Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1444_Библиотеки_им_академика_М_И_Перельмана.pdf
111
INTRODUCTION
Surgical resection remains the rst-line treatment of appropriately selected
patients with primary and metastatic liver cancer. Until the last two
decades, hepate ctomies were considered operations of prohibitive risk with
frequent hemorrhagic events and high rates of complications and death.
Even as surgeons have pushed the limits with resectability criteria, the
overall mortality rate has fallen signicantly from 10–20% to around 2.5%
nationally. is mortality decrease is the result of more advanced surgical
techniques, better patient selection and risk stratication, optimization
of the future liver remnant (FLR) (including the use of portal vein embo-
lization [PVE] and limiting preoperative chemotherapy), multidisciplinary
treatment strategies, and better diagnostic and therapeutic capabilities to
rescue patients after complications. is chapter focuses on the preopera-
tive considerations a surgeon must evaluate before performing a hepatic
resection.
ANATOMY
In 1888, Rex described the anatomy of the portal vein and the main plane
dividing the left and right liver along the middle hepatic vein. His detailed
illustrations based on embryology set the stage for modern segmental
anatomy (Fig. 10.1). In 1954, Couinaud divided the liver into four sectors
based on the right, middle, and left ssures, which follow the vertical
planes of the three hepatic veins (Fig. 10.2). ey include the right pos-
terior (segments VI + VII), right anterior (segments V + VIII), left medial
(segments III and IV), and left lateral (segment II) sectors. e transverse
scissura follows the plane of the portal vein, which then divides the sectors
into each segment.
e International Hepatopancreatobiliary Association (IHPBA) con-
sensus Brisbane (2000) classication for liver surgery terminology is now
widely adopted, with the liver divided into sections rather than sectors.
e main dierence is that segments II and III now belong together as
the left lateral section with segment IV remaining as the medial segment
without segment III (Fig. 10.3). In an eort to standardize terminology
among surgeons and surgical literature, the terms right/left lobectomy,
bilobar, and trisegmentectomy are now mostly replaced with the terms
right/left hepatectomy, bilateral, trisectionectomy, sectionectomy, and
segmentectomy. Detailed knowledge of the segmental and vascular anat-
omy is critical to preoperatively planning the amount of liver parenchyma
that will need to be resected and how much FLR will remain after resec-
tion. Precise terminology is critical for communication among surgeons,
radiologists, and the multidisciplinary team.
Liver Anatomy, Physiology,
and Preoperative Evaluation
Ching-Wei D. Tzeng and Jean-Nicolas
Vauthey
10
Section II / Liver112
PHYSIOLOGY
For safe resection, the liver parenchyma must have sucient size, adequate
synthetic function, unimpaired biliary drainage and perfusion, and su-
cient regenerative capacity. A global assessment of parenchymal quality is
important to determine the functional ability of the liver to tolerate resec-
tion and to guide the surgeon in choosing a safe maximum volume that can
be resected. is can involve the patient’s history, physical exam, biochemi-
cal tests, and radiologic imaging.
For patients with cirrhosis, the Child-Pugh score classies the sever-
ity of chronic liver disease. is score incorporates albumin, ascites, bili-
rubin encephalopathy, and international normalized ratio (INR) and, by
using a scoring system, straties three classes of mortality risk (Table 10.1).
Usually, only Child-Pugh A patients are considered operable because the
FIGURE 10.1 Intrahepatic portal vein anatomy as depicted by Rex in 1888.
Chapter 10 / Liver Anatomy, Physiology, and Preoperative Evaluation
113
pathophysiologic consequences of cirrhosis are minimal, and thus they are
described as “compensated.” Some surgeons will operate on Child-Pugh B
patients but with a known increased perioperative risk. e operative mor-
tality of Child-Pugh C patients can approach 50% even for “minor” general
surgery operations such as umbilical hernia repair and cholecystectomy.
Child-Pugh C patients cannot tolerate any liver resection. e best treat-
ment for hepatocellular carcinoma (HCC) in patients with Child-Pugh B
and C cirrhosis is liver transplantation if they qualify.
An alternative system for grading cirrhosis is the Model for End-Stage
Liver Disease (MELD), which consists of bilirubin, creatinine, INR, and liver
disease etiology, in a formula originally created to predict 3-month mor-
tality after a transjugular intrahepatic portosystemic shunt (TIPS) proce-
dure and validated for predicting mortality in hospitalized and ambulatory
patients awaiting liver transplant. As an alternative to Child-Pugh score,
MELD score can be used to predict perioperative and long-term mortal-
ity after resection of HCC. While patients with high MELD scores (≥
9) are
inoperable for surgical procedures other than transplant, those with MELD
scores less than 9 can be considered for hepatectomy.
While these rules of thumb are easy to follow if a diagnosis of cirrhosis
already exists, the real clinical problem occurs when chronic liver disease
is unrecognized until surgical exploration. us, patients should be care-
fully screened preoperatively for cirrhosis and portal hypertension based on
history (jaundice, hepatitis, upper gastrointestinal [GI] bleeding, encepha-
lopathy), physical examination (skin varices or supercial venous collater-
als, ascites, mental examination), serum laboratory tests (bilirubinemia,
thrombocytopenia, anemia from bleeding), and imaging (ascites, spleno-
megaly, scalloping of the liver, left lateral section and caudate hypertrophy,
intra-abdominal varices, and venous collaterals). In general, patients with a
bilirubin greater than 2mg/dL are not considered for resection. In patients
who present with obstructive jaundice, resection is only considered after
resolution of the jaundice using preoperative endoscopic or percutaneous
biliary drainage.
Because there is a sliding scale of FLR volume minimums and liver
quality, liver biopsy can be used to diagnose preexisting liver damage and
FIGURE 10.2 Liver segments numbered clockwise from I to VIII and sectors (dotted lines)
along the planes of the three hepatic veins as described by Couinaud. (Adapted from
Couinaud C. Lobes et segments hepatiques: notes sur l'architecture anatomiques et chirur-
gicale du foie. Presse Med 1954;6(2):709–712.)
Section II / Liver114
FIGURE 10.3 Resection planes using the International Hepatopancreatobiliary Association
(IHPBA) Consensus Brisbane (2000) classication for liver surgery. (Adapted from Abdalla EK,
Denys A, et al. Total and segmental liver volume variations: implications for liver surgery.
Surgery 2004;135(4):404–410.)
Child-Pugh score for cirrhosis
10.1
TABLE
1 point 2 points 3 points Class
Albumin (g/dL) > 3.5 2.8–3.5 < 2.8 A: 5–6 points
Ascites None Yes, controlled Yes, refractory B: 7–9 points
C: 10–15 points
Bilirubin (mg/dL) < 2 2–3 > 3
Encephalopathy None Grade I–II
(controlled)
Grade III–IV
(refractory)
INR < 1.7 1.71–2.20 > 2.20
INR, international normalized ratio.
From Child CG, The liver and portal hypertension. Philadelphia, PA: Saunders, 1964.
Chapter 10 / Liver Anatomy, Physiology, and Preoperative Evaluation
115
evaluate whether this damage is acute, subacute, or chronic in nature
(Fig. 10.4). Preoperatively, this can be easily done percutaneously. Or, if
diagnostic laparoscopy is being performed for staging or for another minor
procedure, a wedge biopsy can be done simultaneously. However, as sim-
ple as a biopsy may seem, two major problems must be recognized. First,
the distribution of parenchymal diseases, such as brosis, steatosis, and
chemotherapy-associated liver injury (CALI) such as sinusoidal obstruc-
tion syndrome (SOS) and steatohepatitis (SH), is heterogeneous, and thus
a small liver biopsy can be associated with false-negative results. Secondly,
these histopathologic diagnoses do not accurately predict postresection
liver function, FLR regenerative capacity, and protection from postopera-
tive hepatic insuciency (PHI). us, while a positive liver biopsy may be
helpful, caution should still be exercised if the biopsy is “normal” but the
liver looks clinically damaged. Some parenchymal changes such as fatty
liver can be grossly evaluated with cross-sectional imaging by comparing
the tissue perfusion and attenuation to that of the spleen and abdominal
fat. Many cirrhotic changes from portal hypertension are also readily appar-
ent on imaging as aforementioned. Current work is being done to more
precisely correlate computed tomography (CT) and magnetic resonance
imaging (MRI) ndings with pathologic parenchymal changes.
Indocyanine green retention rate at 15 minutes (ICG R15) is used
as a global measure of liver function. In this test, faster clearance (lower
retention percentage at 15 minutes) implies better liver function and
drainage. Used extensively in East Asia but less so in North and South
America and Europe, a decision tree known as the Makuuchi criteria is
used to evaluate livers with possible chronic disease before minor hepa-
tectomy ( usually for HCC). e qualitative cuto values of ICG R15 may be
less helpful in stratifying livers for major hepatectomy when compared to
regeneration criteria such as those provided by PVE (see below). ICG R15
cutos for wedge resection and segmentectomy are 30% to 39% and 20%
to 29%, respectively. Left hepatectomy or sectionectomy requires 10% to
19% retention or less. Finally, right or extended hepatectomy is consid-
ered only if ICG R15 is less than 10%. An important initial consideration
in applying these criteria is that patients with ascites and/or elevated bili-
rubin (> 2 mg/dL) do not qualify for any type of resection irrespective of
the ICG cutos.
FIGURE 10.4 Diagram of the future liver remnant required for hepatectomy depending on
the parenchymal quality and any preexisting liver injury. (BMI, body mass index).
Section II / Liver116
PREOPERATIVE EVALUATION
Risk Factors for Complications
Complications specic to liver surgery include bleeding (both intraopera-
tive and early postoperative), bile leak, and postoperative hepatic insu-
ciency (PHI or liver failure) with PHI-related mortality. e current authors
previously dened PHI as a peak total bilirubin greater than 7mg/dL, which
has a sensitivity and specicity of greater than 93% and an odds ratio of
10.8 for predicting 90-day mortality. Acute PHI often leads to an irreparable
slide toward liver failure–related mortality that continues well past 30 days.
In regard to measuring surgical outcomes, one-third of posthepatectomy
deaths occur between 30 and 90 days, so typical short-term metrics fail to
fully capture late liver-related mortalities.
Predictors of major complications can be divided into three catego-
ries—medical comorbidities, laboratory abnormalities, and perioperative
risk factors (including extent of hepatectomy). ese parameters include
low albumin, smoking, American Society of Anesthesiologists (ASA) class,
elevated alkaline phosphatase, elevated partial thromboplastin time (PTT),
extent of hepatectomy, prolonged operative time, and intraoperative or
postoperative transfusions. e last three factors are associated with each
other, and thus, surgeons should be cautious with patient selection when
pairing major simultaneous operations with major hepatectomies. While
not every risk factor is reversible, many are potentially modiable in the
preoperative period through optimization of medical issues and planning
operations of lesser magnitude when oncologically practical.
Initial Assessment
e initial preoperative assessment of a patient requiring a liver resection
takes into account three major factors—patient operability (performance
status and comorbidities), liver quality (global function), and tumor extent
(balance of oncologic resectability and FLR). An irreversible or unmodi-
able issue with the patient or the liver precludes liver resection. e risks
of liver resection and PHI are relatively unique, because the liver is the only
abdominal visceral organ without which a patient cannot survive. us,
unless a transplant is planned, enough functional parenchyma must be left
behind, or the patient will inevitably die from liver failure.
Patient Operability
e term “operability” describes patient, not tumor, factors. Patients can
be operable, inoperable, or borderline operable if they have potentially
reversible comorbidities. Operability is dependent on a patient’s func-
tional capacity (performance status) and underlying medical comorbidi-
ties. If both are good, then the patient is operable. If either is irreversibly
poor, then the patient is inoperable. If functional or medical issues are
potentially reversible, then the patient is considered borderline oper-
able. e fact that grading performance status is part of the National
Comprehensive Cancer Network (NCCN) preoperative assessment for
hepatocellular carcinoma (HCC) highlights the importance of assessing
patient operability. With aggressive prehabilitation, nutritional coun-
seling, and/or medical optimization, a borderline operable patient may
become an operable surgical candidate and has the potential to enjoy the
same survival benet from resection as a patient who was initially opera-
ble. If a patient is undergoing preoperative chemotherapy, this time period
oers an opportunity to address the aforementioned issues. Even if pre-
operative therapy is not considered or not indicated, taking appropriate
time to optimize patient physiology before surgery will not only decrease
Chapter 10 / Liver Anatomy, Physiology, and Preoperative Evaluation
117
surgical complications but will also improve the clinical rescue rate of
patients after major complications and decrease the postcomplication
mortality rate.
Assessment and Optimization of Future Liver Remnant
e FLR is the predicted volume of remaining liver after resection. Sucient
size, synthetic function, biliary drainage, perfusion, and regenerative capac-
ity are essential to avoid both early and late PHI. Evaluating the FLR’s
volume is currently the most reliable approach to predict outcomes for
patients who are candidates for major resection. Several methods for such
evaluation have been described. At the University of Texas MD Anderson
Cancer Center (MDACC), the estimated total liver volume (TLV) is calcu-
lated using a formula that relies on the linear correlation between the TLV
and body surface area (BSA): TLV (in cm
3
) = − 794.41 + 1,267.28 × BSA (m
2
).
e “standardized” FLR is then calculated as the ratio of the predicted FLR
volume to the standardized TLV.
In a series of 301 patients without hepatic injury or chronic liver disease
undergoing extended right hepatectomy, a standardized FLR of less than
20% was a risk factor for PHI and 90-day postoperative mortality. Generally,
the required minimum standardized FLR is greater than 20% for normal
livers, greater than 30% for livers with limited parenchymal injury (e.g.,
extended duration chemotherapy), and greater than 40% for permanently
damaged livers (e.g., cirrhosis, Fig. 10.4). Because chemotherapy is used in
the majority of cases of colorectal liver metastases (CLM) and often sev-
eral months of chemotherapy have already been given before the patient
sees a liver surgeon, it is imperative that a liver surgeon understands the
side eects of oxaliplatin and irinotecan, which, along with 5-uorouracil,
have been the backbone of chemotherapy regimens for CLM since the early
2000s (Table 10.2).
With increased CT volumetry availability, “eyeballing” a CT scan
to estimate FLR is highly discouraged. Even with no liver damage, up to
75% of patients at initial presentation are anatomically too small for an
extended right hepatectomy based on the volume of segments II
+
III.
P
reoperative PVE allows a functional stress test to observe the regenera-
tive capacity of the FLR before, rather than after, a hepatectomy. During
a brief 5 weeks between PVE and hepatectomy, surgeons can evaluate the
degree of hypertrophy (DH; needs to be > 5%) and the kinetic growth rate
(KGR = DH divided by time in weeks). Patients with a KGR less than 2% may
be spared hepatectomies of excessive extent that would leave inadequate
FLR. Not all PVEs result in adequate hypertrophy, and one putative criti-
cism of PVE is inadequate hypertrophy preoperatively. However, with PVE
Agent Liver Changes Clinical Sequelae
Oxaliplatin • Sinusoidal dilation
• Sinusoidal obstructive
syndrome (SOS)
• Microvascular damage
• Increased perioperative
transfusions with > 6 mo of
preoperative chemotherapy
Irinotecan • Steatosis
• Steatohepatitis
• Increased complications
• Increased overall 90-d mortality
(15%) and liver failure–related
mortality (6%)
10.2
Chemotherapy-Associated Liver Injury Characteristics
TABLE
Section II / Liver118
of the right portal vein and segment IV with the combined use of spherical
microspheres and coils, an FLR increase of 69% has been documented in
the hands of experienced interventional radiologists.
Tumor Extent and Resectability
Besides patient operability, whether a liver tumor can be resected is depen-
dent upon two other major factors—technical resectability and oncologic
feasibility. Technical resectability is the ability to surgically remove all liver
tumors with R0 (negative microscopic) margins while leaving adequate
FLR. Adequate FLR must have regenerative capacity and consist of at least
two functional contiguous liver segments with biliary drainage and vascu-
lar inow/outow. Again, tumor resectability should be dierentiated from
patient operability, which is the patient’s physiologic and medical ability to
undergo and recover from major abdominal surgery.
Oncologically, resectability is determined by the tumor biology of the
cancer type and the individual patient. For example, while extrahepatic
disease is a contraindication for resection in primary liver cancer, patients
with limited extrahepatic disease in controllable sites (e.g., small lung
metastases or regional lymph nodes) can still benet from hepatectomy
for CLM. However, because these patients are biologically at higher risk of
recurrence, they need perioperative chemotherapy. Even patients with lim-
ited progression of preexisting CLM while on preoperative chemotherapy,
but whose lesions remain anatomically resectable, should undergo resec-
tion. However, patients who develop new lesions or interval extrahepatic
disease while on preoperative chemotherapy should not undergo surgery
until the systemic disease is controlled.
Preoperative Planning with Radiographic Imaging
Four major imaging options are used for liver tumors—ultrasound (US),
CT, MRI, and positron emission tomography/CT (PET/CT). US is inexpen-
sive and reliable, but has been replaced by cross-sectional imaging due to
limited image reproduction, operator variability, and decreased ability to
detect small lesions. However, intraoperative US (IOUS) remains a critically
important surgical tool, because it can nd additional tumors not seen on
preoperative cross-sectional imaging in up to 10% of patients, even with use
of improved high-resolution CT and MRI. e greatest value of IOUS is in
guiding the resection in relation to hepatic vascular anatomy and directing
parenchymal transection to balance optimal tumor margins with maximal
FLR preservation.
e current standard for preoperative planning is high-resolution,
contrast-enhanced multidetector CT of the chest, abdomen, and pelvis.
For enhanced liver characterization, MRI abdomen and pelvis with chest
CT is an alternative. CT is generally more useful than MRI for comprehen-
sive imaging for staging, including chest and other abdominal structures.
In general, CLM are hypovascular and more prominent in the portovenous
phase as hypodense lesions. On the other hand, HCC are hypervascular on
the arterial phase with washout on delayed images. Although suboptimal
for general abdominal and chest surveillance, MRI is useful for diagno-
sis and staging of liver tumor burden. Using multiple and newer contrast
agents and dynamic phases, high-resolution (3-tesla) MRI oers increased
lesion characterization over CT, especially for subcentimeter indet erminate
lesions. If preoperative chemotherapy is administered, whichever modality
was chosen pretreatment should be repeated after preoperative treatment
and before liver resection for accurate FLR assessment.
ere has been a recent dramatic increase in the use of PET/CT to
identify areas of increased metabolic activity, which are often presumed
Chapter 10 / Liver Anatomy, Physiology, and Preoperative Evaluation
119
to be metastases in patients with cancer. Unfortunately, PET can also be
nonspecic, and the matched noncontrast CT adds little information for
equivocal areas, prompting additional workup. At MDACC, PET/CT is
reserved for the detection of occult extrahepatic disease in patients with a
high index of suspicion for metastatic disease and equivocal cross-sectional
imaging (e.g., elevated carcinoembryonic antigen [CEA] with normal CT)
when detection would change the planned treatment strategy.
Percutaneous needle biopsies of suspected liver tumors are unnec-
essary when imaging identies new lesions with characteristic imaging
features for metastases or primary liver cancer. Needle biopsy may be
appropriate when a benign lesion is suspected and cannot be delineated
noninvasively with MRI and again importantly, only if the treatment plan
would change based on the result.
Radiographic evaluation of treatment response has prognostic value
and frequently determines resectability. Although traditionally measured
by Response Evaluation Criteria in Solid Tumors (RECIST) and modied
RECIST criteria, change in tumor diameter may not provide the best prog-
nostic information. Besides using disease-free interval and tumor factors
from published clinical risk scores, biologic selection can be accomplished
by stratifying patients by the morphologic response on CT after preopera-
tive treatment for CLM. e morphologic response did not correlate with
size-based RECIST measurements, and it was better than RECIST at pre-
dicting major pathologic response. When tumors change from heteroge-
neous consistency and irregular borders to homogenous density, clearly
demarcated borders, and no enhancement, this pattern strongly corre-
lates with pathologic response, margin control, and survival (Fig. 10.5).
Suboptimal morphologic response is an independent predictor of worse
overall survival and thus may oer the surgeon and the patient important
prognostic information when counseling about the potential risks versus
benets of hepatectomy. Figure 10.5 details the optimal 1 morphologic
response seen in a patient who underwent preoperative chemotherapy for
a very large liver metastasis, which encased the right and middle hepatic
veins. With such good morphologic response, undergoing the risk of an
extended right hepatectomy made oncologic sense in that he was the type
of patient who might benet the most from resection. After PVE, he under-
went a margin-negative extended right hepatectomy and is alive more than
5 years later.
PREOPERATIVE THERAPY AND DOWNSIZING
When patients present with anatomically unresectable CLM, the clinician
should consider the ability to downsize their lesions to resectability crite-
ria. Eective chemotherapy may achieve this goal in 10% to 20% of initially
unresectable patients, and patients who make it to resection share survival
rates far better than those associated with palliative chemotherapy with
outcomes approaching that of patients with initially resectable CLM. To
convert patients from unresectable to resectable, maximal tumor response
is required (unlike the goal for preoperative chemotherapy for resectable
lesions), frequently involving the addition of targeted agents. With these
agents, the conversion rate from unresectability to resectability can be as
high as 13% to 23%.
After downsizing with chemotherapy and targeted therapy, the sur-
gical goal should be an R0 resection of all known sites of CLM, including
known original sites of any lesions that disappeared with complete radio-
graphic response. A recent “problem” due to improving ecacy of systemic
chemotherapy, patients are sometimes presenting to the liver surgeon with
Section II / Liver120
FIGURE 10.5 Optimal response to preoperative chemotherapy. Despite having a positive
portal lymph node, this patient was alive with no evidence of disease at 5 years. He has an
optimal morphologic (loss of enhancement and well-dened lesion) response during preop-
erative chemotherapy (from A to B). His postoperative scan revealed excellent hypertrophy
after extended right hepatectomy following preoperative portal vein embolization (C).