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191
time (PT)/ international normalized ratio (INR), degree of ascites and degree of
hepatic encephalopathy assigning 1–3 points for each variable. Patients are divided
into three classes based on total points with 6, 7–9, and 10 points representing
Child’s class A, B, and C, respectively. Unlike the CTP score which contain variables that are somewhat subjective, the MELD score, a linear regression model
based on patient’s serum creatinine, total bilirubin and INR, was initially designed
to predict mortality in cirrhotic patients who were undergoing transjugular intrahepatic portosystemic shunts ( TIPS ) [ 9 ]. Subsequently, the model has been validated
prospectively as a prognostic tool in patients awaiting liver transplant ation [ 10 ].
This model also effectively predicts mortality in patients who underwent nontransplant surgery [ 11 ].
Search Strategy
A literature search of the English language publications from 1990 to 2014 was
used to identify published data on the use of Child Class and/or MELD score as a
predictor of hepatic reserve prior to liver resection using the PICO outline
(Table 16.1 ). The databases searched included PubMed, Science Citation Index/
Social Sciences Citation index, Embase, and Cochran Evidence Based Medicine .
Keywords used for the search included “MELD score,” Child score/classifi cation,”
“Child- Pugh score/classifi cation,” “Child-Turcotte-Pugh score/classifi cation,” “ cirrhosis ,” AND “liver resection ,” OR “ hepatectomy .” Articles were classifi ed using
the GRADE system.
Liver Resections and the Childs-Turcotte-Pugh Score
CTP score has been applied to liver resection in an attempt to predict hepatic reserve
and mortality post liver resection . It is fairly well established that patients with
Class C cirrhosis poorly tolerate resection. An early study by Nagasue et al. documented their experience with 63 patients (46 Class B and 17 Class C cirrhotics). In
their series, they had a 17.6 % overall peri-operative mortality (30 days from surgery ) for their class C patients and a 23.5 % in-hospital death rate [ 12 ].
Table 16.1 PICO table for assessment of hepatic reserve prior to liver resection
P (Patients) I (Intervention) C (Comparator group) O (Outcomes measured)
Patients with
cirrhosis
undergoing
hepatic
resection
Use of MELD
scoring system
preoperatively to
assess hepatic
reserve
Use of the ChildTurcotte-Pugh
classifi cation to assess
hepatic reserve prior to
liver resection
Incidence of liver dysfunction/
failure post liver resection
resulting in increased length of
stay, hospital cost, morbidity,
and mortality
16 Which Is the Better Predictor of Hepatic Reserve Prior to Liver Resection…
192
Few studies also focus on class B cirrhotics with even fewer giving a detailed
analysis of peri-operative morbidity . Two studies were identifi ed which focused on
outcomes following resection of class B cirrhotics. The fi rst series by Nakahara
et al. examined 119 patients with HCC who underwent resection that were identifi ed as class B cirrhotics [ 13 ]. Of these patients, >75 % of them underwent a limited
resection (less then a segmentectomy). In this series, the in-hospital mortality was
5 %, with two patients suffering from liver failure in the immediate postoperative
setting. Multivariate analysis revealed risk factors for poor outcome which included
elevated bilirubin (>1.5 mg/dl) and the presence of ascites [ 13 ]. Similarly, Kuroda
et al . studied 150 class B cirrhotics. Although the risk of immediate post-operative
liver failure appears to be low in these patients, many patients ultimately die of liver
failure (15 %) [ 14 ]. Based on these studies, limited resection can be performed on
patients with CTP Class B cirrhosis with caution but major resections should be
avoided.
One would predict that class A cirrhotics would have less post-operative liver
dysfunction and liver failure based on the fact that Class A patients by defi nition
have minimal symptoms (if any) of chronic liver disease. The majority of large
published studies focus on patients with class A cirrhosis and HCC . However, studies have clear bias and show improvement in outcomes over time but little change
in the number of patients with cirrhosis [ 15 ]. Even for patients with class A cirrho-
sis, the range of liver function appears to vary widely as judged by ICG retention
studies performed on Class A patients [ 16 ]. In a series of 625 patients resected for
HCC, CTP was not found to be an independent predictor of perioperative morbidity
[ 17 ]. In contrast, Nagasue et al. reported their outcomes of 229 patients and found
that CTP was predictive of post-operative complications. In this series, only patient
with cirrhosis were at risk for developing post-operative liver failure [ 18 ]. In a large
European study, all patient resected were considered Class A but they noted a 32 %
incidence of post-operative liver failure in patients with stage 4 fi brosis (cirrhosis)
[ 19 ].
The extent of liver resection is obviously an important predictor of post- operative
liver dysfunction and liver failure . Two studies were identifi ed which focused on
major hepatic resection s and CTP classifi cation. Yang et al. specifi cally examined
outcomes of patients with cirrhosis following major hepatic resection [ 20 ]. In this
series, 270 patients had class A cirrhosis versus 35 with class B cirrhosis. Risk factors for preoperative morbidity were the presence of portal hypertension, Child
class B, and platelet count <100 × 10 9 /l. However, independent risk factors for
postoperative hepatic dysfunction were a prothrombin time >14 s and a platelet
count <100 × 10 9 /l, not CTP score. In addition, four patients died of post-operative
liver failure of which two were Class A cirrhotics. Similarly, Zhou et al. examined
their experience after major hepatectomy in 81 patients of which 6 (7.4 %) had class
B cirrhosis and only one patient suffered perioperative hepatic failure [ 21 ].
Based on the current available literature, Class C cirrhosis should be an absolute
contraindication to resection . On the other hand, resection in Class A and B cirrhosis is not an absolute contraindication, but these patients should be selected carefully in order to minimize post-operative complications. In addition, the magnitude
T.W. Reichman and H. Bohorquez
193
of resection required for cure should be carefully considered when selecting suitable patients for hepatic resection .
Liver Resections and the Meld Score
MELD has been applied to cirrhotic patients who underwent liver resection for
hepatocellular carcinoma ( HCC ) for more than a decade. Marrero et al. in a subgroup of ten patients fi rst reported that MELD score correlates with post-operative
survival in patients who underwent liver resection for HCC and found that a MELD
score >10 was indicative of poor prognosis [ 22 ]. Similarly, Teh et al . retrospectively
analyzed 82 cirrhotic patients who underwent liver resection for HCC [ 23 ]. A
MELD score 9 was an independent predictor of perioperative mortality (0 % in
patients with MELD score 8 vs. 29 % with MELD score 9). In another study with
154 liver resections, Cuchetti et al. demonstrated that MELD score not only predicts
accurately postoperative liver failure , complications, and survival but that is also
helpful stratifying the risk [ 24 ]. When the patients were analyzed in three groups
according to their MELD score, <9, 9–10 and 11, postoperative liver failure
occurred in 0, 3.6 and 37.5 % respectively. A MELD score cut-off of <9 for
mortality- morbidity for liver resections in cirrhotic patients has been confi rmed by
others [ 25 – 27 ].
AASLD and EASL guidelines recommend liver resection for HCC patients with
solitary tumors and well-preserved liver function defi ned as normal bilirubin, platelets >100,000/mm 3 and hepatic pressure <10 mmHg [ 28 , 29 ]. Cuchetti reviewed this
concept in 241 cirrhotic patients that underwent liver resections and were divided in
two groups according to the presence or absence of portal hypertension [ 30 ]. The
study showed lower survival in those patients with portal hypertension because of
greater liver impairment; however, after propensity score matching of 78 patients,
the overall survival was similar in patients with and without portal hypertension. In
this subgroup of patients, the only predictors of postoperative liver failure were
MELD score and the extent of hepatectomy . They concluded that when other prognostic variables were appropriately handled, the presence of portal hypertension had
no impact on peri-operative outcomes and that the presence of portal hypertension
alone should not be considered a contraindication for hepatic resection .
MELD score has been reported to have low prognostic power in non-cirrhotic or
well preserve hepatic function patients. Schroeder et al. in a review of 587 hepatectomies found no correlation between MELD score and post-operative outcomes
[ 31 ]. However, the majority of the study population (91 %) had minimal or no evi-
dence of liver disease (MELD score 5.7 ± 3.3). A similar smaller study of 46 patients
(21 without cirrhosis vs. 25 with cirrhosis) with HCC who underwent liver resection
demonstrated that MELD score failed to predict perioperative outcomes in the noncirrhotic patients [ 32 ]. By contrast, in the cirrhotic group, the model was able to
predict poor outcomes when MELD was calculated preoperatively and on postoperative day 5 (MELD score >9 and >15, respectively).
16 Which Is the Better Predictor of Hepatic Reserve Prior to Liver Resection…
194
Extent of resection , a major limitation for hepatectomies especially in cirrhotic
patients, also correlates with the MELD score. In a report by Cescon et al., 341 cirrhotic patients were retrospectively evaluated to determine the incidence and factors
that affect irreversible post-operative liver failure (IPLF). In this study, MELD score
and extent of hepatectomy were identifi ed as independent factors of IPLF [ 33 ]. For
analysis, patients were stratifi ed according to their MELD score. In patients with
MELD <9, IPLF occurred in one patient (0.4 %) with four segments resected; in
MELD scores 9–10, IPLF occurred in 1.2 % of patients that underwent resection of
less than one segment, in 5.1 % for 1 or 2 segments resected and in 11 % for 3
segments. In patients with a MELD score >10, IPLF occurred in >15 % of the
patients regardless of the degree of resection. Interestingly, in the group with MELD
scores 9–10, all IPLF cases occurred in patients with a sodium level <140 mEq/L; a
level that seems to defi ne high/low risk groups for liver resection .
The MELD -Sodium (MELD-Na) model, a revised MELD formula that incorporates serum sodium levels, is superior at predicting outcomes in liver transplant ation
especially in those patients with lower MELD scores. Recently, a study successfully
applied the MELD-Na score in predicting morbidity and mortality following elective colon cancer surgery irrespective of underlying liver disease [ 34 ]. Studies are
needed to defi ne whether this parameter could be applied to patients who underwent
liver resection .
The MELD score has also been evaluated against other prognostic tests and
scores to test their ability to determine the functional hepatic reserve in cirrhotic
patients undergoing liver resection . In a study from the University of Toronto, the
MELD score was compared against the use of ICG retention at 15 min (ICG15), a
dynamic test for hepatic functional reserve [ 35 ]. In this study of 129 patients who
underwent liver resection for HCC , ICG15 15 % and MELD score 14 were independent factors to predicts length of stay >10 days. However, MELD score failed to
predict liver failure at post-operative day 3 while ICG15 did. Postoperative survival
was not analyzed. Likewise, in a prospective study that included 40 patients, ICG15
and MELD score correlated with prognosis; however, ICG15 had a higher sensitivity and specifi city than the MELD score, 85 % and 90 % vs. 60 and 80 %, respectively [ 36 ].
Child-Turcotte-Pugh vs. MELD Score
Although the CTP score is easy to use and evaluates major elements of liver function, it has several limitations. Two of the components of the score, ascites and
encephalopathy, are subjective measurements; the score factors are weighted
equally and use arbitrary cut-off. Therefore, CTP score calculation is not always
reliable, and since patients within the same CTP class are not necessarily homogeneous, discrimination of the risk is limited. As a consequence, patients could erroneously be classifi ed and either be exposed unnecessarily to high risk procedures or
excluded from benefi cial therapeutic interventions.
T.W. Reichman and H. Bohorquez
195
By contrast, MELD score is objective, reproducible, weighs its components differently and does not depend on arbitrary cut-offs providing a very useful tool to
predict outcomes in cirrhotic patients. In patients with cirrhosis who underwent
liver resection , preoperative MELD score has been able to not only predict outcomes but also to stratify the risk. Moreover, in patients within the same CTP class
or same level of portal hypertension, the MELD score was able to successfully discriminate the risk and identify appropriate candidates for liver resection. In addition, delta MELD, variations in MELD score at different points of the perioperative
time, is also predictive of morbidity and mortality .
MELD score, however, seems to be limited to cirrhotic patients and fails to predict outcomes in non-cirrhotic patients. In this population, a combination of the
serum sodium level and/or MELD-Na seems to improve accuracy but further studies are required to validate this observation .
There are several limitations to the studies that use CTP and MELD score to
stratify patients for liver resection . First, there is a lack of prospective randomized
control trials. Second, the majority the patients evaluated in different studies were
cirrhotic patients with CTP class A (88–100 %), indicating a selection bias where
liver resection is offered to patients with minimal liver disease. Third, minimal
information is available comparing these scoring systems in non-cirrhotic patients.
Table 16.2 compares major studies examining MELD vs. CTP.
A Personal View of the Data
The currently available literature has a large selection bias and lacks large amounts
of patients with advanced cirrhosis . In our practice, MELD has been found to be the
most predictive of hepatic reserve . However, we rarely use the MELD score in isolation to determine a patient’s candidacy for resection . Other factor not accounted for
in MELD such as the presence of ascites , evidence of portal hypertension on imaging or endoscopic gastroduodenoscopy (EGD), and the platelet count (<100) are
also used in determining the ability of patient to tolerate resection. Detailed volumetric analysis is performed to determine the residual liver volume and also to aid
in planning the resection. If the residual volume appears to be marginal, portal vein
embolization is performed to increase the remnant volume but also to test the regenerative capacity of the remaining liver. Biopsy of the remnant segment is also performed liberally to determine the degree of fi brosis/cirrhosis. For patients with
HCC , if there is any question as to the hepatic reserve of the liver and the patient is
within Milan or close to being within Milan, many of these patients are referred for
transplant evaluation.
16 Which Is the Better Predictor of Hepatic Reserve Prior to Liver Resection…
196
Table 16.2 Studies which compare CTP to MELD
Study Patients
Patients with
cirrhosis
CTP A/B/C
class (%) MELD score Extent of resection
Mortality prognostic
factor
Quality of
evidence
Teh
(2005)
82 100 % 97.5/2.5/0 8 = 37; 9 = 43 range
(6–17)
<3 seg = 72 % 3 seg
= 28 %
MELD score (9) Low
Cuchetti
(2006)
154 100 % 92.9/7.1 9 (range 6–15) Minor = 146 (94.8 %) MELD score (<9, 11) Low
Major 8 (5.2 %)
Schroeder
(2006)
587 N/M 88.2/7.8/0.7 6.51 ± 4.5 range (6–38) 2 seg = 61.4 % CTP score (6.2 ± 1.9)
MELD score = not
signifi cant
Low
Total R/L = 31.7
Triseg = 6.5 %
Cuchetti
(2009)
241 100 % PH = 88.8/11.2/0 PH = 9.5 ± 1.8 1 segment = 81 % MELD score >10 Low
noPH = 98/2/0 noPH = 8.4 ± 1.3 Extent of hepatectomy
2 seg = 14.1 %
Major hepatectomy 4.9
%
Cescon
(2009)
466 100 % 94.2/5.8/0 8.9 ± 1.8 <1 Segment = 45 % CTP B MELD <9,
9–10,>10
Low
>10 (17 %)
1-segmen = 29.6 % Na <140 mEq/L
2 seg = 2.4 Major
hepatectomy 12.4
Extent of hepatectomy
CTP Child-Turcotte-Pugh, MELD Model for End Stage Liver Disease, N/M not measured, N/S not specifi ed, PH portal hypertension, noPH no portal
hypertension
T.W. Reichman and H. Bohorquez
197
Recommendations
• The MELD scoring system is the best at predicting preoperative liver dysfunc-
tion and liver failure with a MELD score of 9 acting as a cutoff (evidence quality
low, weak recommendation)
• Other factors such as extent of resection , presence of portal hypertension, abso-
lute platelet count, and the serum sodium should also be taken into account when
selecting patients with chronic liver disease for resection (evidence quality low,
weak recommendation)
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16 Which Is the Better Predictor of Hepatic Reserve Prior to Liver Resection…
201© 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_17
Chapter 17
Early (<24 h) or Delayed Cholecystectomy
for Acute Cholecystitis?
Stephan G. Wyers
Abstract The optimal timing for operation for acute calculous cholecysitis remains
controversial. Two courses of surgical management have traditionally been pursued:
(1) early laparoscopic cholecystectomy (within the fi rst 72 h of onset of symptoms)
or (2) initial conservative management with administration of intravenous antibiotics
until infl ammation resolves followed by delayed laparoscopic cholecystectomy
(generally greater than 6 weeks after presentation). There is a growing body of
evidence from both retrospective reviews of large clinical databases and prospective
randomized controlled trials to recommend early laparoscopic cholecystectomy
(ELC) over delayed laparoscopic cholecystectomy (DLC).
Keywords Acute cholecystitis • Laparoscopic cholecystectomy • Management •
Timing
The question of optimal timing of any operation necessarily involves an understanding of the natural history of the disease and reference time points in its clinical
course. Acute calculous cholecystitis begins with cystic duct obstruction by a gallstone. Persistence of the obstruction leads to distension of the gallbladder, edema in
the gallbladder wall, infl ammation in the gallbladder wall and adjacent tissues.
After 72 h the infl amed tissue becomes thickened, more vascular and adherent to
surrounding structures making dissection in the hepatocystic triangle more diffi cult.
Delaying cholecystectomy for a period of 6 weeks or longer results in the formation
of fi brotic adhesions in the hepatocystic triangle distorting the anatomy and complicating dissection. The question of timing of operation also requires agreement about
a specifi c clinical event that defi nes the start of the disease process. Various studies
use different clinical events, such as the onset of symptoms reported by the patient
S. G. Wyers (*)
Section of General Surgery , University of Chicago Medicine ,
MC5031, 5841 S. Maryland Avenue , Chicago , IL 60637 , USA
e-mail:
swyers@surgery.bsd.uchicago.edu