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Chapter 29 / Bile Leak and Bile Duct Injury 371
Melton GB, Lillemoe KD, Cameron JL, et al. Major bile duct injuries associated with
laparoscopic cholecystectomy: eect of surgical repair on quality of life. Ann Surg
2002;235:888.
Pitt HA, Sherman S, Johnson MS, et al. Improved outcomes of bile duct injuries in the
21st century. Ann Surg 2013;258:490.
Sheeld KM, Riall TS, Han Y, et al. Association between cholecystectomy with vs
without intraoperative cholangiography and risk of common duct injury. JAMA
2013;310:812–820.
Sicklick JK, Camp MS, Lillemoe KD, et al. Surgical management of bile duct injuries
sustained during laparoscopic cholecystectomy: perioperative results in 200
patients. Ann Surg 2005;241:786.
Stewart L, Way LW. Bile duct injuries during laparoscopic cholecystectomy: factors
that inuence the results of treatment. Arch Surg 1995;130:1123–1129.
Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during
laparoscopic cholecystectomy. J Am Coll Surg 1995;180:101.
Strasberg SM. Biliary injury in laparoscopic surgery: Part 2. Changing the culture of
cholecystectomy. J Am Coll Surg 2005;201:604.
Walsh RM, Henderson JM, Vog t DP, et al. Long-term outcome of biliar y reconstruction
for bile duct injuries from laparoscopic cholecystectomies. Surgery 2007;142:450.
Way LW, Stewart L, Gantert W, et al. Causes and prevention of laparoscopic bile duct
injuries. Ann Surg 2003;237:460–469.
Wohl W, Brandt MM, Hammila M, et al. Diagnosis and management of bile leaks after
blunt liver injury. Surgery 2005;138:742–748.
Multidisciplinary
HPB Care
SECTION IV
373
BRIEF HISTORY OF LIVER TRANSPLANTATION
ough orthotopic liver transplantation (LT) rst became a reality in the
early 1960s, outcomes were inadequate to make it the standard of care
for end-stage liver disease until the 1980s. Two primary factors drove the
ultimate success of this procedure: (1) the introduction of calcineurin
inhibitors (cyclosporine) to provide adequate, stable, long-term immu-
nosuppression and (2) the passage of brain death laws that drastically
improved the quality of deceased donor organs. Subsequent improvements
in organ preservation, surgical technique, and intensive care unit manage-
ment have now led to survival approaching 90% at 1 year and 60% to 70% at
10 years. is success has resulted in an unprecedented demand for LT and
has driven the eld of LT in search of more organs. e primary expansion
of donors for LT has come from (1) the use of nonideal (extended criteria)
deceased donors and (2) the use of partial grafts from both deceased and
living donors.
INDICATIONS AND CONTRAINDICATIONS FOR LIVER
TRANSPLANTATION
e primary indications for LT are separated into two disease mecha-
nisms: cholestatic and noncholestatic liver disease. Additionally, LT may
be indicated for certain tumors that meet specic criteria (Table 30.1).
Simultaneous transplantation of the liver with other solid organs has
been well described, including the kidney, pancreas, lung, heart, and
intestine. Unlike kidney and pancreas grafts that are allocated accord-
ing to time on the transplant wait list, liver allografts are allocated solely
based upon severity of illness. e model for end-stage liver disease score
(MELD) was developed to predict the risk of death while awaiting LT. e
MELD score is calculated from three commonly measured laboratory
values (international normalized ratio [INR], serum total bilirubin, and
serum creatinine) and serves to assess synthetic (INR) and excretory (bili-
rubin) function of the liver as well as systemic decompensation (creati-
nine). e MELD score ranges from 6 (low) to 40 (maximum), and patients
are generally not transplanted until their score is greater than 15. MELD
exception points may be granted for the presence of malignant tumor
(hepatocellular carcinoma) or quality of life issues.
Most contraindications to LT are relative but may include active sub-
stance abuse, systemic infection, cancer, HIV infection, poorly managed
psychiatric disorders, lack of social support, and signicant disease of the
cardiopulmonary or neurologic systems. Surveillance for hepatocellu-
lar carcinoma (HCC) is mandatory for all patients with cirrhosis; 70% to
90% of all HCC cases arise in the cirrhotic liver. Scoring systems have been
developed to determine acceptable HCC tumor volume that still permits
Liver and Pancreas
Transplantation
Richard S. Mangus and Jonathan A. Fridell
30
Section IV / Multidisciplinary HPB Care374
LT, the two most common of which are the Milan and the University of
California, San Francisco (UCSF) criteria (Table 30.2). Liver-directed thera-
pies for HCC such as transarterial embolization and radiofrequency abla-
tion are useful and serve to control disease burden while awaiting LT; these
therapies may also be used to downstage HCC volume to meet transplant
criteria.
End-stage liver disease is frequently accompanied by a host of comor-
bidities that may impact the outcome of the transplant. Hepatorenal syn-
drome (HRS) is a condition in which chronic liver disease is associated
with renal insuciency. ough some of the eects of severe HRS may be
reversed with LT, patients do not generally return to completely normal
renal function. Hepatopulmonary syndrome (HPS) results from dierences
in vascular pressures related to the primary liver disease. e vasodila-
tion resulting from liver failure leads to a direct vasodilatory eect in the
lungs, which results in increased blood ow in relation to ventilation and
a ventilation–perfusion mismatch. is is seen clinically as a right-to-left
shunt, and the patient experiences dyspnea. As with HRS, HPS is an impor-
tant marker of disease severity, and prognosis is poor without a timely LT.
Symptoms of HPS improve markedly with LT.
Cholestatic Liver
Disease
Noncholestatic Liver
Disease Other
Primary sclerosing
cholangitis (PSC)
Viral hepatitis Hepatocellular
carcinoma
Primary and secondary
biliary cirrhosis
(PBC)
Alcoholic liver disease (ALD) Cholangiocarcinoma
Biliary atresia Nonalcoholic fatty liver
disease (NAFLD)
Acute liver failure
Cystic brosis Autoimmune hepatitis
Hepatic toxicity from chronic
drug or toxin exposure
Metabolic or genetic
disorders
Common Diseases for Which Liver Transplantation May Be
Indicated
TABLE
30.1
Milan Criteria UCSF Criteria
Number and
size of tumors
Solitary tumor with
maximum diameter of
5cm
Up to three tumor nodules,
each of which is <3cm,
with no vascular
invasion or extrahepatic
metastases
Solitary tumor with
maximum diameter of
6.5cm
Up to three tumor nodules,
with largest nodule
<4.5cm, or a total tumor
diameter <8cm, with
no vascular invasion or
extrahepatic metastases
Criteria for Liver Transplantation in Patients with Hepatocellular
Carcinoma
TABLE
30.2
Chapter 30 / Liver and Pancreas Transplantation 375
PROCEDURE/TECHNIQUE
Organ Procurement from Deceased Donors
e organ procurement operation from a deceased donor is standard-
ized with little variation among surgeons. Safe preservation of the organs
is dependent upon two primary principles: (1) rapid organ exsanguina-
tion and vascular ushing with an appropriate preservation solution and
(2) rapid organ cooling. After the organs have been prepared in the donor,
an aortic cannula is placed that is used to ush the arterial system. Some
surgeons choose to place a second cannula in the portal vein (through the
inferior mesenteric vein) to ush the portomesenteric system. e abdom-
inal aorta is clamped superior to the celiac trunk and also near the iliac
bifurcation to isolate the abdominal organs. e outow for the blood and
preservation solution is generally through the suprahepatic vena cava at
its junction with the right atrium. As the clamps are placed and the pres-
ervation solution is infused, iced normal saline is placed throughout the
abdominal cavity to topically cool the organs. e heart arrests during this
process, and the organs are then removed. For living donor partial liver
procurement, the liver resection is performed in the donor with dissection
completed while vascular inow and outow remains intact. Clamps are
applied simultaneously, and the donor graft is removed, followed by rapid
ushing and cooling (Fig. 30.1A and B). Donation after cardiac death (DCD)
is currently used in 4% of deceased donors and requires complete cessation
of cardiopulmonary function prior to organ procurement. is necessar-
ily results in several minutes of graft warm ischemia time, which results
in inferior outcomes. In all cases, once procured, the liver allograft must
be transplanted and reperfused within 12 hours, after which there is an
increased risk of complications.
Liver Transplant Operation
ere are three components to the liver transplant operation: (1) prepara-
tion of the transplant organ, (2) recipient hepatectomy, and (3) implanta-
tion of the graft. Preparation of the graft involves removal of residual tissue
from the donor operation including residual diaphragm and pericardium
around the vena cava and hepatic veins. e gallbladder is always removed
from the donor liver, and the cystic duct is ligated. Accessory hepatic arter-
ies are carefully dissected and preserved. An accessory right hepatic artery
requires reconstruction prior to transplantation. Frequently, an accessory
left hepatic artery cannot be safely reconstructed, because of small size,
and is dissected and preserved in situ.
e recipient hepatectomy is performed in one of two ways: (1) con-
ventional (standard bicaval) or (2) the piggyback or “cava-preserving” tech-
nique (Fig. 30.2A and B). Both approaches to the hepatectomy require initial
takedown of the falciform and gastrohepatic ligaments, followed by dissec-
tion of the hilum of the liver with transaction of the hepatic artery, common
bile duct, and portal vein. e conventional approach then proceeds with
clamping of the vena cava above and below the liver with transaction of
the vena cava between the clamps and removal of the liver. is technique
necessarily requires complete clamping of the vena cava for a prolonged
period of time. e piggyback technique varies from this approach with
no clamping of the vena cava required. For the piggyback hepatectomy,
the liver is carefully retracted away from the vena cava with perforating
branches between the vena cava and the liver individually ligated and tran-
sected. Eventually, the liver remains attached only by the hepatic veins. e
veins are clamped and transected, and the liver is removed. e piggyback
technique is technically more dicult than the conventional approach, but
Section IV / Multidisciplinary HPB Care376
FIGURE 30.1 A. Living donor left lateral segment graft for a pediatric recipient. B. Living
donor right lobe graft for an adult recipient.
Chapter 30 / Liver and Pancreas Transplantation 377
FIGURE 30.2 A. Conventional or standard bicaval anastomosis of the vena cava.
B. Piggyback or “cava-preserving” technique for LT.
Section IV / Multidisciplinary HPB Care378
the recipient tends to remain more hemodynamically stable as the preload
to the heart from the lower body is never interrupted. Some surgeons who
use the piggyback approach construct a temporary portacaval shunt to
decompress the portomesenteric system until the time of liver allograft
reperfusion. e piggyback approach may be the preferred method in
high-risk patients such as the elderly, those with poor physiologic reserve,
or patients who are hemodynamically unstable. e piggyback technique
tends to preserve hemodynamic and physiologic stability throughout the
transplant, which may then be associated with less perioperative morbidity
and mortality.
Finally, the transplant is performed. For the conventional approach,
the vena cava must be reanastomosed both above and below the liver. For
the piggyback technique, the liver outow is through the clamped hepatic
veins so that a single anastomosis is required. is reduction from two to
one vena cava anastomosis can decrease critical warm ischemia time by as
much as 5 to 10 minutes. Next, the portal vein and hepatic artery are anas-
tomosed. Finally, the common bile duct can be anastomosed, after the liver
has been fully reperfused, either to the recipient common bile duct or to a
Roux-en-Y limb of the small intestine. At our center, 90% of our transplants
employ a primary duct-to-duct reconstruction, and we never use a T tube.
In countries with limited access to deceased donors, partial liver
allografts from living donors may be the only option available for patients in
need of transplantation. Also, splitting of a whole deceased donor liver can
result in two viable grafts, though each split portion carries an increased
risk of complications when compared to a whole organ allograft. e living
donor partial liver transplant requires use of the piggyback hepatectomy
because there is no vena cava available from the living donor. erefore,
the donor hepatic vein is anastomosed to the recipient hepatic veins, with
portal and arterial inow constructed directly to the native portal vein and
hepatic artery (Fig. 30.3). e bile duct is transected close to the liver graft
and is generally reconstructed with a Roux-en-Y limb of jejunum.
COMPLICATIONS
Immediate posttransplant complications may result from technical issues
related to the transplant procedure, poor function of the graft, or recipient
health issues. e most critical early posttransplant complication is throm-
bosis of the hepatic artery or the portal vein. rombosis of the hepatic vein
anastomosis is very uncommon. e liver requires both hepatic artery and
portal vein inow for survival, and thrombosis of either anastomosis places
the graft at imminent risk of failure. Doppler ultrasound is utilized post-LT
to assure that vascular ow remains adequate. A loss of ow in either vessel
generally necessitates emergent return to the operating room to reestab-
lish ow. Posttransplant bleeding in the rst 24 to 48 hours is not uncom-
mon and requires reexploration to identify and control the source. Primary
nonfunction (PNF) is a denition of exclusion in which there is graft failure
within 7 days of the transplant with no other identiable cause. PNF occurs
in 1% to 5% of liver transplants and may be related to prolonged ischemia
time, old donor age, and severe steatosis. Small for size graft is a syndrome
seen almost exclusively in partial LT. e small size of the transplant graft in
relation to the recipient blood ow results in persistent portal hypertension
and liver congestion as the portomesenteric ow is too great for the partial
liver graft segment. is syndrome is a major cause of early graft loss in liv-
ing donor transplantation.
Biliary complications may be seen within the rst week posttrans-
plant but may also occur several weeks or months later. ere are three
Chapter 30 / Liver and Pancreas Transplantation 379
primary complications of the bile duct: (1) biliary leak, (2) anastomotic
stricture, and (3) intrahepatic strictures. Biliary leak is encountered in the
perioperative period and may be technical in nature or may result from bile
duct necrosis. Biliary complications are particularly problematic in living
donor LT and are a major cause of graft loss and patient death in this popu-
lation. Most anastomotic strictures, and many anastomotic leaks, can be
treated nonoperatively with endoscopic retrograde cholangiopancreatog-
raphy or percutaneous transhepatic cholangiography. rough these tech-
niques, stents can be placed across the anastomosis to facilitate drainage,
and these can be increased in size over time to dilate the duct. Intrahepatic
strictures appear as multiple diuse strictures within a region of the liver or
across the entire liver. Diuse intrahepatic structuring points to a systemic
problem usually related to arterial blood ow. Liver allografts procured
from deceased donors using a DCD protocol are at increased risk of diuse
intrahepatic strictures. Patients who develop diuse intrahepatic biliary
strictures have a high rate of graft loss and frequently require retransplan-
tation within 1 year.
An important impediment to success in the eld of LT is the side
eects of immunosuppressive drugs. ese powerful agents, though eec-
tive at preventing rejection, continue to have major side eects that impact
on long-term patient morbidity and mortality. Many centers now use
FIGURE 30.3 Implantation of the right lobe graft into an adult.
Section IV / Multidisciplinary HPB Care380
antibody-based immunosuppression induction at the time of transplant,
followed by one, two, or three drug maintenance regimens. Rejection of the
liver allograft is less common than that seen for other solid organs. In fact,
the liver appears to lessen the rejection risk of other organs when they are
transplanted simultaneously. e reason for this nding is unclear. Because
the liver transplant procedure itself is clean, intraabdominal infections
post-LT are rare. Bacterial wound infections, however, are common for a
variety of reasons. e liver transplant incision is quite large, and patients
with liver failure are malnourished and have poor healing capacity. Many
liver transplant recipients receive perioperative steroids, which impacts
wound healing directly. Finally, clinical comorbidities such as diabetes and
obesity contribute to poor wound healing and infection. e most common
opportunistic viral infection in the liver transplant patient is cytomegalovi-
rus (CMV) infection with a 1-year risk of 5% to 20%. Anti-CMV prophylaxis
with valganciclovir and minimization of immune suppression lower the
rate of this infection. Fungal infections can occur in up to 20% of patients
and are most commonly seen in the mouth, esophagus, and urine. ese
infections almost always result from Candida species and respond to stan-
dard treatments.
Nearly all post-LT immunosuppression protocols utilize calcineurin
inhibitors as the primary immunosuppressant drug. Use of these agents
has resulted in nephrotoxicity being one of the primary long-term major
complications associated with solid organ transplantation. Finally, the
immune system plays a critical role in neoplasm surveillance in the human
body. e chronic immune suppression required by all transplant patients
places them at increased risk for the development of cancer, and this is well
documented. e cancers found in transplant patients tend to mirror those
seen in the general population, but with increased frequency. erefore, the
cancer most commonly seen in transplant patients is skin cancer (squa-
mous and basal cell). Patients with HCC at the time of transplant have a
risk of HCC recurrence posttransplant, but their survival is similar to that
for non-HCC patients if they are within the Milan criteria at the time of
transplant. Posttransplant lymphoproliferative disorder (PTLD) is well
described and appears to have increasing risk with increasing levels of
immune suppression.
PANCREAS TRANSPLANTATION
Introduction
Pancreas transplantation can restore normal insulin secretion and eugly-
cemia in insulinopenic diabetic recipients. Since the rst pancreas trans-
plant performed by Lillehei and Kelly at the University of Minnesota in
1966, pancreas transplantation has evolved to the point where there are
more than 1,500 procedures performed annually in the United States and it
is routinely oered at most abdominal organ transplant centers. Outcomes
have improved steadily over the decades, owing to improvements in organ
preservation, surgical technique, postoperative care, and immunosuppres-
sion. Nonetheless, the need for a major operation and the requirement
for lifelong immunosuppression have limited the application of pancreas
transplantation to very select diabetic populations.
INDICATIONS
e majority of pancreas transplants are performed in association with
another organ transplant in recipients with type 1 diabetes mellitus. e
other organ transplanted is almost always a kidney transplant for end-stage