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of Gallstones
Kurinchi S. Gurusamy, MRCS*, Brian R. Davidson, FRCS
KEYWORDS
Gallstones Cholelithiasis Choledocholithiasis
Cholecystectomy Surgical procedures Operative
Postoperative complications
Department of Surgery, Royal Free Campus, University College London Medical School, 9th
Floor, Royal Free Hospital, Pond Street, London NW3 2QG, UK
* Corresponding author.
E-mail address: kurinchi2k@hotmail.com
PRIMARY PREVENTION
ASYMPTOMATIC GALLSTONES
ACUTE CHOLECYSTITIS
PANCREATITIS
Gallstone pancreatitis is caused by migration of stones into the common bile duct with
subsequent obstruction to the bile duct, the pancreatic duct, or both.59 This causes
increase in pancreatic duct pressure, resulting in unregulated activation of trypsin
and pancreatitis.59 Gallstones are the most common cause for acute pancreatitis.60,61
The overall mortality of acute pancreatitis is between 3% and 10%.60,61 The role of
early endoscopic sphincterotomy in the management of gallstone pancreatitis is
controversial. Although the total number of complications is fewer after early endo-
scopic sphincterotomy for predicted severe pancreatitis,62 there is no reduction in
either the local pancreatic complications or the overall mortality for predicted mild
or severe pancreatitis.63 There is of no benefit of early endoscopic sphincterotomy
for patients with acute gallstone pancreatitis without cholangitis.64 Irrespective of
the role of endoscopic sphincterotomy in pancreatitis, endoscopic sphincterotomy
alone is not a definitive treatment for common bile duct stones. In a systematic review
of randomized controlled trials, a policy of observation alone after endoscopic sphinc-
terotomy increased the risk of mortality and gallstone-related complications
compared with prophylactic cholecystectomy.65 Hence, cholecystectomy is recom-
mended after an attack of gallstone pancreatitis (grade A). There have been two
randomized controlled trials investigating the timing of cholecystectomy.66,67 In one
trial, the mortality and morbidity were higher when the cholecystectomy was per-
formed within 48 hours of admission compared with cholecystectomy performed after
48 hours of surgery but within the same hospital admission.66 In the other trial, the
patients were operated between 3 days and 14 days after hospital admission for
pancreatitis in the early group and after 3 months in the delayed group.67 There was
no difference in the postoperative mortality or morbidity between the two groups.
Of the nine patients allocated to the delayed group, however, one patient (11%) devel-
oped another attack of pancreatitis, and two patients developed abdominal pain while
waiting for surgery.67 Both these studies were conducted in the era of open cholecys-
tectomy and were underpowered to detect reasonable differences in mortality and
morbidity. There has been no trial on the timing of surgery in the laparoscopic surgery.
For those patients who undergo pancreatic necrosectomy or debridement after failed
percutaneous drainage for infected pancreatic necrosis,68,69 it is reasonable to
perform cholecystectomy at the same time.68 For the remaining patients who do
not require surgical interventions on the pancreas, laparoscopic cholecystectomy
can be performed safely when the general condition improves and can be completed
laparoscopically in 85% to 90% of patients with mild pancreatitis68,70 and in about
60% of patients with severe pancreatitis.68 Cholecystectomy is completed in the
remaining patients by conversion to an open procedure. Some authors recommend
laparoscopic cholecystectomy as soon as the serum amylase and the abdominal
tenderness start to decrease70 rather than waiting for amylase to return to normal
and for the patient to be free from abdominal pain. This approach was based on their
observation that such an approach was safe, did not result in a high rate of conversion
to open cholecystectomy, and resulted in a shorter hospital stay compared with the
traditional early cholecystectomy group (ie, waiting for amylase to return to normal
and relief from abdominal symptoms).70 Considering that early laparoscopic chole-
cystectomy is safe and can be completed successfully in most patients with mild
acute pancreatitis, delaying laparoscopic cholecystectomy seems unnecessary and
can expose the patient to further gallstone-related complications. Thus, cholecystec-
tomy in the same admission appears to be the preferable option in patients with mild
gallstone pancreatitis (grade B). The general condition and the severity of the
234 Gurusamy & Davidson
pancreatic disease will determine the timing of the cholecystectomy in patients with
severe pancreatitis. Cholecystectomy appears safe as soon as the general condition
of the patient improves and the pancreatic necrosis becomes sterile if infected (or
remains sterile if not infected)68 (grade B). Considering that laparoscopic cholecystec-
tomy is safe and seems to be the preferred option (most cholecystectomies in the
United Kingdom and the United States are performed laparoscopically),71,72 laparo-
scopic cholecystectomy can be recommended as the preferred approach in patients
with gallstone pancreatitis (grade B).
OBSTRUCTIVE JAUNDICE
Patients with gallstones develop obstructive jaundice if stones migrate into the
common bile duct. Although common bile duct stones can be removed endoscopi-
cally,73 subsequent cholecystectomy is recommended based on a systematic review
of randomized controlled trials in which a policy of observation after endoscopic
sphincterotomy increased the risk of mortality and gallstone-related complications
compared with routine cholecystectomy65 (grade A). There are no studies investi-
gating the natural history of patients with obstructive jaundice caused by common
bile duct stones. Considering that obstructive jaundice can lead to complications
such as cholangitis, renal dysfunction, cardiovascular dysfunction, and coagulop-
athy,74,75 obstructive jaundice caused by common bile duct stones needs to be
treated as an emergency (grade B). The various options for the treatment of common
bile duct stones include open cholecystectomy with open common bile duct explora-
tion, laparoscopic cholecystectomy with laparoscopic common bile duct exploration,
and laparoscopic cholecystectomy with endoscopic sphincterotomy (performed
preoperatively, intraoperatively, or postoperatively).76,77 A systematic review of
randomized controlled trials has shown that open cholecystectomy with open
common bile duct exploration has the lowest incidence of retained stones76 but is
associated with high morbidity and mortality, particularly in elderly patients.78 There
was no difference in the incidence of retained stones between preoperative and post-
operative endoscopic retrograde cholangiopancreatography (ERCP) and laparo-
scopic common bile duct clearance at the time of laparoscopic cholecystectomy.76
The total hospital stay was shorter in the laparoscopic exploration group.76 One
randomized controlled trial has shown that there is no difference in any of the impor-
tant outcomes between laparoscopic cholecystectomy with laparoscopic common
bile duct exploration and laparoscopic cholecystectomy with intraoperative endo-
scopic sphinterotomy.77 Three trials have shown that intraoperative endoscopic
sphincterotomy is at least as safe and effective as preoperative endoscopic sphincter-
otomy followed by laparoscopic cholecystectomy79–81 and shortens hospital stay.79–81
There was no significant difference in the success rates between preoperative endo-
scopic sphincterotomy and intraoperative endoscopic sphincterotomy.79–81 There
are no trials comparing open cholecystectomy and common bile duct exploration
with laparoscopic cholecystectomy and laparoscopic common bile duct exploration.
There is also no randomized controlled trial comparing open cholecystectomy with
open common bile exploration to laparoscopic cholecystectomy with intraoperative
endoscopic sphincterotomy. Considering that laparoscopic cholecystectomy is
preferred to open cholecystectomy (a significant majority of the cholecystectomies in
the United Kingdom and in the United States are performed laparoscopically),71,72 lapa-
roscopic cholecystectomy along with laparoscopic common bile duct exploration or
intraoperative endoscopic sphincterotomy can be recommended as the preferred
method of treatment of patients with obstructive jaundice due to gallstones where
Surgical Treatment of Gallstones 235
the expertise and infrastructure are available (grade B). When these are not available,
laparoscopic cholecystectomy with preoperative endoscopic sphincterotomy or post-
operative endoscopic sphincterotomy may be the preferred treatment for common bile
duct stones. For patients with impacted common bile duct stone not amenable to lapa-
roscopic or endoscopic clearance, lithotripsy82 or open common bile duct exploration
can be the other options (grade B).
SPECIAL SITUATIONS
High-Risk Individuals
If patients are at high risk of surgery because of pancreatitis, jaundice, or sepsis,
cholecystectomy should be offered once their general condition improves. This is
because of evidence from a systematic review of randomized controlled trials, which
shows leaving the gallbladder in situ after endoscopic sphinterotomy results in an
increased overall mortality65 (grade A). In a randomized controlled trial, percutaneous
cholecystostomy followed by early laparoscopic cholecystectomy (in 3 to 4 days after
the percutaneous cholecystostomy) resulted in a considerable decrease in the
hospital stay compared with delayed laparoscopic cholecystectomy.15 It is not
possible, however, to assess the effect of percutaneous cholecystostomy alone
from this trial. It appears that percutaneous cholecystostomy with early laparoscopic
cholecystectomy is an effective option in patients who are temporarily unwell because
of gallbladder sepsis. The only trial that assessed whether percutaneous cholecystos-
tomy in addition to antibiotic therapy (but without early laparoscopic cholecystectomy)
was of any benefit in high-risk surgical individuals showed that there was no benefit in
performing percutaneous cholecystostomy in patients with acute choleystitis.83 This
study, however, was not powered to measure the difference in mortality, which was
9.1% in the percutaneous cholecystostomy group and 17.7% in the antibiotics-alone
group. Further studies are necessary to assess the role of percutaneous cholecystos-
tomy as a temporary measure in the treatment of high-risk surgical individuals with
acute cholecystitis. In patients who are at high risk of surgery because of comorbid-
ities that will not improve with the treatment of sepsis, surgery cannot be recommen-
ded (grade B).
Cirrhotic
There are few studies that report the natural history of gallstones in cirrhotic
patients.84,85 The frequency of symptoms or complications does not appear to be
any different from other groups of patients with gallstones. When patients develop
complications, however, they can be more severe.85 Cholecystectomy is recommen-
ded for symptomatic gallstones (grade B). There are no differences in the timing of
surgery for various indications between compensated cirrhotic patients and other
patients with symptomatic gallstones. For compensated cirrhotic patients with symp-
tomatic gallstones, laparoscopic cholecystectomy appears better than open chole-
cystectomy, as randomized controlled trials have shown that the laparoscopic
cholecystectomy has similar morbidity as open cholecystectomy86,87 but results in
lower blood loss,86,87 transfusion requirements,86 and hospital stay.86,87 The overall
morbidity and mortality after cholecystectomy, however, are higher in cirrhotic
patients than in noncirrhotic patients.88
Pregnancy
Most pregnant women with gallstones remain asymptomatic during their pregnancy,89
and there is no indication for cholecystectomy. Patients with symptomatic gallstones
236
Table 1
Recommendation
Patient Population Dilemma (Grade of Recommendation) Grade Remarks
Patients at high risk of developing Is surgery No B Applicable in all patients including those
gallstones but currently do not required? undergoing gastrectomy for gastric cancer
have gallstones and gastric bypass for obesity
When? Not applicable -
How? Not applicable -
Asymptomatic gallstones (except those Is surgery No B Applicable in all patients with asymptomatic
undergoing major abdominal surgery) indicated? gallstones including diabetics, sickle cell
disease, and children
When? Not applicable -
How? Not applicable -
Asymptomatic gallstones and Is surgery Yes B Applicable in patients undergoing major
undergoing major abdominal surgery indicated? abdominal operations such as gastrectomy,
gastric bypass, and splenectomy.
When? At the same time as the major procedure B -
How? By the same route of access as the major B -
procedure
Symptomatic gallstones without Is surgery Yes B -
complications indicated?
When? Elective surgery is acceptable B -
How? Laparoscopic and small-incision A -
cholecystectomies are preferable
to open cholecystectomy
Acute cholecystitis Is surgery Yes B -
indicated?
When? Within 1 week of onset of symptoms A -
How? Laparoscopic cholecystectomy A -
Pancreatitis Is surgery Yes A -
indicated?
When? In the same hospital admission for B -
mild pancreatitis
As soon as the general condition B -
improves and pancreatic necrosis
becomes sterile in severe pancreatitis
How? Laparoscopic cholecystectomy B -
Obstructive jaundice Is surgery Yes A
indicated?
When? Obstructive jaundice needs to be B
treated immediately
How? Laparoscopic cholecystectomy with B
laparoscopic bile duct exploration
or laparoscopic cholecystectomy with
intraoperative endoscopic
sphincterotomy if expertise and
infrastructure are available. If
these are not available, laparoscopic
cholecystectomy in combination with
preoperative or postoperative ERCP is
a suitable alternative.
High-risk patients with temporary Is surgery Yes A Temporary percutaneous cholecystostomy
237
238 Gurusamy & Davidson
safety of anesthesia during early pregnancy, however, has not been established.95 So,
it is best to avoid surgery during the first trimester of pregnancy if possible. Another
issue of laparoscopic surgery in pregnant women is to gain access without causing
injury to the enlarged uterus, particularly in the third trimester. Because of this, a signif-
icant proportion of the operations may have to be performed by open cholecystec-
tomy. Thus, the second trimester appears to be the best time for performing
cholecystectomy in pregnant women (grade B).
In the study including 9714 pregnant women who underwent cholecystectomy,
patients who underwent laparoscopic cholecystectomy had lower surgical morbidity,
fewer maternal complications (hysterectomy, caesarean section, and dilation, and
curettage), fewer fetal complications (fetal death, loss, or distress), and shorter
hospital stay compared with those who underwent open cholecystectomy.90 There
is likely to be a selection bias favoring laparoscopic cholecystectomy however, as
surgeons are more likely to opt for the open approach in the presence of complica-
tions such as severe inflammation or empyema, particularly if this is during the third
trimester. Other studies have shown that laparoscopic cholecystectomy can be
done safely with similar morbidity as open cholecystectomy during pregnancy.96,97
The overall surgery-related morbidity and hospital stay were higher in the pregnant
women undergoing cholecystectomy as compared with nonpregnant women under-
going cholecystectomy.90 Both maternal and fetal outcomes should be considered
in relation to the management of gallstones during pregnancy and further studies
are required on the risks and benefits of cholecystectomy.
With certain reservations about obtaining access in the third trimester and the safety
of anesthesia and pneumoperitoneum in the first trimester, laparoscopic cholecystec-
tomy appears to be the preferred route for cholecystectomy in pregnant women in the
second trimester of pregnancy (grade B).
SUMMARY
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