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Anesthesia for laparoscopic liver surgery 179
Box 11.3 ASA advisory statements for patient positioning
Preoperative history and physical assessment
When judged appropriate, it is helpful to ascertain that patients can comfortably tolerate the anticipated operative position
Specific positioning strategies for the upper extremities
• Arm abduction in supine patients should be limited to 90°
• Supine patient with arm on an armboard
♦
The upper extremity should be positioned to decrease pressure on the postcondylar groove of the humerus (ulnar groove)
♦
Either supination or the neutral forearm position facilitates this action
• Supine patient with arms tucked at side
♦
The forearm should be in a neutral position
♦
Flexion of the elbow may increase the risk of ulnar neuropathy, but there is no consensus on an acceptable degree of flexion
during the perioperative period
• Prolonged pressure on the radial nerve in the spiral groove of the humerus should be avoided
• Extension of the elbow beyond the range that is comfortable during the preoperative assessment may stretch the median nerve
• Periodic perioperative assessments may ensure maintenance of the desired position
Specific positioning strategies for the lower extremities
• Stretching of the hamstring muscle group
♦
Positions that stretch the hamstring muscle group beyond the range that is comfortable during the preoperative assessment
may stretch the sciatic nerve
• Limiting hip flexion
♦
Because the sciatic nerve or its branches cross both the hip and the knee joints, extension and flexion of these joints,
respectively, should be considered when determining the degree of hip flexion
• Neither extension nor flexion of the hip increases the risk of femoral neuropathy
• Prolonged pressure on the peroneal nerve at the fibular head should be avoided
Protective padding
• Padded armboards may decrease the risk of upper extremity neuropathy
• The use of chest rolls in the laterally positioned patient may decrease the risk of upper extremity neuropathy
• Padding at the elbow may decrease the risk of upper extremity neuropathy
• The use of specific padding to prevent pressure of a hard surface against the peroneal nerve at the fibular head may decrease the
risk of peroneal neuropathy
• The inappropriate use of padding (e.g. padding too tight) may increase the risk of perioperative neuropathy
Equipment
• The use of properly functioning automated blood pressure cuffs on the arm (i.e. placed above the antecubital fossa) does not
change the risk of upper extremity neuropathy
• The use of shoulder braces in a steep head-down position may increase the risk of perioperative neuropathies
Postoperative assessment
• A simple postoperative assessment of extremity nerve function may lead to early recognition of peripheral neuropathies
Documentation
• Documentation of specific perioperative positioning actions may be useful for continuous improvement processes and may result
in improvements by (i) helping practitioners focus attention on relevant aspects of patient positioning, and (ii) providing information on positioning strategies that eventually leads to improvements in patient care
180 Chapter 11
KEY POINTS
• Liver pathophysiology is dependent on underlying liver disease and tumor histology. Resulting changes in coagulation and
metabolism have to be considered.
• A thorough preoperative patient assessment is important, taking specific aspects of laparoscopy and liver surgery into account.
• Establishment of pneumoperitoneum and patient positioning have critical effects on ventilation, hemodynamics, and end-organ
perfusion, including the liver.
• Establishment and maintenance of anesthesia need to be accomplished with low IVC pressures to minimize hepatic ve nous
bleeding.
• Complications specific to laparoscopic liver surgery such as gas embolism require prevention and management strategies.
• Successful advanced laparoscopic liver surgery can only be accomplished if surgeon and anesthesiologist establish a relationship
of excellent communication and trust.
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Videos 1–20 will be of interest to readers of this chapter.
Visit the companion website at:
of hospital-wide pain management standards: is patient
safety compromised by treatment based solely on num erical
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www.wiley.com\go\conrad\liver-pancreas-biliary-laparoscopic-surgery
CHAPTER 12
Oncological management of primary liver
cancer in the era of minimal access surgery
Jennifer Chan
Department of Medical Oncology, Dana-Farber Cancer Institute, Ha rvard Medical School, Boston, USA
EDITOR COMMENT
In this chapter, an expert view on the general oncological management of primary liver cancer is given. Primary liver cancers, which
include hepatocellular carcinoma and biliary tract cancers, represent a major global health problem. For patients with early-stage disease,
surgical resection represents an optimal curative treatment modality with a growing role for the minimally invasive approach; ablative
therapy can also be considered for small hepatocellular carcinomas. The overall prognosis for primary liver cancers remains poor because
of the presence of advanced-stage disease for most patients at the time of diagnosis, underlying liver dysfunction that limits treatment
options and survival, and only modest benefits of systemic therapy. Despite these problems, advances in surgical, radiation, and hepatic
artery-based techniques plus the development of molecularly targeted agents have led to improvements in patient outcome. The reader
will learn how a dedicated multidisciplinary approach is critical for optimizing patient outcomes.
Keywords: chemotherapy, cholangiocarcinoma, hepatic artery embolization, hepatocellular carcinoma, laparoscopic resection of
primary liver cancer, radiation, radiofrequency ablation, sorafenib
12.1 Introduction
As the second most common cause of cancer-related
mortality worldwide, primary liver cancers, which include
hepatocellular carcinoma and biliary tract cancers, represent a major global health problem [1]. Liver cancers are
most prevalent in less developed regions of the world but
also remain a challenge in developed nations. In the
United States, the incidence and mortality rates are
increasing for liver cancers, in contrast to stable or declining trends for most other cancers [2]. The prognosis for
patients with primary liver cancers remains poor because
of the presence of advanced, unresectable disease for most
patients at the time of diagnosis, underlying liver disease
that limits treatment options and survival, and only modest benefits of systemic therapy. Despite these problems,
advances in surgical, radiation, and interventional radiology techniques plus the development of molecularly targeted agents have led to improvements in patient
Laparoscopic Liver, Pancreas, and Biliary Surgery: Textbook and Illustrated Video Atlas, First Edition.
Edited by Claudius Conrad and Brice Gayet.
© 2017 John Wiley & Sons, Ltd. Published 2017 by John Wiley & Sons, Ltd.
outcome. A multidisciplinary approach is critical for optimizing outcome of patients with primary liver cancers.
12.2 Hepatocellular carcinoma
Several factors pose challenges to the management of
patients with hepatocellular carcinoma (HCC). First, most
patients present with advanced disease or vascular invasion that limits curative treatment options, including
surgery, liver transplantation, or ablative therapy. Second, HCC arises in the setting of chronic liver disease and
cirrhosis in over 80% of patients [3,4]. Underlying liver
disease can adversely affect overall survival, limit surgical
options, and influence tolerance to anticancer therapy by
affecting drug metabolism and increasing risk of adverse
events. Finally, HCC has a chemoresistant phenotype
with a complex and heterogeneous biology that has posed
challenges to the efficacy of systemic therapy.
185
186 Chapter 12
Figure 12.1 Staging, management recommendations, and prognosis of patients with HCC according to the Barcelona Clinic Liver
Classification (BCLC). Source: Llovet [7]. Reproduced with permission of Elsevier.
Various staging schemes exist for stratifying patient
outcome,each of which has its advantagesand limitations.
Whereas the TNM system of the American Joint Committee on Cancer(AJCC) incorporates pathologicalfeatures of
disease [5,6], others, such as the Barcelona Clinic Liver
Cancer (BCLC) [7], Cancer of the Liver Italian Program
(CLIP)[8], Okuda [9], JapanIntegratedStagingScore [10],
algorithm based on stage (Figure 12.1). Although treatment algorithms such as the one proposed by the BCLC
are helpful for understanding options that exist for particular groups patients, it is important to recognize that
indications and treatment are evolving and that individualizing treatment decisions within the context of multi-
disciplinary evaluation remains critical.
and Chinese University Prognostic Index (CUPI) [11] systems, take into account measures of underlying liver
function in addition to an assessment of extent of disease.
Although multiple staging and scoring systemsexist, there
is not one universally accepted classification. Furthermore, because of the geographic variation in risk factors
for development of HCC, one staging system may perform
better than others in certain regions.
The BCLC staging system, which includes factors
related to tumor burden, liver function, and performance
status, also incorporates a recommended treatment
12.2.1 Management of early-stage HCC
For patients with early-stage HCC, potentially curative
treatment options exist, including surgical resection, liver
transplantation, or ablative therapies. For patients without cirrhosis, surgical resection is the preferred management [12,13]; five-year survival following resection in
these patients approaches 50% [14–16]. The majority of
patients (>80%), however, develop HCC within the
context of cirrhosis. Resection of HCC in patients with
cirrhosis requires cautious selection, taking into account
Oncological management of primary liver cancer 187
tumor-related features (number and size of lesions, vascular invasion, presence of extrahepatic disease) and
patient-dependent factors (liver function, performance
status, medical comorbidities) [15,17–20]. Optimal outcomes following resection of HCC have been observed in
patients with preserved liver function without evidence
of portal hypertension, adequate hepatic reserve to tolerate resection, disease confined to the liver, and small
(3 cm), solitary tumors without evidence of vascular
invasion. There is growing evidence that laparoscopic
resection of HCC can be performed safely with equivalent
oncological outcomes compared with open surgery and
with lower perioperative morbidity, particularly in
patients with cirrhosis [21,22]. Although risk of recurrence is higher, surgery may still have a role in the
management of larger, multifocal tumors and disease
associated with vascular invasion [19,23,24].
The presence of lymph node metastasis in patients with
HCC is a poor prognostic factor. The presence of pathologically proven lymph node metastasis in the absence of
distant metastatic disease was found in one recent study
to be associated with an outcome similar to locally
advanced disease [25]. Other studies of patients with
HCC who have undergone curative hepatic resection
and lymph node resection have shown similar
results [26]. However, the role and clinical impact of
routine regional lymphadenectomy in patients with
HCC remain under debate. For patients without cirrhosis
undergoing resection of HCC, lymph node dissection can
provide important staging and prognostic information.
However, in patients with cirrhosis, lymph node excision
can impair lymphatic drainage and increase the risk of
postoperative ascites [27]. The possible benefits of lymph
node excision need to be balanced against this added risk.
Among patientswith HCC with advanced cirrhosis who
are not candidates for resection, orthotopic liver transplantation can be considered for selected patients. The
benefits of liver transplantation include the removal of
both tumor and underlying diseased liver. In a landmark
study by Mazzafero and colleagues, liver transplantation
was associated with a four-year overall survival rate of
85% and a recurrence-free survivalrate of 92% in patients
with HCC and a single lesion 5 cm or up to three tumors,
each 3 cm, and no evidence of vascular invasion and no
nodal metastatic disease [28]. These criteria, known as the
Milan criteria, have been used widely in the selection of
patients for liver transplant although efforts are being
made to expand the indications for transplantation.
For patients with small HCCs who are poor surgical
candidates because of impaired liver function or other
serious medical comorbidities, local ablative therapy with
techniques including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), laser, and microwave
thermal ablation can be considered. RFA has become a
more widely used option since recent studies have shown
superior outcome with RFA compared with PEI, particularly for tumors >2cm [29–31]. RFA also has been com-
pared to surgical resection for HCC in several randomized
trials. The results have varied, with some studies demonstrating superior overall survival and recurrence-free survival rates for patients undergoing surgery [32] and others
showing no differences in survival between the two treatment groups [33,34]. A recent meta-analysis of 10 randomized controlled trials or large cohort studies comparing
percutanous ablation therapy with surgical resection for
early-stage HCC demonstrated improved overall survival
and recurrence-free survival with surgery [35].
12.2.1.1 Neoadjuvant and adjuvant strategies
Unfortunately, only 10–30% of patients with HCC are
candidates for surgical resection at the time of diagnosis,
andrecurrentHCCisreportedin50–80% of patients five
years after resection [12,20,36–38]. Most recurrences are
intrahepatic and may reflect local recurrence or development of a second primary lesion. Neoadjuvant approaches,
including regional therapy with transarterial chemoembolization (TACE), have been examined as a means to improve
disease control prior to resection [39–42]. However, neoadjuvant therapy has not been associated with improvement
in overall survival. Furthermore, TACE prior to surgery for
resectable disease has been associated with worse survival,
potentially because of a delay in surgical resection [40–43].
The benefit of adjuvant medical therapy following
resection of HCC is uncertain and remains under investigation. Most HCCs are chemorefractory in nature, and
thus, cytotoxic chemotherapy has no proven benefitfollowing surgical resection. Furthermore, in patients with
cirrhosis,an increasein mortalityrelated to administration
of postoperative therapy has been demonstrated [44,45].
Sorafenib, a small molecule tyrosinekinaseinhibitorthat
blocks Raf signaling and vascular endothelial growth factor
recptor (VEGFR), platelet-derived growth factor (PDGF),
and c-kit, has been shown to improve overall survival in
patients with advanced HCC [46–48]. Cases have been
reported of significant necrosis associated with sorafenib
use and subsequent ability to resect HCC [49]. However, the
188 Chapter 12
absence of significant tumor response decreases the likelihood of surgery for initially unresectable HCC following
treatment with sorafenib. The benefit of adjuvant sorafenib
was investigated in the STORM study, an international,
randomized, phase III study of sorafenib versus placebo
following surgical resection or local ablation of HCC. No
difference in recurrence-free survival, time to recurrence or
overall survival was observed with administration of adjuvant sorafenib compared with placebo [50]. Thus, there is
no role for sorafenib following resection of HCC.
12.2.2 Management of intermediatestage HCC
Transarterial chemoembolization is a widely used treatment option for patients with intermediate-stage HCC
who have relatively well-preserved liver function, large
(>5 cm) or multifocal tumors without main portal vein
occlusion or the presence of extrahepatic disease [3,12]. A
survival benefit for TACE has been demonstrated in two
randomized controlled trials. In the first study, Llovet and
colleagues found that TACE with doxorubicin was associated with improved overall survival compared with best
supportive care in patients with unresectable HCC and
Child–Pugh class A or B liver dysfunction. The one- and
two-year survival probabilities were 82% and 63% in
patients treated with TACE compared with 63% and 27%
of patients receiving a supportive care approach [51].
Similarly, in a second study of patients with unresectable
HCC, Lo and colleagues found that TACE with cisplatin
and lipiodol was associated with a 57% and 31% one- and
two-year survival, compared with 32% and 11% for
patients receiving supportive care [52]. Despite these
promising results, TACE has not been associated with
improved overall survival (OS) in other randomized
clinical trials [53,54]. Other embolization techniques,
including drug-eluting beads TACE and yttrium-90 radioembolization, and external beam radiation have demonstrated encouraging antitumor activity in patients with
unresectable, intermediate-stage HCC [55–59].
Sorafenib has also been investigated as an adjunct to
chemoembolization. Po st-TACE administration of sorafenib was associated with improved time to tumor
progression (TTP) in a randomized phase II study of
patients with hepatitis C and intermediate-stage HCC
randomized to receive postproced ure sorafenib or placebo (9.2 months for sorafeni b versus 4.9 months for
placebo, P < 0.001) [60]. Howe ver, sora fenib foll owing
or concurrent with TACE has not demonstrated
improvement in TTP in other studies [61,62]. Thus,
existing studies suggest modest if any delay in disease
progression with postembolization sorafenib; the survival benefit of adding sorafenib to TACE remains
under investigation.
There is also a growing body of evidence that radiation
therapy can provide sustained local control for HCC not
suited for other locoregional treatments and for disease
associated with portal vein thrombus [58,59,63,64]. A
recent phase II study examining high-dose hypofractionated proton beam radiation therapy for patients with
locally advanced, unresectable HCC and intrahepatic
cholangiocarcinoma demonstrated a high two-year local
control rate of 94.8% for patients with HCC, supporting
further studies on radiation in patients with primary liver
cancers [64]. Whether improved local control will translate into an improvement in overall survival still needs to
be determined. Finally, the questions of which patients
benefit most from radiation and where radiation fits
within the spectrum of other local therapies for HCC
remain under investigation.
12.2.3 Advanced-stage HCC
12.2.3.1 Systemic chemotherapy
Cytotoxic chemotherapy has modest efficacy against HCC,
which has been attributed to inherent chemoresistance
related to upregulation of multidrug resistance genes and
drug efflux mechanisms [65–67].Furthermore,chemotherapy may not be well tolerated in patients with signifi-
cant underlying liver dysfunction because of altered drug
metabolism and medical comorbidities. Finally, a benefitof
therapy may be difficult to ascertain owing to the poor
survival of patients related to advanced liver disease. Doxorubicin has been the most widely investigated cytotoxic
chemotherapeutic agent for advanced HCC. Despite a modest objective response rate of 20% or less, two controlled
trials have suggested that doxorubicin may be associated
with a small survival advantage than either best supportive
care alone or noletrexed, an inhibitor of thymidylate
synthase [68,69].
Many other cytotoxic chemotherapy agents, including
gemicitabine [70,71], irinotecan [72], paclitaxel [73],
and capecitabine [74], have been tested in HCC in phase
II studies. Response rates ranging from 10% to 30%
have been reported, but no clear effect on survival has
been identified. Combination chemotherapy, with a
regimen such as cisplatin, interferon, doxorubicin, and
5-fluorouracil (PIAF), may be associated with a higher
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