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locoregional lymphadenopathy, and hepatectomy . Although long-term survival after
curative-intent surgery for perihilar cholangiocarcinoma has dramatically increased
to a 5-year survival rate of more than 30 % along with the evolution of surgical
management , the mortality rates and complication rates after this challenging operation remain high, even in high-volume centers (mortality rate is usually under
10 %, but the morbidity rate is up to 70 %) [ 1 ].
In this challenging background, surgical management for perihilar cholangiocarcinoma is associated with many controversial ‘diffi cult decisions’, including those
regarding preoperative biliary drainage; preoperative portal venous embolization ;
and the extent of surgical resection , such as vascular resection, lymphadenectomy,
and hepatectomy [ 2 , 3 ]. Achieving a bile duct margin-negative resection, however,
is one of the most important issues to consider in the surgical approach for perihilar
cholangiocarcinoma. Meticulous evaluation of the ductal spread of the tumor is
critical.
This chapter addresses the preoperative and intraoperative assessment of the
ductal spread of hilar cholangiocarcinoma to achieve a negative margin (R0) in
curative-intent aggressive surgery .
Search Strategy
A literature search of English - language publications from 2009 to 2014 (within the
last 5 years) was used to identify published data on assessment of the ductal margin
in surgery for perihilar cholangiocarcinoma using the PICO outline (Table 31.1 ).
We searched the PubMed, Embase, Science Citation Index/Social sciences Citation
Index, and Cochrane Evidence Based Medicine databases. The search terms used
were “perihilar cholangiocarcinoma” or “hilar cholangiocarcinoma” AND “surgical
treatment” and “ diagnosis ”. Case reports, and studies focusing only on the surgical
technique or diagnostic approach, or dealing only with selected cases or specifi c
technique were excluded. Finally, 51 cohort studies and 34 review articles were
included in our analysis. No randomized control trials were identifi ed. The data
were classifi ed using the GRADE (Grading of Recommendations, Assessment,
Development, and Evaluation) system.
Table 31.1 PICO table for assessment of the ductal margin in curative-intent surgery for perihilar
cholangiocarcinoma
P (Patients) I (Intervention) C (Comparator group)
O (Outcomes
measured)
Patients undergoing
curative- intent surgery for
perihilar cholangiocarcinoma
Curative-intent
resection
Preoperative assessment
of the tumor extent by
cholangiography versus
MDCT/MRC
R0 resection rate,
5-year patient
survival
Abbreviations: MDCT multidetector-row computed tomography , MRC magnetic resonance cholangiography
N. Akamatsu et al.
351
Results
Importance of a Negative Resection Margin for Prognosis After Curative-Intent Surgery for Perihilar Cholangiocarcinoma
In most of the published studies [ 4 – 12 ], a negative resection margin was considered
the most important determinant of a better prognosis after curative-intent resection
for perihilar cholangiocarcinoma . Median overall survival time was signifi cantly
longer after a margin-negative resection than after a margin-positive resection:
24–58 months versus 12–28 months. Accordingly, surgeons have attempted to
achieve a negative bile duct margin using various aggressive approaches.
Achieving a Negative Bile Duct Margin: Hepatectomy Versus Bile Duct Resection
Curative-intent surgery for perihilar cholangiocarcinoma has evolved from an extrahepatic bile duct resection to an aggressive approach, including meticulous and
challenging hepatectomies. The benchmark study by Tsao and colleagues [ 13 ],
comparing the Japanese (Nagoya) experience with the USA (Lahey) experience,
with a liver resection rate of 89 % vs 16 %, a caudate lobectomy rate of 89 % vs
8 %, and a resectability rate of 79 % vs 25 %, respectively, promoted an aggressive
approach for hilar cholangiocarcinoma worldwide. While the mortality rate was
higher in Nagoya (8 % vs 4 %), the margin-negative resection and 5-year survival
were signifi cantly higher in the Nagoya group (79 % vs 28 %, and 16 % vs 7 %,
respectively). Recent convincing evidence indicates that aggressive surgical resection with hepatectomy signifi cantly improves patient survival [ 4 – 6 , 10 , 11 , 14 ];
median overall survival time was 40–47 months in patients with hilar cholangiocarcinoma who underwent liver resection, while it was 15–30 months in those that
underwent only bile duct resection. Type of hepatectomy also appears to be associated with margin-negative resection rates and long-term patient survival [ 15 , 16 ].
Impact of Caudate Lobectomy in Hepatectomy for Hilar Cholangiocarcinoma
Caudate lobectomy in hepatectomy for perihilar cholangiocarcinoma remains controversial [ 17 , 18 ]. Routine en bloc resection of the caudate lobe was initially advo-
cated by Japanese surgeons based on an anatomic viewpoint [ 19 ]. Perihilar
cholangiocarcinoma frequently invades the caudate lobe bile duct and the caudate
lobe appears to be a common site for locoregional recurrence after curative-intent
31 The Assessment of Ductal Margin in Curative-Intent Surgery for Perihilar…
352
resection for perihilar cholangiocarcinoma. Further, extended hepatectomy, including caudate lobectomy, increases margin-negative resections. Routine caudate
lobectomy for perihilar cholangiocarcinoma is currently accepted in Western institutions [ 7 , 20 , 21 ]. Whether caudate lobectomy improves long-term patient survival ,
however, is controversial, with some reports [ 13 , 17 , 18 ] of a positive impact on
survival and others [ 7 , 10 , 21 ] demonstrating no correlation with patient survival.
Preoperative Assessment of Perihilar Cholangiocarcinoma
Preoperative radiologic evaluation is mandatory for accurate assessment of the
tumor extent , which is integral to planning the surgical procedure. Preoperative
evaluation of perihilar cholangiocarcinoma in terms of radical resection comprises
a multidisciplinary approach with ultrasonography, helical- computed tomography ,
magnetic resonance imaging (MRI) including MR cholangiography (MRC), direct
cholangiography via endoscopic retrograde cholangiography or percutaneous transhepatic biliary drainage, intraductal ultrasonography (IDUS), peroral cholangioscopy, and biopsy [ 22 ].
Among these, dynamic multidetector-row computed tomography (MDCT) is
now widely used for preoperative evaluation and staging of hilar cholangiocarcinoma, as it provides not only a qualitative diagnosis and indicates the extent of the
tumor, but it also shows the relationship between adjacent tissues, such as the
hepatic artery, portal vein, and liver parenchyma.
In enhanced MDCT, bile duct cancer is often revealed as a focal thickening of the
ductal wall with various enhancement patterns. The accuracy of the differential
diagnosis of a malignant lesion from benign stenosis is reported to be over 90 %,
with satisfactory accuracy in evaluating major vessel involvement and liver parenchyma invasion. Yet, lymph node metastasis remains diffi cult to diagnose preoperatively, even with the recent increased resolution of MDCT [ 23 , 24 ]. Some authors
report that MDCT is effective for evaluating longitudinal spread along the bile duct,
demonstrating that the effi cacy is equivalent to that of evaluation using MRC or
direct cholangiography [ 25 , 26 ]. Additional important information obtained from
MDCT and its three-dimensional (3D) and multiplanar reconstruction for surgeons
is the precise arterial/portal/venous anatomy around the hepatic hilum and hepatoduodenal ligament in relation to the tumor. MDCT and its 3D images and multiplanar
reconstructions are important for preoperative planning and for navigation during
the operation [ 27 ].
MRI with concurrent MRC provides 3D reconstruction of the biliary tree, and
the diagnostic accuracy for evaluating perihilar cholangiocarcinoma is comparable
to that of invasive cholangiography via endoscopic retrograde cholangiography or
percutaneous transhepatic biliary drainage [ 28 , 29 ]. MRI also facilitates evaluation
of vertical tumor invasion, similar to MDCT. To exclude artifacts of biliary instrumentation and obtain precise images of ductal wall thickening and luminal stenosis/
N. Akamatsu et al.
353
dilatation, both MDCT and MRC are strongly recommended before decompressing
the biliary tree.
Despite the evolution of MDCT and MRC described above, direct cholangiography remains the gold standard for the preoperative evaluation of ductal spread.
While there are some drawbacks with the endoscopic or transhepatic approach,
these procedures enable bile duct biopsy, IDUS, and choledochoscopy, all of which
may enhance preoperative diagnostic accuracy.
Assessment of the Bile Duct Margin and Operative Outcome
To date, there has been no randomized controlled trial or comparative study regarding assessment of the extent of perihilar cholangiocarcinoma. Thus, we collected
recent retrospective cohort studies of curative-intent surgery for perihilar cholangiocarcinoma from high-volume centers based on the following inclusion criteria; (1)
published within the last 5 years, (2) included over 100 cases, (3) provided the
preoperative assessment for ductal spread of the tumor, and (4) provided the R0 rate
and 5-year survival rate. Finally, 12 studies comprising 2,343 cases of perihilar
cholangiocarcinoma were enrolled in the present review (Table 31.2 ) [ 4 – 6 , 10 – 12 ,
16 , 17 , 30 – 33 ].
Seven centers used cholangiography as the primary modality for preoperative
assessment of the bile duct margin, while fi ve centers used MRC or MDCT as the
primary modality for assessing the ductal spread of perihilar cholangiocaricinoma.
Intraoperative assessment with frozen sections was routinely performed in four centers. The simultaneous liver resection rate was uniformly high (median 97 %, range
75–100 %), with a median R0 rate of 75 % (range 63–89 %), and a median 5-year
survival rate of 33 % (range 29–38 %). These homogeneous results represent the
standardization of the surgical approach against perihilar cholangiocarcinoma
within the last two decades.
When the cases were divided according to preoperative assessment of the bile
duct margin, the R0 rate was 75 % (878/1169) with cholangiography and 77 %
(884/1147) with MDCT or MRC, a difference that was not signifi cant. Similarly,
collection of intraoperative frozen sections did not signifi cantly affect the R0 rate;
with frozen sections, 69 % (554/799), and without frozen sections, 78 % (1208/1544).
Recommendations
In the absence of effective treatment other than surgical resection , curative-intent
surgery should be planned for patients with perihilar cholangiocarcinoma. With the
evolution of the knowledge of perihilar anatomy and surgical techniques, including
perioperative management , extended hepatectomy with complete resection of the
31 The Assessment of Ductal Margin in Curative-Intent Surgery for Perihilar…
354
Table 31.2 Studies with a large cohort reporting the results of curative-intent surgery for perihilar Cholangiocarcinoma
Author Year Period Patients, n
Preoperative
assessment of
the ductal margin
Intraoperative
frozen section
Liver
resection, % R0, %
5-year
survival
rate, %
Study type
( quality of
evidence)
Chen et al. [
30 ] Tongji, China 2009 2000–2007 138 Cholangiography No 100 89 30 Retrospective
cohort (low)
Lee et al. [
5 ] Seoul, Korea 2010 2001–2008 302 Cholangiography Yes 89 71 33 Retrospective
cohort (low)
Shimizu et al.
[
16 ]
Chiba Japan 2010 1984–2008 224 Cholangiography No 100 74 29 Retrospective
cohort (low)
Hirano et al.
[
31 ]
Hokkaido,
Japan
2010 2001–2008 146 Cholangiography No 94 87 35 Retrospective
cohort (low)
Unno et al. [
32 ] Tohoku, Japan 2010 2001–2008 125 MDCT Yes 100 63 35 Retrospective
cohort (low)
Li et al. [
12 ] Tianjin, China 2011 1990–2009 215 Cholangiography Yes 95 66 30 Retrospective
cohort (low)
Cho et al. [
11 ] Seoul, Korea 2012 2000–2009 105 MDCT No 75 71 34 Retrospective
cohort (low)
Matsuo et al. [
4 ] New York,
USA
2012 1991–2008 157 MRC or MDCT Yes 82 76 32 Retrospective
cohort (low)
Cheng et al. [
17 ] Shanghai,
China
2012 2001–2010 171 MRC or MDCT No 100 78 33 Retrospective
cohort (low)
Song et al. [
10 ] Seoul, Korea 2012 1995–2010 230 MRC or MDCT No 77 77 33 Retrospective
cohort (low)
Nagino et al. [
6 ] Nagoya, Japan 2013 2001–2010 386 Cholangiography No 99 78 38 Retrospective
cohort (low)
Furusawa et al.
[
33 ]
Nagano, Japan 2013 1990–2012 144 Cholangiography No 99 74 33 Retrospective
cohort (low)
Abbreviations: MDCT multidetector-row computed tomography , MRC magnetic resonance cholangiography
N. Akamatsu et al.
355
caudate lobe is recommended in the absence of clinical restrictions, such as liver
dysfunction or apparently insuffi cient remnant liver. Enhanced MDCT with 3D and
multiplanar reconstruction is becoming mandatory both for precise preoperative
evaluation of the tumor extent and safe and curative surgical resection of perihilar
cholangiocarcinoma. In contrast, direct cholangiography remains the gold standard
for preoperative evaluation of the bile duct margin, while the diagnostic accuracy of
MDCT or MRC seems comparable to that of direct cholangiography. Given the
absence of high quality evidence, the modality for preoperative evaluation of the
bile duct margin and surgical planning can be selected based on the surgeon’s
preference.
A Personal View of the Data
Considering that histopathologic examinations have low sensitivity, non-diagnostic
cytology or biopsy results may not rule out cholangiocarcinoma in the presence of
appropriate radiologic fi ndings. Further, due to the possibility of procedure-related
complications, we do not recommend routine direct cholangiography and biopsy for
bile duct margin evaluation in perihilar cholangiocarcinoma. MDCT with 3D and
multiplanar reconstruction or MRC can replace these invasive modalities to evaluate tumor extent . In patients with jaundice requiring biliary decompression, direct
cholangiography via an inserted tube or IDUS and biopsy at the time of tube insertion facilitates the diagnosis . The benefi t of additional resection based on a positive
frozen section is controversial [ 34 , 35 ], and we believe that preoperative surgical
planning for an extended resection to achieve a negative margin to the extent possible is much more important. Additional resection of the bile duct may be technically limited. The best modality to gain the maximum diagnostic accuracy, achieve
a high R0 resection rate, and improve patient survival remains to be investigated in
future prospective studies.
Recommendations
• For patients with perihilar cholangiocarcinoma without distant metastasis, we
recommend an extended hepatectomy with complete resection of the caudate
lobe in curative-intent surgery .
• Enhanced MDCT with 3D and multiplanar reconstruction is mandatory for both
precise preoperative evaluation of tumor extent and safe and curative surgical
resection , while the gold standard for evaluation of the bile duct margin can be
either cholangiography or MDCT/MRC, depending on the surgeon’s preference.
• We recommend that the initial resection be extended as far as possible to achieve
a negative margin, rather than performing additional resection based on a posi-
tive margin determined from routine intraoperative frozen sections.
31 The Assessment of Ductal Margin in Curative-Intent Surgery for Perihilar…
356
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31 The Assessment of Ductal Margin in Curative-Intent Surgery for Perihilar…
359© Springer International Publishing Switzerland 2016
J.M. Millis, J.B. Matthews (eds.), Diffi cult Decisions in Hepatobiliary
and Pancreatic Surgery, Diffi cult Decisions in Surgery: An Evidence-Based
Approach, DOI 10.1007/978-3-319-27365-5_32
Chapter 32
Management of Early Post-transplant Portal
Vein Thrombosis: Results of Interventional
Techniques Versus Surgical
Jonathan M. Lorenz and Mikin V. Patel
Abstract Portal vein thrombosis (PVT) is an uncommon complication of liver
transplantation, occurring in less than 4 % of patients. PVT can be immediately lifethreatening when it presents with signs and symptoms during the acute stage in the
general population or early after liver transplantation. In transplant recipients, most
cases present early, which results in a greater risk of loss of the liver graft. Despite
substantial morbidity associated with PVT in liver transplant recipients, scant published literature exists to guide clinical management. Limited, small retrospective
series address PVT in the general population, but the surgical or endovascular management of PVT in transplant recipients is rarely addressed. Anticoagulation is standard therapy in patients with native livers, but in the setting of early post- transplant
PVT, this treatment as a sole option is usually insuffi cient given the tendency toward
clinical progression and graft loss. No consensus exists regarding the appropriate
application of surgical or endovascular revascularization, but endovascular therapies may avoid the risks of re-do operations in transplant patients.
Keywords Portal thrombosis • Liver transplant • Thrombolysis • Thrombectomy
Introduction
Portal vein thrombosis (PVT) with or without involvement of the mesenteric vein
(portal-mesenteric venous thrombosis: PMVT) is an uncommon complication of
liver transplant ation [ 1 – 4 ] in the absence of pre-transplant thrombosis or other portal venous pathology. In patients with native livers, up to 75 % of cases of PVT
result from an identifi able cause – most commonly hypovolemic and hypercoagulable states, and abdominal infection, infl ammation or surgery [ 5 ]. Liver transplant
J. M. Lorenz (*) • M. V. Patel
Department of Radiology , University of Chicago Medical Center ,
5841 S. Maryland Ave. MC2026 , Chicago , IL 60037 , USA
e-mail:
jlorenz@radiology.bsd.uchicago.edu
360
recipients often have a combination of these factors in addition to an increased risk
of mechanical obstruction of the portal vein.
PVT can be immediately life-threatening when it presents with signs and symptoms during the acute stage (<7 days) in the general population or early (<30 days)
after liver transplant ation . Cases that present in the second to fourth week after
thrombosis are considered subacute. Most transplant-related cases occur in this
early period [ 3 , 6 ], which predisposes these patients to a high risk of graft loss.
Acute presentation increases the risk of progression to PMVT, which carries a
higher risk of bowel infarction, peritonitis, complications of portal hypertension,
and death. The need for emergent surgery in such cases adds additional morbidity .
Persistence of untreated PVT to the chronic stage may result in portal hypertension
and limited options for surgical shunt placement or retransplantation.
Evidence-based evaluation of the risks and outcomes of both surgical and endovascular techniques to manage PVT is made diffi cult by its low incidence, which
has heretofore prevented the publication of prospective comparative trials and limited the publication of large, retrospective series. Surgical or endovascular revascularization may offer a durable solution, but no expert consensus exists regarding the
appropriate application of these techniques. Endovascular techniques for PVT
remain in the feasibility and pilot stages, but these therapies promise to avoid the
risks of re-do operations in select post-surgical patients. Some guidance regarding
technical success, clinical success, and complication rates can be gleaned from a
review of the few published cases related to transplant patients coupled with published retrospective studies evaluating relevant therapies that have been applied to
patients with native livers complicated by PVT.
Search Strategy
A literature search of English language publications from 1980 to 2014 was used to
identify published series on the application of surgical or endovascular revascularization for the treatment of PVT and PMVT in liver transplant recipients as well as
patients with native livers. The decision to include PVT in non-transplant patients
resulted from an exceedingly low number of published cases describing endovascular therapies that are applicable to transplant patients. The PICO outline was used
(Table 32.1 ). Databases searched were PubMed and Embase. Terms used in the
Table 32.1 PICO table for the management of PVT and PVMT
P (Patients) I (Intervention) C (Comparator group) O (Outcomes measured)
Patients
with PVT
or PMVT
Endovascular
revascularization
Surgical
revascularization
Restoration of PV patency, resolution
of clinical signs and symptoms,
recurrence, complications
J.M. Lorenz and M.V. Patel