosis, hemochromatosis, and amiodarone
toxicity should be evaluated with noncontrast CT. Noncontrast liver CT
may be indicated for evaluation of calcied lesions calcication (such as
metastases from mucinous colon carcinoma), or hemorrhage (in lesions
like hepatocellular adenomas).
Magnetic Resonance Imaging
e recent development of rapid acquisition techniques with excellent
image quality and tissue-specic contrast agents has made MRI the most
accurate imaging modality for the evaluation of liver disease (Fig. 31.1).
Traditionally T1- and T2-weighted sequences were performed with sup-
pression of the body fat; however, many novel pulse sequences are being
developed to decrease scan time and increase signal-to-noise ratio. MRI is
often superior to CT or ultrasound in lesion characterization but usually
reserved as a second-line modality secondary to cost.
Magnetic resonance contrast agents are crucial in liver lesion detec-
tion and characterization. ere are many MR contrast agents with dierent
properties. Examples of extracellular contrast agents include the gadolinium
chelates, gadopentetate dimeglumine (Gd-DTPA) and gadoterate meglu-
mine (Gd-DOTA). ese agents function similar to iodinated CT contrast
agents by rapidly diusing from the intravascular space to the extracellular
space. Hepatobiliary specic agents such as gadoxatate (Gd-EOB-DTPA)
and gadobenate dimeglumine (Gd-BOPTA) increase the signal intensity of
the normal liver and hepatocyte-containing lesions such as focal nodular
Chapter 31 / HPB Imaging (Including IR, Ultrasound, MRI, CT, Nuclear Medicine) 389
FIGURE 31.1 Hepatocellular carcinoma visualized by multiphasic contrast-enhanced MRI
of the liver. A. Arterial phase of the study shows a mass within the left lobe of the liver
enhancing earlier than the rest of the liver parenchyma (arrow). Note the prominent intra-
tumoral arterial network. B. Portal venous phase of the examination shows that the mass is
relatively hypervascular (arrow) compared to the surrounding liver parenchyma.
(Continued)
Section IV / Multidisciplinary HPB Care390
hyperplasia. is increased signal intensity improves the contrast dierence
between the liver parenchyma and nonhepatocellular lesions (such as metas-
tases) during the delayed phase images.
Positron Emission Tomography Scan
e liver demonstrates diusely increased udeoxyglucose (FDG) activ-
ity physiologically and is used as a qualitative comparison point for other
foci of uptake in the body (e.g., pancreatic and gallbladder lesions). Activity
that is equal to or greater than that in the liver raises concern for patho-
logic processes. Overall, most metastatic tumors are FDG avid and readily
detectable using PET–CT. FDG-PET imaging of hepatocellular carcinoma
is somewhat limited due to the activity of glucose-6-phosphatase, which is
found in varying degrees in this tumor. Hepatocellular carcinoma is more
FDG avid than the liver in approximately 55% of cases; it is equal to or less
avid in 30% and 15% of cases, respectively. Generally, PET detects only 50%
to 70% of hepatocellular carcinomas, but is useful in detection of distant
metastases (extrahepatic disease) as well as in evaluation of recurrence. In
FDG avid hepatocellular carcinoma, PET–CT imaging is helpful for staging,
especially in the assessment of distant metastatic disease.
GALLBLADDER
Ultrasound
Real-time transabdominal sonography is the most widely used diagnostic
examination for the gallbladder since it is quick and easy to perform. e
gallbladder is visible on sonograms in virtually all fasting patients despite
FIGURE 31.1 (Continued) C. Delayed phase of the study shows that enhancement char-
acteristic of the mass has excreted the contrast earlier than the liver parenchyma and
now shows relatively less enhancement (arrow). Early contrast uptake and early con-
trast clearance is called “washout phenomenon” and is a characteristic of hypervascular
malignancies.