Asymptomatic Cholelithiasis: Is Cholecystectomy Really Needed?
A Critical Reappraisal 15 Years After the Introduction
of Laparoscopic Cholecystectomy
George H. Sakorafas · Dimitrios Milingos ·
George Peros
Received: 13 December 2005 / Accepted: 12 January 2006 / Published online: 28 March 2007
C
Springer Science+Business Media, Inc. 2007
Abstract Asymptomatic cholelithiasis is increasingly
diagnosed today, mainly as a result of the widespread use of
abdominal ultrasonography for the evaluation of patients for
unrelated or vague abdominal complaints. About 10–20%
of people in most western countries have gallstones, and
among them 50–70% are asymptomatic at the time of
diagnosis. Asymptomatic gallstone disease has a benign
natural course; the progression of asymptomatic to symptomatic
disease is relatively low, ranging from 10–25%.
The majority of patients rarely develop gallstone-related
complications without first having at least one episode of
biliary pain (“colic”). In the prelaparoscopy era, (open)
cholecystectomy was generally performed for symptomatic
disease. The minimally invasive laparoscopic cholecystectomy
refueled the discussion about the optimal management
of asymptomatic cholelithiasis. Despite some controversy,
most authors agree that the vast majority of subjects should
be managed by observation alone (expectant management).
Selective cholecystectomy is indicated in defined subgroups
of subjects, with an increased risk for the development of
gallstone-related symptoms and complications.Concomitant
cholecystectomy is a reasonable option for good-risk patients
with asymptomatic cholelithiasis undergoing abdominal
surgery for unrelated conditions. Routine cholecystectomy
for all subjects with silent gallstones is a too aggressive
management option, not indicated for most subjects with
asymptomatic cholelithiasis. An in-depth knowledge of the
natural history of gallstone disease is required to select the
optimal management option for the individual subject with
G. H. Sakorafas ( ) · D. Milingos · G. Peros
4th Department of Surgery, Athens University, Medical School,
“ATTIKON” University Hospital, Arkadias 19–21,
GR-115 26 Athens, Greece
e-mail: georgesakorafas@yahoo.com
silent gallstones.Management options should be extensively
discussed with the patient; he or she should be actively
involved in the process of therapeutic decision making.
Keywords Silent gallstones . Laparoscopic
cholecystectomy . Porcelain gallbladder . Incidental
cholecystectomy . Concomitant cholecystectomy .
Gallbladder carcinoma . Cancer
Introduction
Cholelithiasis constitutes one of the most common causes
of hospitalization due to gastrointestinal problems in
developed countries and accounts for an important part of
health care expenditure. It shows a worldwide distribution
and a high incidence. especially among particular nations
and geographic areas in the world. The definite treatment
of choice for gallstone disease is cholecystectomy. Until the
introduction of laparoscopy, surgery (open cholecystectomy)
was generally indicated only for patients with symptomatic
and complicated disease [1, 2]. However the establishment
of laparoscopic cholecystectomy as the gold standard for the
treatment of cholelithiasis has created new interest for the
management of patients with silent gallstones. As a minimally
invasive technique, with many well-known advantages
over open cholecystectomy, laparoscopic cholecystectomy
renewed the interest and fueled the discussion regarding the
optimal management of asymptomatic gallstone disease.
Today, asymptomatic cholelithiasis is a very common
clinical entity; the surgeon sees an increasing number of
such subjects, owing to the widespread availability and
use of abdominal ultrasonography for the investigation
of a variety of abdominal diseases or vague abdominal
complaints and in cases of routine checkup. Management of such incidentally discovered gallstones poses a real dilemma
for both the physician and the patient; conclusive evidence
of benefits of cholecystectomy is lacking [3].
The aim of the present study was to critically discuss and
summarize currently available data regarding optimal management
of asymptomatic patients, taking into account the
natural history of asymptomatic cholelithiasis, the potential
for the development of complicated gallstone disease, and
the potential morbidity and mortality of cholecystectomy.
Asymptomatic cholelithiasis: the extent
of the problem
When discussing asymptomatic cholelithiasis, the first priority
is to define this entity. Asymptomatic cholelithiasis exists
when gallstones are detected in the absence of gallstonerelated
symptoms, such as history of biliary pain (pain in the
epigastrium or right upper abdominal quadrant that may radiate
to the patient’s back or to the right scapula), or gallstonerelated
complications such as acute cholecystitis, cholangitis,
or pancreatitis (Rome Group for the Epidemiology and Prevention
of Cholelithiasis [GREPCO]) [4]. Other nonspecific
symptoms or vague dyspeptic problems, such as epigastric
discomfort, dyspepsia, flatulence, nausea, abdominal gurgling
noises, or pain outside the right hypochodrium, cannot
be considered as symptomatic cholelithiasis and could easily
be attributed to other gastrointestinal diseases (such as peptic
ulcer disease, irritable bowel syndrome) [5, 6]. Therefore,
and when discussing surgery under this situation, the patient
should understand that these symptoms may persist following
cholecystectomy. However, the fact that patientswith that
kind of nonspecific symptomatology may sometimes benefit
from cholecystectomy could indicate that cholelithiasis
contributes, at least to some extent, to that vague clinical
picture (see Selective Cholecystectomy—Vague Dyspeptic
Symptoms) [7].
In 1992, it was estimated that 10–15% of the adult population
in the USA had gallstones (which amounted to more
than 20 million people),withwomen suffering twice asmuch
as men [4, 5, 8–10]. About one million patients are newly diagnosed
annually (10) and among them 50–70% are asymptomatic
at diagnosis (6, 8). Approximately 600,000 patients
underwent cholecystectomy in 1991 in the USA [11] and
about 4–7% of those operated had asymptomatic cholelithiasis
[12]. The annual cost for the treatment of those patients
had been estimated to be around $5 billion (estimates from
1993) [10].
Similar results have been reported in Europe. The Rome
Group for the Epidemiology and Prevention of Cholelithiasis
found gallstones in 8% of Roman male civil servants
between the age of 20 and 69 years. Fewer than 8% had
a history of symptoms compatible with biliary colic [13,
14]. The same group found a prevalence of as high as 25%
in female civil servants in the 60- to 64-year age group
[13, 14]. One third reported at least one episode of biliary
pain over a period of 5 years [4]. In the Italian Multicenter
Italian Study on Cholelithiasis, 29,739 participants were
examined by ultrasound and questionnaire with respect to
the presence of gallstones and related symptoms [15]. The
prevalence of gallstones for women was 10.5% and for men
6.5%. This increased to 18.9% and 9.5%, respectively, when
subjects who had already undergone cholecystectomy were
added. A linear increase in prevalence was noted with age in
both genders. The vast majority of subjects with gallstones
were asymptomatic (84.9% of women and 87% of men).
Similar numbers were found in a Scandinavian study, where
the overall prevalence of gallstones was 15%, with women
having a higher prevalence both at 40 and at 60 years of age
as compared with men (11% and 25% versus 4% and 15%,
respectively) [16]. In the United Kingdom, around 5,500,000
people have gallstones and more than 50,000 cholecystectomies
are performed each year [17].
It therefore appears that the overall prevalence of gallstone
disease in industrialized countries is between 10% and 20%.
The prevalence rises with age in both genders (close to 10
per 1,000 subjects per year) [18]. At the age of 65, about
30% of women have gallstones, and by the age of 80, 60%
of both men and women have them [19]. These data confirm
the high prevalence of gallstone disease and also shows that
most patients are unaware of it.
Natural history of asymptomatic gallstones
There is no innocent gallstone
—William J. Mayo, MD, 1904
It is unfortunate that so few appreciate from what small
causes diseases come.
—Charles H. Mayo, MD, 1902
About 100 years after the above-noted Mayo dictum about
gallstones, there is now enough evidence that most incidentally
discovered, clinically silent gallstones rarely have
clinical significance [3, 20–24]. In most Western countries,
the majority of patients with asymptomatic cholelithiasis
remain asymptomatic throughout their life, and do not require
any treatment [25]; in fact, these subjects live and
die with their gallstones having never caused pain or other
medical problems. Autopsy studies showed that more than
90% of autopsied patients with gallstone disease died from
unrelated causes. Death as the ultimate complication from
asymptomatic gallstones is very rare (∼3–7% of deaths),
usually in the elderly as a consequence of biliary or postoperative
complications [26–28].
According to the 1992 NIH Consensus Conference report
[10], 10% of patients develop symptoms during the first 5
years after diagnosis and 20% by 20 years. Similar findings
were reported by Zubler et al. [29], who found that only 10-
18% of asymptomatic patients ever become symptomatic;
the annual risk for developing biliary pain (misnamed as
biliary colic) is 1–4% [17, 30] (Table 1). One could extrapolate
that after 20 years, approximately two thirds of patients
will remain symptom free [25]. These rates are in sharp
contrast with those in symptomatic cholelithiasis, where the
annual rates of developing complications and biliary pain
are 1.2% and 50%, respectively [17]. According to the Italian
GREPCO study, the annual complication rate of initially
asymptomatic patients is 0.3–1.2% [31]. In this study, 151
subjects identified to have gallstones during the GREPCO–
1984 study [4] were followed over a period of 10 years. At
the beginning of the study, 118 patients were asymptomatic.
The cumulative probability of developing complications after
10 years was 3% in the initially asymptomatic group and
7% in the symptomatic group.
In the significant study by Gracie and Ransohoff [32],
123 Michigan University faculty members (110 men and 13
women) found to have gallstones through routine screening
were followed for 15 years. At 5, 10, and 15 years of followup,
10%, 15%, and 18%, respectively, became symptomatic.
The approximate rate at which the subjects developed biliary
pain was 2% per year for the first 5 years without a
subsequent decrease over time. Three patients in this study
developed biliary complications, all of which were preceded
by biliary colic. Based on these results, the authors concluded
that prophylactic cholecystectomy for asymptomatic
cholelithiasis is not justified.
A longitudinal follow-up study of asymptomatic gallstones
showed that over a 20-year period only18%of patients
developed biliary pain and that the mean yearly probability
of the development of biliary pain is 2% during the first
5 years, 1% during the second 5 years, 0.5% during the third
5 years, and 0% during the fourth 5 years. None of these
individuals died because of gallstone disease [33].
According to Hermann [34], 40–60% of persons with
cholelithiasis remain asymptomatic, 60–70% present with
mild symptoms of chronic cholecystitis (among them, 20%
have manifestations that are difficult to interpret), 20% develop
acute cholecystitis, and 10% develop complicated
acute cholecystitis (i.e., cholecystitis accompanied by jaundice,
cholangitis, or pancreatitis). Hermann concluded that
the longer patients live with gallstones, the more likely they
are to experience pain or complications [34].
In Japan, Wada and Imamura [35] found that 20% of patients
with asymptomatic cholelithiasis turned symptomatic
after a median follow-up of 13 years. Patients over the age
of 70 were more likely to become symptomatic than patients
under 70. McSherry et al. [36] followed 135 asymptomatic
men and women with gallstones who were subscribers to the
Health Insurance Plan of Greater New York. Ten percent developed
symptoms and only 7% required cholecystectomy
over a median follow-up of 46.3 months. Cucchiaro et al.
[37] followed 125 asymptomatic patients for a period of
5 years. Fifteen patients developed symptoms during that
time and two underwent emergency surgery for gallstone
complications. Fifty-four patients died during that period
because of unrelated causes (malignancies, cardiovascular
disease, renal insufficiency).
Friedman et al. [38] observed 123 asymptomatic patients
over 25 years in a prepaid health plan; serious or mild events
(acute cholecystitis, acute biliary pancreatitis, obstructive
jaundice) occurred in 4% of these asymptomatic patients.
Wacha and Ungeheuer in their review [39] reported higher
rates of conversion from asymptomatic to symptomatic state;
according to these authors, as many as 50% of individuals
with asymptomatic gallstones will be operated on or develop
symptoms within 10–20 years after the initial diagnosis.
Aging is found to be associated with the development of
symptoms or complications, and in particular if the followup
is long enough, in an increasing percentage of patients,
up to 30–50% [34, 36, 40, 41]. The incidence of choledocholithiasis
at the time of cholecystectomy is directly related
to age (9% in those 31–40 years old to 96% in those 80–90 years old) [5]. As is well known, choledocholithiasis
may be associated with potentially serious complications,
such as acute cholangitis and/or pancreatitis. This is of particular
practical importance for the patient and the physician,
because patients with advanced age exhibit higher morbidity
and mortality rates, whereas themanagement of complicated
gallstone disease may require more complicated procedures
than simple laparoscopic cholecystectomy. However, this issue
remains controversial; other authors observed that the
probability of developing symptoms and/or complications
fell steadily over time [10, 25, 31–33]; according to these investigators,
the longer patients were asymptomatic, the less
likely they were to develop symptoms.
In summary,most studies (conducted mainly in the 1980s)
indicate that the progression of asymptomatic to symptomatic
disease is relatively low, ranging from 10–25% [42–
45]. The major concern when discussing the natural history
of asymptomatic cholelithiasis is the possible development
of a severe, potentially life-threatening complication, such as
severe (necrotizing) pancreatitis or acute suppurative cholangitis.
Existing data show, however, that the majority of patients
rarely develop complications without first having at
least one episode of biliary colic pain [5, 10, 17, 32, 36];
biliary colic usually occurs within the first 5 years of the initial
diagnosis [20]. From a practical point of view, it would
be very important for both the patient and the physician if
we could recognize the subgroup of asymptomatic patients
who will become symptomatic. Unfortunately, it is impossible,
using local (such as number, size, nature, alteration in
wall thickness or gallbladder contractility) or general factors
(such as age, gender, associated comorbidities) to predict
who—among asymptomatic patients—will ever develop
symptoms or complications and when [3]. Some authors tried
to classify asymptomatic patients into two groups: a low-risk
group and a high-risk group. The low-risk patients are those
with a functioning gallbladder whose calculi are >3 mm
but <2 cm in diameter and radiolucent, and who are free
of concomitant serious disease [5]. The high-risk patients
are those more likely to develop acute cholecystitis, acute
pancreatitis, or other complications of cholelithiasis and include
those with large stones (>2.5 cm) and those with small
multiple calculi (microlithiasis, stones <3 mm in diameter),
biliary sludge, or both, who tend to develop acute cholangitis
or pancreatitis [46–48]. The risk of complicated cholelithiasis
is admittedly higher when the cystic duct is chronically
obliterated [5].
Management of asymptomatic cholelithiasis
Treatment options for asymptomatic cholelithiasis include
expectant management (observation alone) and cholecystectomy
(laparoscopic), which can be performed either selectively
(for selected subgroups of patients with asymptomatic
cholelithiasis), routinely (for all patients with asymptomatic
cholelithiasis), or concomitantly during another intraabdominal
operation for an unrelated pathologic condition (e.g.,
cancer of the colon).
Expectant management (observation alone)
Because the majority of patients with asymptomatic
cholelithiasis remain asymptomatic throughout their life,
most authors agree that expectant management (watchful
waiting) is the most reasonable treatment for the majority of
these patients [3, 17, 20–23, 49–51). This approach avoids
overtreatment (an unnecessary surgical procedure under general
anesthesia) in the vast majority of asymptomatic patients
who will never develop symptoms. The disadvantage of this
approach is that no one can guarantee the patient that he
or she will never suffer a potentially severe or even lethal
complication of gallstone disease, such as gallbladder cancer
or severe acute pancreatitis, usually at a more advanced
age (Table 2). In this case, emergency surgery for a serious
complication of cholelithiasis may be needed at a later date.
Moreover, in such a setting, the operation ismuch more complicated
and it is performed more frequently by laparotomy,
which may increase morbidity and mortality, especially in
older patients with comorbidities [5]. However, the patient
should recognize that this theoretical possibility is rare. Usually
the conversion from the asymptomatic to symptomatic
state happens by the occurrence of a biliary colic, thereby
indicating the need for surgery in the—then symptomatic—
patient. In conclusion, and considering that the vast majority
of asymptomatic patients remain asymptomatic throughout
their life and that most asymptomatic patients develop symptoms
before the occurrence of complications, prophylactic
surgical therapy is not justified—with a few exceptions (see
Selective Cholecystectomy). According to the NIH Consensus
Conference report [10] “the availability of laparoscopic
cholecystectomy should not expand the indications for gallbladder
removal.”
Surgical management (cholecystectomy)
Currently, laparoscopic cholecystectomy is the gold standard
in the management of cholelithiasis, given the safety
and ease of performance and the many well-known advantages
of this approach over the conventional open cholecystectomy,
including short hospital stay, lesser need for
postoperative analgesia, better cosmetic results, fast recovery
to full preoperative activity, and avoidance of long-term
complications (i.e., incisional hernia) [52, 53]. Conversion to
open cholecystectomy may be required for a small percentage
of patients when the laparoscopic approach is associated
with operative difficulties or when the operating surgeon feels at surgery that laparoscopic cholecystectomy cannot be
performed safely for a variety of reasons (e.g., presence of
firm adhesions owing to previous abdominal operations, difficulty
in identifying vital anatomical structures, etc). About
15 years after its introduction, laparoscopic cholecystectomy
is considered to be a safe operation, with low morbidity and
overall mortality ranging from 0.14–0.50% in different studies,
depending on the age and fitness of the patients [54].
However, despite the fact that morbidity has decreased as the
years go by, as more operative experience is gained, and experienced
in laparoscopy surgeons are involved in the training
of the new generation of surgeons [55], complications—
potentially severe—do exist and should not be neglected
(Table 3).
Routine cholecystectomy
As discussed previously, most authors agree that routine
cholecystectomy is not indicated for asymptomatic cholelithiasis. Some, however, maintain that all asymptomatic
patients should routinely be operated. The main argument
is that surgery can be performed much more safely
before the development of potentially serious or even fatal
complications (such as acute cholecystitis, cholangitis, pancreatitis),
something that usually occurs at a more advanced
age and may demand urgent surgery in older patients, with
higher morbidity and mortality [5, 40–43, 56]. In contrast,
in young, low-risk patients, laparoscopic cholecystectomy
is an almost innocuous procedure with low morbidity and
practically no mortality [5]. According to this surgical philosophy,
precluding or postponing laparoscopic cholecystectomy
may be more risky than undertaking an elective operation
[5]. Even in the prelaparoscopic cholecystectomy era,
Glenn stated that “It is reasonable to strongly recommend
an early (open) cholecystectomy for gallstones, whether or
not they cause symptoms, unless there is a contraindication
to operation. The optimum treatment for asymptomatic
cholelithiasis is elective cholecystectomy without undue
delay” [40, 41]. Laparoscopic cholecystectomy is easier in
asymptomatic than in symptomatic patients, with lesser operative
time (92.1 versus 106 minutes), lower conversion rate
to open cholecystectomy (1.57% versus 4.6%), and lesser
morbidity (4.72% versus 8.80%) (p < 0.05) [57]. Although
mortality after laparoscopic cholecystectomy is 0.6% for all
age groups, it increases with aging, mainly because of the
presence of significant comorbidities in older patients (0.14–
0.4% in patients <50 years, and 4.5% in those >65 years)
[19, 58]. Operative mortality also increases after a “difficult”
cholecystectomy (defined as an operation performed
after a biliary complication, usually acute cholecystitis or
choledocholithiasis, has occurred, even if the acute event has
subsided) compared to a “simple” cholecystectomy (prophylactic
cholecystectomy or cholecystectomy after an episode of uncomplicated biliary pain) (mortality, 0.4% for patients
with chronic cholecystitis, 1.2% for those with acute cholecystitis,
1.2–1.6% after choledochotomy and common bile
duct exploration) [5, 32, 58]. Interestingly, in the study by
Morgenstern et al. [59] all the deaths after cholecystectomy
occurred in patients older than 66 years (mean age, 80.5
years). These authors confirmed also that the mortality increased
threefold when choledochotomy become necessary
[59]. Table 4 summarizes the advantages and disadvantages
of elective (routine) cholecystectomy in patientswith asymptomatic
cholelithiasis.
Selective cholecystectomy
Laparoscopic cholecystectomy can be performed in selected
subgroups of patients with asymptomatic cholelithiasis, who
are at greater risk for the development of symptoms or complications
(Table 5) [5, 11, 50–52, 60].
Chronic hemolytic syndromes
Patients suffering from chronic hemolytic syndromes (such
as sickle cell disease [SCD]) are at risk for gallstone development
at a young age (as a result of repeated hemolytic
crises). Pigment gallstones are reported in 58% of patients
with homozygous SCD and in 17% of patients with heterozygous
types of hemoglobinopathies [61, 62]. Two thirds
of patients with gallstones have symptoms, although it is
often difficult to distinguish between a sickle cell crisis and
acute cholecystitis [63]. Patients with other hemolytic anemias
are also at risk for gallstone development and many
will become symptomatic [64]. Laparoscopic cholecystectomy
should be considered for asymptomatic patients with
chronic hemolytic syndromes for many reasons [65, 66]:
Biliary complications of gallstone disease and vasoocclussive
crisis both present with similar manifestations (nausea, abdominal pain, fever, leukocytosis, and
cholestatic jaundice) and therefore differential diagnosis
may be difficult.
The onset of gallstones at a young age in SCD raises
the lifetime risk of biliary complications, and therefore,
cholecystectomy following the diagnosis of asymptomatic
gallstones in patients with SCD is advisable and justified.
Interestingly, the approach of elective cholecystectomy
for asymptomatic cholelithiasis in SCD patients was not
generally accepted until recently; in the past, surgery in SCD
was associated with a high morbidity and mortality owing
to vaso-occlusive crises [61, 67]. However, with the introduction
of laparoscopic cholecystectomy, the establishment
of its safety in patients with SCD and cholelithiasis, and
the significant improvement of anesthetic techniques, more
patients (adults and children) are being referred for laparoscopic
cholecystectomy [68, 69]. Pediatricians have started
screening their patients for gallstones and referring them
for laparoscopic cholecystectomy before the development
of symptoms and/or complications of the disease [70]. Reduction
of Hb-S to a level lower than 50% by preoperative
partial exchange transfusion is believed to be associated with
a lower risk of veno-occlusive crises [61, 71]. Avoiding open
cholecystectomy during acute crises or acute cholecystitis
has been advocated [65]. In the laparoscopic era, although
surgery should be avoided during veno-occlusive crises, laparoscopic
cholecystectomy for acute cholecystitis is not a
contraindication provided that all the precautions to guard
against a veno-occlusive crisis are taken [3].
Transplantation
Prophylactic cholecystectomy should be strongly considered
for patientswith asymptomatic gallstoneswaiting to undergo
solid organ transplantation [72, 73]. Prophylactic cholecystectomy
can be performed either during the pretransplant
period or—when appropriate—at the time of transplantation.
The theoretical basis for this recommendation is that
these patients are more likely to become symptomatic, especially
in the first 2 years after transplantation [73].Moreover,
because of immunosuppression, diagnosis of complications
of cholelithiasis may be more difficult; these complications
are associated with increased morbidity and mortality. The
aim of prophylactic cholecystectomy is to remove of a possible
septic focus that carries a high potential for severe
complications in immunosuppressed patients [72, 73]. The
mortality rate associated with emergency cholecystectomy
in patients who have received a heart transplant is high,
up to 36% in the review by Begos et al. [74]. Finally, cyclosporine
and tacrolimus (FK 506), used as immunosuppressive
agents, are prolithogenic because of decreased bile
salt export pump function [19]. Episodes of acute cholecystitis
during episodes of maximum immunosuppression or
during rejection episodes have been reported.
Not all authors, however, concur with this aggressive surgical
philosophy in transplant patients [75–79]. Greenstein
et al. [76] follow 21 renal transplant patients with silent
gallstones for 4 years. Thirteen patients (87%) remained
asymptomatic, and 3 patients (1 had diabetes) developed
acute cholecystitis and underwent laparoscopic cholecystectomy
with no complications. Similarly, Courcoulas
et al. [79] followed up 26 transplant patients (including
renal, heart, double lung, and heart–lung recipients) who
underwent laparoscopic cholecystectomy; 73% of these
patients had symptomatic gallstones. These authors found
that laparoscopic cholecystectomy is as safe in the transplant
population as in the general population and the advantages of
short hospital stay, low morbidity and early return to preoperative
routines remain equivalent. Melvin et al. [78] found
that in renal transplant patients, when surgery for gallstones
is needed, it was associated with a low risk and does not
represent an increased rate of complications in renal transplant
patients with 1-, 2-, and 5-year graft survival or 98%,
96%, and 80%, respectively. According to these authors,
expectant policy should be exercised in transplant patients
with silent gallstones. Once gallstones become symptomatic,
laparoscopic cholecystectomy can be safely performed
with no adverse effect on morbidity, mortality or graft
survival.
Gallbladder carcinoma
Gallbladder cancer, although rare in most Caucasian populations,
is amongst the most frequently observed cancers
in native populations of North and South America, and in
the Maori population of New Zealand, possibly as a result
of early onset of gallstones [80–83]. The increased incidence
of gallstones (at an early age) in these ethnic groups
may be due to the presence of cholesterol lithogenic genes
that are highly prevalent in these populations [83]. North
American Indianwomen develop gallbladder carcinomawith
a greater frequency than heavy smokers develop pulmonary
cancer [5, 84]. In all populations, there is a strong correlation
between gallstones and gallbladder cancer. The risk
of gallbladder cancer is approximately four times higher in
cases with than in those without gallstones. It is estimated
that about 80% of patients developing gallbladder carcinoma
have gallstones, especially large stones (≥3 cm) [27]. The
risk of underlying malignancy is also high in patients with
gallbladder polyps larger than 10 mm in diameter [81, 85–
87]. Calcified or porcelain gallbladder is associated with
carcinoma in 13–25% of patients [8, 88–90]. Recently, some
authors questioned the association of porcelain gallbladder
with gallbladder carcinoma [91, 92]. According to these authors,
a calcified gallbladder is indeed associated with an increased risk of gallbladder cancer, but at a much lower
rate than previously estimated [91]. Interestingly, Stephen
et al. [91] found that the incidence of cancer depends on
the pattern of calcification, with selective mucosal calcification
being associated with a greater risk compared to diffuse
intramural calcification.
When examining the role of cholecystectomy as a therapeutic
strategy to prevent the development of gallbladder
carcinoma, the surgeon and the patient should acknowledge
that—despite the association of gallstones with gallbladder
carcinoma—the risk of developing cancer in all patients
with asymptomatic gallstones is less than 0.01%, less than
the mortality associated with cholecystectomy [12, 17].
Therefore, prophylactic cholecystectomy is not indicated
for the general population with asymptomatic cholelithiasis
to prevent future gallbladder cancer [12, 17, 27, 64, 93,
94]. Nevertheless, based on the above data, prophylactic
cholecystectomy to prevent gallbladder carcinoma should
be strongly considered in selected subgroups of patients
with silent gallstones, such as in patients of some ethnic
groups living in areas where gallbladder carcinoma is
prevalent (American Indians and Mexican Americans,
Colombia, Chile, Bolivia) [33, 80–83, 95, 96]. Indications
for cholecystectomy should be liberalized in these high-risk
populations [5]. The increasing frequency of laparoscopic
cholecystectomy in these geographic areas, and the lower
threshold for referral, probably will lower the incidence and
mortality rates for this lethal disease [81, 97]. Moreover,
prophylactic cholecystectomy is indicated in patients with
gallbladder polyps larger than 10 mm in diameter and in patients
with large gallstones (>3 cm) (see above) [27, 33, 81,
85–87, 97] (Table 5). Finally, and despite some controversy
[91, 92], most authors recommend selective prophylactic
cholecystectomy for patients with porcelain gallbladder to
prevent the development of gallbladder carcinoma [8, 11, 12,
88–90].
Diabetes mellitus
Prophylactic cholecystectomy has been recommended for
diabetic patients with silent gallstones [5]. This approach
has been based on the belief that diabetic patients belong to
the high-risk group for the development of complications of
gallstone disease (such as infected bile, gangrenous changes
and perforation of the gallbladder), that are more severe than
in the general population [98, 99]. Earlier reports found that
the risk of acute cholecystitis and subsequent perioperative
morbidity and mortality was significantly higher in diabetic
compared to nondiabetic patients [5, 100, 101]. It is believed
that the autonomic neuropathy in diabeticsmay mask the pain
and other clinical signs associated with acute cholecystitis
[102], thereby delaying accurate diagnosis and appropriate
management. Therefore, in the past surgeons were urged to
consider a diabetic as a high-risk group and prophylactic
cholecystectomy was recommended [5, 94, 100].
Recent evidence, however, has shown that the natural history
of gallstones in diabetics is generally more benign than
thought in the past, with a low risk of a major complications
[103]. The cumulative percentage of initially asymptomatic
non–insulin-dependent diabetic patients who presented with
symptoms and complications was small (14.9% and 4.2%,
respectively) [103]. Also, diabetes as an independent risk
factor for the formation of gallstones has been questioned
[104] and the prevalence of gallstones was found to be similar
among diabetic patients (14.4%) and control subjects
(12.5%), in a case-control analysis [105, 106]. Moreover,
the rates of operative morbidity and mortality for biliary
surgery in diabetics currently are comparable, with rates
in nondiabetics once other comorbidities such as cardiovascular
and renal disease are taken into consideration [98,
107–109]. Therefore, there is no clear benefit to prophylactic
cholecystectomy in diabetic patients with asymptomatic
gallstones, because surgery does not appear to increase either
the duration or quality of life, but may in fact reduce
it [11, 32, 98, 103, 107, 109–111]. Consequently, diabetic
patients should be managed expectantly with the same criteria
as the general population [3, 98, 110, 112]. However,
early elective cholecystectomy is advocated once symptoms
develop [105].
Vague dyspeptic symptoms
Although patients with gallstones who complain of nonspecific
dyspeptic symptoms (such as vague abdominal pain,
bloating, fullness, and/or belching) without biliary colic are
less likely to improve following cholecystectomy, a large
percentage (up to 70%) of them still benefit from surgery
[6, 113]. This suggests that indeed these vague, dyspeptic
symptoms may be caused by gallstones; therefore, laparoscopic
cholecystectomy is expected to improve significantly
the quality of life in patients with asymptomatic
cholelithiasis who reported vague symptoms [6]. An important
practical question, however, is if these patients are truly
“asymptomatic” and if gallstones are really “silent.”
Other indications for selective cholecystectomy
in asymptomatic cholelithiasis
Asymptomatic cholelithiasis in association with stones in
the common bile duct is another indication for selective prophylactic
surgery, because the presence of ductal stones predispose
to potentially severe complications in a significant
percentage of patients (up to 50%) [114, 115].
Selective cholecystectomy should also be considered for
patients with silent gallstones living in a part of the world
very remote from medical facilities. These patients may be at risk for an adverse outcome should a complication of
gallstone disease develop.
Incidental, concomitant cholecystectomy
for asymptomatic cholelithiasis during another
abdominal operation
Concomitant cholecystectomy for asymptomatic cholelithiasis
(diagnosed either preoperatively or intraoperatively) during
a planned abdominal operation is a common clinical
scenario. Several studies showed a high (up to 70%) incidence
of symptoms and/or complications from the biliary
system (such as biliary colic, acute cholecystitis, jaundice)
in patients with asymptomatic cholelithiasis following laparotomy
for unrelated conditions; cholecystectomy was required
in a large percentage (up to 40%) of these patients
within 1 year of the initial operation [116–121]. The aim of
incidental cholecystectomy in this case is to prevent postoperative
cholecystitis or the later development of symptoms.
Of course the addition of cholecystectomy should not
add risks to the patient. In most patients, cholecystectomy
“en passant” can be performed safely [119, 121]; therefore,
concomitant cholecystectomy during another intraabdominal
procedure is a reasonable option for the vast majority of
patients [116, 121], unless specific contraindications exist.
Ideally, gallstones should be detected preoperatively by ultrasonography;
this allows the discussion with the patient before
surgery to obtain his or her consent for cholecystectomy. The
discussion should emphasize the safety and purpose of the
procedure and not dismiss the possible complications, albeit
rare, as with any additional surgical procedure. In addition,
preoperative diagnosis of silent gallstone disease allows a
better planning of the incision [121].
Cholecystectomy-related complications can be avoided
by using the proper surgical technique, including proper exposure,
by performing an uncomplicated primary operation,
and by proper patient selection taking into account comorbidities
and general health [122]. Obviously, this strategy
is not recommended for high-risk patients, with significant
comorbidities, where a minimal operating and anesthesia
time is required for an uneventful recovery. Clinical judgment
at the time of surgery and caution are required from
the part of surgeon to select the optimal management option
for the individual patient. Local conditions (eg, presence
of a shrunken or scarred gallbladder, cirrhosis, extensive
firm adhesions, and/or tissue scarring) should be taken
into consideration. Incidental cholecystectomy for asymptomatic
cholelithiasis is contraindicated when a prosthetic
material (such as vascular graft, mesh for incisional hernia
repair) is used during surgery [123]. The performance
of concomitant cholecystectomy may be more difficult in
the case of a pelvic (gynecologic) procedure, because it
may require an additional or extended incision. However,
this poses no problem if the pelvic procedure is conducted
laparoscopically [3].
Comments
Laparoscopy not only simplified the treatment of cholelithiasis,
because of the many and clear advantages of the minimally
invasive approach compared to the open method, but
also resulted in a broadening of the indications of cholecystectomy
and in a decrease of “the surgical threshold”
for the surgical management of patients with asymptomatic
cholelithiasis. This caused a worldwide increase of the number
of cholecystectomies by 18.7% between 1989 and 1993,
with an increase of 25% in the age group of 45–64 years
[17, 99, 124–125]. This may reflect a change in surgeons’
attitude toward some of the indications for cholecystectomy,
including asymptomatic gallstones [99, 124]. Surgeons may
be treating asymptomatic gallstone disease or resorting to
laparoscopic cholecystectomy as a “diagnostic therapeutic
test” [127]. This liberal surgical attitude has been further
promoted by a lower referral threshold by general practitioners
and gastroenterologists asking for surgical treatment
by laparoscopic cholecystectomy, as a result of the enhanced
perceived benefits of laparoscopic cholecystectomy. These
referring physicians often warn patients that they are at an
increased risk for the development of severe and potentially
lethal complications, causing an unnecessary anxiety to them
and suggesting surgery despite the lack of sufficient data to
support such an aggressive management approach. Based on
existing evidence, physicians should frame their discussions
with patients in such a manner as to inform them of the relative
risk of an expectant approach versus cholecystectomy,
thereby allaying unfounded fears of the expectant management
approach. Another significant reason for the increase
of the number of (laparoscopic) cholecystectomies is the
increased acceptability and demand of minimally invasive
surgery by patients, so that few patients refuse surgical treatment,
especially after the diagnosis of a “potentially lethal”
disease is discussed with the referring physician [124].
Minilaparotomy (open) cholecystectomy is another alternative,
but worldwide most surgeons (and patients) prefer
the laparoscopic approach. Unfortunately, often both the referring
physician and the patient do not take into account
the natural history of asymptomatic cholelithiasis and the
operation/anesthesia-related potential morbidity and mortality.
The end result is the unnecessary overtreatment of a
large percentage of subjects with asymptomatic cholelithiasis
and the very long lists of patients waiting to undergo
cholecystectomy [52]. Among these, of course, are included
patients who are symptomatic and who have absolute indication
for surgery; the long waiting lists may delay surgery
for these symptomatic patients with potential adverse effects (development of complications, higher conversion rates to
open cholecystectomy, increased morbidity/mortality, prolonged
hospitalization, etc) [128, 129]. The increased cost
and workload for the health system, because of a costly and
unnecessary operation not indicated for most patients with
asymptomatic cholelithiasis, is another factor that should be
taken into consideration when discussing such a controversial
issue [130]. Given the high prevalence of gallstones, the
cost of prophylactic cholecystectomy is almost four times
that of expectant management. It has been estimated that the
average cost in Britain is about 5.89 million euros/10,000
patients with asymptomatic cholelithiasis [30]. Considering
these numbers and the limited financial resources in health
care, and taking into account the natural history of asymptomatic
cholelithiasis, it appears unreasonable to treat every
patient diagnosed with silent gallstones with cholecystectomy
[11].
All patients with asymptomatic cholelithiasis should be
fully informed about the natural history of silent gallstone
disease and about management options. Existing data support
a conservative approach for the large majority of patients
with asymptomatic cholelithiasis. Surgery should be
offered to selected subgroup of asymptomatic patients with
gallstone disease (see Table 5). A careful analysis of hepatobiliary
and systemic risk factors (such as advanced age
and significant comorbidity) should precede any decision
regarding cholecystectomy for asymptomatic cholelithiasis.
Patient preferences should be taken into consideration by
the surgeon, because the decision for surgery remains an
individual decision. Patients unwilling to accept the minimal
but real possibility of complications of gallstone disease
may prefer to undergo laparoscopic cholecystectomy, but—
at the same time—they should acknowledge the morbidity
and mortality of the procedure and general anesthesia, albeit
minimal. The surgeon should emphasize to the patient
that the majority of patients with asymptomatic cholelithiasis
rarely develop complications without having at least
one episode of biliary colic. Consequently, laparoscopic
cholecystectomy can be performed as an elective procedure
for the—then symptomatic—cholelithiasis, allowing a
more optimal and reasonable timing for surgery. With modern
surgical and anesthetic techniques, cholecystectomy—
after symptoms develop—results in a mortality rate almost
equivalent to elective cholecystectomy.
In conclusion, the evolution of laparoscopy should not alter
the indications of cholecystectomy. Becausemost asymptomatic
gallstones remain clinically “silent,” routine laparoscopic
cholecystectomy is not indicated for the vast majority
of subjects with asymptomatic cholelithiasis. Laparoscopic
cholecystectomy is a costly procedure performed under general
anesthesia and is associated with the potential of morbidity
(sometimes serious) and mortality. The risks of the
operation outweigh the complications if stones are left in
situ. However, laparoscopic cholecystectomy should be performed
in selected subgroups of patients with asymptomatic
cholelithiasis (see above). Patients should be fully informed
about the natural history and available management options,
their advantages and disadvantages, and be actively involved
in the decision making.
Advantages
Natural history of asymptomatic gallstones is benign
Only 1–4% of patients per year develop symptoms (biliary “colic”)
Only 10 and 20% of patients will develop symptoms 5- and 20-years after the initial diagnosis
Acute biliary symptoms occur in 3%
Almost all patients develop some symptoms (usually biliary colic) before complications arise
Avoidance of a procedure that represents overtreatment for the majority of asymptomatic patients
Avoidance of surgery/anesthesia-related morbidity and mortality
Avoidance of unnecessary cost/workload for the health system
The patient can be operated if and when he or she becomes symptomatic (usually after an episode of biliary colic)
Avoidance of unnecessary surgery/anesthesia in patients with significant comorbidity/advanced age
Disadvantages
Theoretical potential (albeit small) for the development of serious complications of gallstone disease (such as pancreatitis or development of
gallbladder cancer)
About 20% of patients will develop symptoms after 20 years
Compared to elective, emergency surgery is associated with increased morbidity and mortality; mean operating time, mean hospitalization
and conversion (to open cholecystectomy) rates are higher in emergency surgery
Expected management is contraindicated for selected subgroups of patients with asymptomatic cholelithiasis (see Table 5)
Table 3 Complications of laparoscopic cholecystectomy
Common bile duct injury (1%)
Bile leak (3%)
Bleeding (as in open cholecystectomy)
Retained (undetected) stones and/or bile and stone spillage (with the
potential for abscess formation)
Wound infection (1–2%)
Injury to organ/vessels during trocar insertion or during surgery
(very rare)
Complications due to pneumoperitoneum (i.e., gas embolism,
subcutaneous emphysema) (very rare)
General postoperative complications (ie, deep vein thrombosis,
pulmonary embolus, pneumonia, myocardial infarction,
atelectasia—pneumonia, stroke) (as in open cholecystectomy)
TABLA 4
Advantages
Definitive cure of the patient from a disease with a “benign” natural history, but with the potential for
the development of serious and even fatal complications (albeit rare) (including the development of
gallbladder cancer)
Very safe procedure, with low morbidity and virtually no mortality among low-risk patients. Patient’s
problem can be relieved by undergoing a safe operation, which becomes even safer for patients with
asymptomatic cholelithiasis, owing to favorable local conditions (ie, absence of inflammation,
adhesions)
Disadvantages
Overtreatment of a large number of asymptomatic patients who will never develop symptoms or
complications
Potential morbidity and even mortality of surgery/anesthesia
Increased cost/workload for the health system
TABLA 5
Clear indications
Suspicion/risk of malignancy
Gallstones associated with gallbladder polyps >1 cm in diameter
Calcified (porcelain) gallbladder
Some ethnic groups or subjects living in areas with high prevalence of gallbladder cancer associated
with gallstones (American Indians, Mexican Americans; Colombia, Chile, Bolivia, Maori
population of New Zealand)
Presence of large (≥3 cm) gallstones
Asymptomatic cholelithiasis associated with choledocholithiasis
Transplant patients (before or during transplantation)
Chronic hemolytic conditions (sickle cell anemia)
Relative indications
Increased risk of conversion from asymptomatic to symptomatic disease
Life expectancy >20 years
Calculi >2 cm in diameter
Calculi <3 mm and patent cystic duct
Nonfunctioning gallbladder
Diabetes mellitus
Vague dyspeptic symptoms in the presence of gallstones
Questionable indications
Patient living in an area remote from medical facilities
Incidental (concomitant) cholecystectomy during another abdominal operation
