Gallstone diseases in pregnancy - UpToDate

Prévia do material em texto

Gallstone diseases in pregnancy
INTRODUCTION
Gallstones are more common in pregnant compared with nonpregnant patients.
Unlike asymptomatic pregnant patients with gallstones, pregnant patients with
gallstone disease (ie, symptoms related to gallstones) are at an increased risk for
maternal and neonatal morbidity.
As in nonpregnant patients, gallstone disease is classified into uncomplicated (ie,
biliary colic) and complicated (ie, acute cholecystitis, choledocholithiasis,
cholangitis, gallstone pancreatitis) disease. In pregnant patients with biliary colic,
supportive care will often lead to temporary resolution of symptoms, but
symptoms frequently recur later in pregnancy or postpartum. Pregnant patients
with repeated attacks of biliary colic or with complicated gallstone disease will
require an invasive procedure; cholecystectomy is one of the leading
nonobstetrical indications for surgery in pregnant patients, second only to
appendectomy ( table 1).
Issues related primarily to gallstone disease in pregnant patients will be reviewed
here. Detailed discussions on biliary disease in nonpregnant patients, which may
also apply to pregnant patients, are reviewed separately.
author: David C Brooks, MD
section editors: Stanley W Ashley, MD, Vincenzo Berghella, MD
deputy editors: Wenliang Chen, MD, PhD, Alana Chakrabarti, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.
This topic last updated: Apr 11, 2022.
(See "Gallstones: Epidemiology, risk factors and prevention".)●
27/02/2024, 20:05
Página 1 de 37
PATHOPHYSIOLOGY
During pregnancy, increased levels of reproductive hormones (eg, estrogen,
progesterone) induce a variety of physiologic changes in the biliary system that
promote gallstone formation [1-3]:
These changes normalize one to two months following delivery.
Symptoms related to gallstones develop when the gallbladder contracts in
response to hormonal or neural stimulation, usually due to a fatty meal.
Contraction forces stones (or possibly sludge or microlithiasis) against the
gallbladder outlet or cystic duct opening, leading to increased intra-gallbladder
pressure and pain ( figure 1). The stones often fall back from the cystic duct as
the gallbladder relaxes, with amelioration of symptoms.
A stone that passes through the ampulla of Vater can cause acute gallstone
pancreatitis, which is the most common cause of acute pancreatitis during
(See "Approach to the management of gallstones".)●
(See "Overview of gallstone disease in adults".)●
(See "Acute calculous cholecystitis: Clinical features and diagnosis".)●
(See "Treatment of acute calculous cholecystitis".)●
(See "Acalculous cholecystitis: Clinical manifestations, diagnosis, and
management".)
●
(See "Functional gallbladder disorder in adults".)●
(See "Choledocholithiasis: Clinical manifestations, diagnosis, and
management".)
●
(See "Management of acute pancreatitis", section on 'Gallstone pancreatitis'.)●
Estrogen increases cholesterol secretion and progesterone reduces bile acid
secretion, which ultimately causes bile to become supersaturated with
cholesterol. A relative overproduction of hydrophobic bile acids, such as
chenodeoxycholate, reduces the ability of bile to solubilize cholesterol.
●
Progesterone also slows gallbladder emptying, which further promotes the
formation of stones by causing bile stasis.
●
27/02/2024, 20:05
Página 2 de 37
pregnancy and is associated with maternal mortality if not recognized and treated
appropriately [4-8]. In a meta-analysis including 23 studies and almost 9000
patients with acute pancreatitis in pregnancy, maternal mortality occurred in 23
patients (0.26 percent); maternal mortality rate was higher in the first compared
with the second or third trimester [9]. (See 'Gallstone pancreatitis' below and
"Management of acute pancreatitis", section on 'Gallstone pancreatitis'.)
RISK FACTORS
Prepregnancy obesity [10,11] and multiparity [12-14] are independent risk factors
for gallstones in pregnancy. Other risk factors are similar to those of nonpregnant
patients ( table 2) [15,16].
Neither dietary fat intake nor physical activity seem to affect risk of gallstone
formation in pregnancy or up to four to six weeks postpartum [17]. Likewise,
efforts to decrease the likelihood of stones and sludge developing during
pregnancy by increasing metabolic expenditure have proven unsuccessful [18].
INCIDENCE AND COURSE
The reported incidence of gallstone-related disease in pregnant patients is low (detection of
common bile duct stones. (See "Overview of gallstone disease in adults", section
on 'Transabdominal ultrasound' and "Acute calculous cholecystitis: Clinical features
and diagnosis", section on 'Ultrasonography'.)
cholecystitis is similar to that in nonpregnant patients: RUQ or epigastric pain
that is steady and severe, prolonged (more than four to six hours), and
possibly radiating to the right shoulder or back. Associated symptoms
include fever, anorexia, nausea, and vomiting. Abdominal examination
usually demonstrates voluntary and involuntary guarding and, frequently, a
positive Murphy's sign. The constitutional symptoms and prolonged duration
of pain help to distinguish acute cholecystitis from biliary colic. (See
"Overview of gallstone disease in adults", section on 'Atypical symptoms' and
"Acute calculous cholecystitis: Clinical features and diagnosis", section on
'Clinical manifestations'.)
Biliary-type symptoms, no gallstones visible on ultrasound – Such
patients may have a pregnancy-related condition, such as preeclampsia with
severe features, or other causes of epigastric or right upper quadrant pain
(eg, peptic ulcer disease, choledocholithiasis, recently passed stone,
acalculous cholecystitis [which is rare during pregnancy]). (See 'Pregnancy-
related conditions' below and 'Non-pregnancy-related conditions' below and
"Acalculous cholecystitis: Clinical manifestations, diagnosis, and
management".)
●
27/02/2024, 20:05
Página 5 de 37
MRCP in select patients — Magnetic resonance cholangiopancreatography
(MRCP) is not typically used in the evaluation of biliary colic or acute cholecystitis
but may be useful in some complicated cases, such as patients with
choledocholithiasis or pancreatitis if ultrasound is nondiagnostic [28,29]. A routine
MRCP does not require any contrast agent such as gadolinium, and there are no
known harmful fetal effects of noncontrast magnetic resonance during pregnancy.
(See "Diagnostic imaging in pregnant and lactating patients".)
Other
Laboratory testing — Laboratory studies should be normal in patients with
uncomplicated gallstone disease, both during asymptomatic periods and during
attacks of pain; results need to be interpreted with respect to the normal range for
pregnant patients, which is sometimes different from the nonpregnant state (
table 3).
Thus, laboratories are obtained primarily to aid in the differential diagnosis.
Abnormal blood tests such as leukocytosis, elevated liver, or pancreas tests
HIDA scan – Cholescintigraphy using 99mTc-hepatic iminodiacetic acid
(generically referred to as a HIDA scan) is not a first-line imaging test in
patients with suspected gallstone-related disease and is rarely needed for
decision making. The fetal dose issyndrome (ie, Hemolysis, Elevated Liver enzymes, Low Platelet count),
acute fatty liver, abruptio placentae, uterine rupture, and intra-amniotic infection.
These conditions can usually be differentiated from gallstone disease by the
clinical setting in which they occur and by obtaining the appropriate diagnostic
studies. (See "Approach to acute abdominal/pelvic pain in pregnant and
postpartum patients".)
Preeclampsia/HELLP – Hypertension is the requisite criterion for
preeclampsia ( table 4) and is common in HELLP syndrome ( table 5).
Thrombocytopenia is a requisite criterion for HELLP syndrome and is
common in preeclampsia. Both disorders occur after 20 weeks of gestation.
Gallbladder disease is not associated with either hypertension or
thrombocytopenia and can occur anytime in pregnancy. Patients with
preeclampsia with severe features or HELLP syndrome can have elevated
liver enzymes (typically at least twice normal), which can also occur with
complicated gallstone disease. (See "Preeclampsia: Clinical features and
diagnosis" and "HELLP syndrome (hemolysis, elevated liver enzymes, and low
platelets)".)
●
Acute fatty liver – Acute fatty liver occurs in the second half of pregnancy,
usually in the third trimester. The most frequent initial symptoms are nausea
or vomiting (approximately 75 percent of patients), abdominal pain
(particularly epigastric, 50 percent), anorexia, and jaundice. Serum
aminotransferase elevations are usually higher in fatty liver than in
gallbladder disease, ranging from modest increases to up to 1000 IU/L.
About one-half of patients have signs of preeclampsia at presentation or at
●
27/02/2024, 20:05
Página 9 de 37
Non-pregnancy-related conditions — Non-pregnancy-related conditions include
non-gallstone-related biliary disease, gastroesophageal reflux, peptic ulcer
disease, hepatitis, and right-sided pneumonia. Of note, the location of the
appendix migrates cephalad with the enlarging uterus as shown in the figure (
figure 2); thus, appendicitis may be more likely to present with RUQ pain in
some time during the course of illness. Hypoglycemia is a feature of severe
acute fatty liver but is not present in preeclampsia, HELLP syndrome, or
gallbladder disease. Severe acute fatty liver is also characterized by renal
failure and disseminated intravascular coagulation, which are not features of
gallbladder disease. (See "Acute fatty liver of pregnancy".)
Abruption – An acute abruption (ie, decidual hemorrhage leading to the
premature separation of the placenta prior to delivery) classically presents
with vaginal bleeding, uterine contractions, and abdominal/uterine pain that
is typically not limited to the RUQ or epigastrium. In severe cases, the fetal
heart rate pattern is abnormal, and disseminated intravascular coagulation
occurs. These features distinguish abruption from gallbladder disease. (See
"Acute placental abruption: Pathophysiology, clinical features, diagnosis, and
consequences".)
●
Uterine rupture – Most uterine ruptures occur in laboring patients with a
prior cesarean delivery or prior transmyometrial surgery. Signs and
symptoms of uterine rupture can include an abnormal fetal heart rate tracing
or fetal death, uterine tenderness, peritoneal irritation, vaginal bleeding, and
shock. Uterine rupture prior to the onset of labor is rare and usually due to
sharp or blunt abdominal trauma. This clinical setting is quite different from
that in biliary disease. (See "Uterine rupture: After previous cesarean birth".)
●
Intra-amniotic infection – Signs and symptoms of intra-amniotic infection
include fever, abdominal pain, uterine tenderness, leukocytosis, maternal
and fetal tachycardia, and uterine contractions. Intra-amniotic infection is
common after premature rupture of the fetal membranes. Patients with
acute cholecystitis have some of these signs and symptoms, but the location
of pain is different (RUQ/epigastrium versus uterine) and the fetal
membranes are typically intact. (See "Clinical chorioamnionitis".)
●
27/02/2024, 20:05
Página 10 de 37
pregnancy. The differential diagnosis of RUQ or epigastric pain unrelated to
pregnancy is reviewed separately. (See "Causes of abdominal pain in adults" and
"Approach to acute abdominal/pelvic pain in pregnant and postpartum patients",
section on 'Upper abdominal pain'.)
MANAGEMENT
Most pregnant patients with gallstones are asymptomatic and do not require
further evaluation or treatment.
The management of symptomatic gallstone diseases during pregnancy is evolving.
In the past, nonoperative management was usually recommended, especially
during the first and third trimester. At present, early surgical or endoscopic
intervention is the treatment of choice for those with complicated gallstone
diseases (acute cholecystitis, choledocholithiasis/cholangitis, gallstone
pancreatitis), as well as those with progressive, intractable, or recurrent biliary
colic symptoms ( algorithm 1) [36].
However, management should be individualized based on the clinical scenario (ie,
uncomplicated versus complicated disease), gestational age, and other factors (eg,
local expertise, patient preference).
Treatment setting — Most pregnant patients with right upper abdominal pain
should be admitted to the hospital for pain control and fluid therapy and to rule
out other conditions, although some patients with mild biliary colic symptoms may
be initially managed in an outpatient setting.
Supportive care — Supportive care for all patients with symptomatic gallstone
diseases includes pain control, intravenous fluid therapy, and antibiotic therapy
(when clinically indicated). During an acute attack, patients should avoid eating,
which may exacerbate the pain by releasing cholecystokinin. (See 'Antibiotic
therapy' below and 'Pathophysiology' above.)
Pain control — Acetaminophen can be used to manage mild pain. More severe
pain can usually be controlled with opioids. Nonsteroidal anti-inflammatory drugs
(NSAIDs) are generally avoided in pregnancy, especially after 32 weeks of
27/02/2024, 20:05
Página 11 de 37
gestation, because of potential adverse fetal effects when used for more than 48
hours (eg, premature closure of the ductus arteriosus, oligohydramnios).
Antibiotic therapy — While empiric antibiotic therapy is generally not required
for biliary colic or mild gallstone pancreatitis, it is required for patients with acute
cholecystitis, cholangitis, or severe gallstone pancreatitis. Although acute
cholecystitis is primarily an inflammatory process, secondary infection of the
gallbladder can occur as a result of cystic duct obstruction and bile stasis. The
approach to antibiotic therapy in patients with acute cholecystitis and cholangitis
is discussed separately. (See "Treatment of acute calculous cholecystitis", section
on 'Antibiotics' and "Acute cholangitis: Clinical manifestations, diagnosis, and
management", section on 'Management'.)
The most frequent isolates from the gallbladder or common bile duct are
Escherichia coli, Enterococcus, Klebsiella, and Enterobacter.
Monotherapy with a beta-lactam/beta-lactamase inhibitor, such as one of the
following, is appropriate in pregnancy:
Cephalosporins, clindamycin, and aztreonam have a good safety profile in
pregnant patients. Aminoglycosides are relatively safe but carry a risk of fetal (and
maternal) ototoxicity and nephrotoxicity, so drug levels should be monitored.
Fluoroquinolones and carbapenems are generally avoided in pregnant patients
because of potential fetal toxicity.
Additional information about perioperative antibiotic use in pregnant patients is
Ampicillin-sulbactam 3 g intravenously every six hours, or●
Piperacillin-tazobactam 3.375 g intravenously every six hours, or●
An acceptable alternative is a third-generation cephalosporin, such as
ceftriaxone 1 g intravenously every 24 hours, plus metronidazole 500 mg
intravenously every eight hours. In patients who cannot take a penicillin or
cephalosporin, vancomycin 15 to 20 mg/kg/dose intravenously every 8 to12
hours initially (adjust based on therapeutic monitoring) plus aztreonam 1 to
2 g intravenously every 8 hours (maximum 8 g/day) plus metronidazole is an
accepted alternative.
●
27/02/2024, 20:05
Página 12 de 37
available elsewhere. (See "Prenatal care: Patient education, health promotion, and
safety of commonly used drugs", section on 'Antibiotics'.)
Biliary colic — The initial supportive management of biliary colic is usually
successful; patients are then encouraged to eat a well-balanced diet. Whether or
not a particular diet may reduce the formation and future risk of biliary colic is
unknown. Although ursodeoxycholic acid (UDCA) has been administered in the
management of intrahepatic cholestasis of pregnancy and has a good fetal safety
profile, its efficacy for the treatment of gallbladder stones during pregnancy has
not been well studied, and we do not use it in our practice. (See "Intrahepatic
cholestasis of pregnancy", section on 'Ursodeoxycholic acid'.)
For patients in whom supportive management is not successful, additional
imaging and repeat laboratory studies should be performed to exclude
complicated gallstone disease. If a complicated gallstone disease is diagnosed, or
symptoms of biliary colic (eg, pain, nausea/vomiting) cannot be controlled with
supportive care and dietary modification, gallbladder surgery should be promptly
offered and can be performed during any trimester. (See 'Cholecystectomy during
pregnancy' below.)
Whether all pregnant patients require gallbladder surgery after recovering from a
single bout of biliary colic is controversial ( algorithm 1):
Some of our contributors offer all such patients gallbladder surgery [37].
Rationale supporting this practice includes the following:
●
Delaying gallbladder surgery until after delivery incurs a high rate of
recurrences that require emergency room visits and/or hospitalization
[38-40]. Gallstone-related symptoms recur in 92, 64, and 44 percent of
patients who initially present in the first, second, and third trimester,
respectively [20,41].
•
Up to 27 percent of recurrences may involve complications such as acute
cholecystitis, cholangitis, or pancreatitis [38]. Complicated gallstone
diseases have been associated with preterm labor in 20 percent and fetal
loss in 10 to 60 percent of the patients [42].
•
27/02/2024, 20:05
Página 13 de 37
If biliary colic occurs near term, another reasonable option is to avoid
cholecystectomy and reevaluate the patient after delivery (see 'Incidence and
course' above). In that case, we suggest reimaging those who had uncomplicated
biliary colic during pregnancy with abdominal ultrasound four to six weeks
postpartum. Further management depends on findings on follow-up imaging
studies:
Postpartum cholecystectomy rates in patients with biliary colic during pregnancy
vary widely (0.8 to 56 percent) [11,23,43].
Acute cholecystitis — One of the most common clinical scenarios is a patient with
symptoms of cholecystitis and gallstones on ultrasound. Following supportive care
including antibiotic therapy, gallbladder surgery is indicated for any pregnant
patient with acute cholecystitis and can be safely performed during any trimester (
algorithm 1). For patients near term, a reasonable alternative is to defer
gallbladder surgery until after delivery, assuming that symptoms can be controlled
with antibiotics and supportive care. However, the risk of persistent, worsening, or
recurrent symptoms in such patients is unknown. (See 'Cholecystectomy during
Other contributors offer gallbladder surgery selectively to patients with
recurrent bouts of bothersome pain or those who are unable to gain weight
at an acceptable rate due to the symptoms [36].
●
If sludge/stones persist, we suggest performing cholecystectomy at least six
weeks after delivery to allow the mother to recover from the delivery and
bond with the infant but before three months after delivery to prevent
recurrent attacks of biliary colic or more severe complications. In such
patients, postpartum restoration of gallbladder motility may exacerbate
passage of sludge or stones from the gallbladder.
●
If sludge/stones disappear postpartum, it is reasonable to take a watchful
waiting approach while maintaining a low threshold for reimaging and
surgical intervention should any suggestion of symptoms recur. Dietary and
lifestyle measures that may reduce the risk of new gallstone formation are
reviewed separately. (See "Gallstones: Epidemiology, risk factors and
prevention", section on 'Prevention of gallstones'.)
●
27/02/2024, 20:05
Página 14 de 37
pregnancy' below.)
In a National Inpatient Sample (NIS) study including 23,939 pregnant patients with
acute cholecystitis from 2003 to 2015, approximately 36 percent were managed
nonoperatively while 60 and 4 percent underwent laparoscopic and open
cholecystectomy, respectively [44]. Compared with nonoperative management,
laparoscopic cholecystectomy for acute cholecystitis was associated with lower
rates of preterm delivery, labor, or abortion (odds ratio [OR] 0.41), and each day
that laparoscopic cholecystectomy was delayed was associated with an increased
risk of fetal complications (OR 1.17).
In a propensity score-matched study including 2719 pregnant patients with
cholecystitis, those who did not undergo cholecystectomy were more likely to have
maternal-fetal complications than those who underwent cholecystectomy both
during the index admission (27.6 versus 8 percent) and on 30 day readmission (7.9
versus 3.7 percent) [45]. Specifically, patients who did not undergo
cholecystectomy were over 6 times more likely to have poor fetal growth and over
3 times more likely to have either premature delivery or undergo cesarean
delivery. The readmission rate was higher among those who did not undergo
cholecystectomy (18.7 versus 10.7 percent), whereas the hospital stay was slightly
shorter (3.7 versus 4.5 days).
Other studies of pregnant patients with acute cholecystitis also associated early
cholecystectomy with reduced preterm delivery rate and readmission rate
compared with conservative management [46].
Choledocholithiasis/cholangitis — Patients with choledocholithiasis and/or
cholangitis are managed with supportive care (including antibiotic therapy) and
either (1) preoperative endoscopic retrograde cholangiopancreatography (ERCP)
followed by gallbladder surgery or (2) gallbladder surgery with either common bile
duct exploration or postoperative ERCP ( algorithm 1).
The two approaches are equally effective in the general population [47,48] but
have not been directly compared in pregnant patients. Both gallbladder surgery
and ERCP can be safely performed during any trimester, and the choice should be
based on local expertise [37].
27/02/2024, 20:05
Página 15 de 37
For patients who are near term, a reasonable option is to perform ERCP to extract
the common bile stone and relieve the common bile duct obstruction but defer
gallbladder surgery until after delivery. However, the risk of a recurrent episode of
choledocholithiasis is unknown.
Gallstone pancreatitis — Management of gallstone pancreatitis consists of initial
supportive care with hospitalization, pain control, intravenous fluid therapy, and
nutritional support ( algorithm 1). In a patient with biliary pancreatitis,
antibiotics are not required unless there is evidence of infection. (See
"Management of acute pancreatitis", section on 'Antibiotics' and 'Supportive care'
above.)
Gallstone pancreatitis will improve or resolve rapidly in many patients with
supportive treatment. A systematic review identified 12 studies that included a
total of 113 patients with confirmed gallstone-induced acute pancreatitis (study
dates: 1972 to 2004) [53,66-76]. Maternal mortality was no different for
conservative compared with surgical management, but fetal mortality trended
higher with conservative management compared with surgery (six versus two
cases) in patients who did not improve quickly [20]. Thus, patients who do notrespond promptly to supportive medical care, and those with concomitant
cholangitis, should undergo prompt ERCP and sphincterotomy with or without
ERCP with sphincterotomy can be performed with low rates of maternal or
fetal morbidity [49-52]. The efficacy of preoperative ERCP followed by
laparoscopic cholecystectomy has been validated by multiple studies in the
pregnant population [53-59]. ERCP generally uses fluoroscopy for imaging,
which can be accomplished safely during pregnancy with fetal shielding.
Exposure to ionizing radiation during ERCP can also be minimized or
eliminated by using specific techniques [60], which are discussed in detail
elsewhere. (See "Endoscopic retrograde cholangiopancreatography (ERCP) in
pregnancy".)
●
Good outcomes have been described with intraoperative common bile duct
exploration, but few cases have been reported for pregnant patients [61-64].
As with ERCP, the fetus should be shielded during intraoperative
cholangiography [65]. (See "Surgical common bile duct exploration".)
●
27/02/2024, 20:05
Página 16 de 37
biliary stent placement.
Cholecystectomy is also indicated, usually during the same hospitalization, for
patients with mild disease that resolves to prevent recurrence (up to 70 percent
[4]) and reduce costs [77]. Given that acute pancreatitis in pregnancy most
commonly occurs during the third trimester [4], for patients who are near term,
delaying gallbladder surgery until after delivery is a reasonable option [4,78].
CHOLECYSTECTOMY DURING PREGNANCY
Cholecystectomy can be performed safely and effectively during pregnancy. In
current practice, laparoscopic cholecystectomy is the preferred treatment for all
symptomatic gallstone diseases [37].
Timing — Traditionally, surgery was avoided during the first and third trimester to
minimize the risk of spontaneous abortion and preterm delivery, respectively [79].
Cholecystectomy, when indicated, was preferentially performed during the second
trimester [20,66,80-85]. This practice, however, was not evidence based.
Contemporary literature supports that laparoscopic surgery performed during any
trimester is safe for the mother and fetus [86,87]. Cholecystectomies performed
during the first trimester were not associated with a higher rate of complications
compared with those performed during the second trimester (adjusted odds ratio
[OR] 0.88, 95% CI 0.47-1.63) [88]. Laparoscopic cholecystectomy and
appendectomy performed late in the third trimester have also been reported
[86,87,89,90]. Consequently, major surgical [37] and obstetrical societies [91,92]
have switched their positions to endorsing necessary laparoscopic surgery during
any trimester.
However, cholecystectomy in the third trimester has been associated with
increased preterm delivery in several population studies:
In an administrative database study of the California statewide data, those
who underwent cholecystectomy during the third trimester had higher rates
of preterm delivery (OR 2.05), hospitalization (85 versus 63 percent),
readmission (OR 2.05), and open cholecystectomy (13 versus 2 percent), as
●
27/02/2024, 20:05
Página 17 de 37
Thus, while surgical management is the preferred approach for patients with
symptomatic gallstone disease near term, another option is to delay gallbladder
surgery until after delivery, as long as the presenting symptoms have been
adequately addressed by nonsurgical methods (eg, supportive treatment for
gallstone pancreatitis, endoscopic retrograde cholangiopancreatography [ERCP]
for choledocholithiasis or cholangitis). Patients should be explained the risks and
benefits of late-term versus postpartum gallbladder surgery to facilitate an
informed decision jointly with the treating surgeon and obstetrician.
Personnel and preparations — An experienced surgeon and anesthesiologist,
and early involvement of the patient's obstetrician, are important for providing
optimal outcomes for the mother and baby.
well as a longer hospital stay (+0.83 days), compared with patients who
underwent cholecystectomy postpartum [93].
In a similar study of the New York statewide data, patients who underwent
cholecystectomy during the third trimester also had a higher rate of preterm
delivery (OR 2.54) and a longer hospital stay (OR 1.44) compared with
patients who underwent cholecystectomy postpartum, but other outcomes
(eg, composite maternal outcomes, fetal demise, overall complication rate)
were not statistically different [94].
●
In a study of 819 patients from the National Inpatient Sample who
underwent cholecystectomy during pregnancy, cholecystectomies performed
during the third trimester were associated with a higher rate of preterm
delivery (adjusted OR 7.20, 95% CI 3.09-16.77) and overall maternal/fetal
complications (adjusted OR 2.78, 95% CI 1.71-4.53) compared with those
performed during the second trimester [88].
●
In a review of the Nationwide Inpatient Sample (NIS) database, surgical
treatment by high-volume surgeons (≥75 percentile) was associated with
fewer maternal complications and fetal complications than treatment by low-
volume surgeons (maternal complications 0.9 versus 14.3 percent; fetal
complications 3.9 versus 9.5 percent) [82].
●
th
Patients with uncomplicated gallbladder disease should be administered●
27/02/2024, 20:05
Página 18 de 37
Surgical approaches — In contemporary surgical practice, laparoscopic
cholecystectomy is the recognized standard for removal of the gallbladder and is
also the preferred technique in pregnant patients [37,65]. However, either an open
or laparoscopic approach to cholecystectomy may be chosen based upon uterine
size, maternal body habitus, past surgical history, surgeon experience, and the
availability of appropriate staff and equipment.
In general, a laparoscopic approach provides better surgical exposure than the
open approach during pregnancy and reduces the need to manipulate the uterus
away from the operative field. It also offers earlier recovery, reduced postoperative
pain with a reduction in opioid usage, smaller incisions, and fewer wound
complications such as hernia or surgical site infections [95,96].
Reviews of older studies comparing open with laparoscopic cholecystectomy
found no significant differences in maternal or fetal outcomes [8,20,53,79,82,96-
104]. In a 2016 systematic review and meta-analysis of 11 observational studies
(10,632 patients), laparoscopic compared with open cholecystectomy was
associated with decreased risks for fetal (OR 0.42, 95% CI 0.28-0.63), maternal (OR
0.42, 95% CI 0.33-0.53), and surgical (OR 0.45, 95% CI 0.25-0.82) complications and
a shorter length of stay (3.2 versus 6.0 days) [105]. However, 91 percent of the
patients underwent surgery during the first and second trimester.
If the laparoscopic procedure cannot be safely and/or effectively completed, the
prophylactic antibiotics prior to cholecystectomy, and those already receiving
antibiotics for complicated gallbladder disease should be re-dosed prior to
surgery. Appropriate antibiotic choices are discussed above. (See 'Antibiotic
therapy' above.)
Other anesthetic and preoperative considerations in the pregnant patient,
including positioning, fetal monitoring, thromboprophylaxis, and
pharmacologic management of preterm labor, are discussed in detail
elsewhere. Prophylactic tocolytic agents are not necessary [65]. (See
"Anesthesia for nonobstetric surgery during pregnancy" and "Nonobstetric
surgery in pregnant patients: Patient counseling, surgical considerations, and
obstetric management".)
●
27/02/2024, 20:05
Página 19 de 37
approach should be converted to an open cholecystectomy to avoid injury to
surrounding structures. This reflects good judgment and should not be viewed as
a failure or complication of the laparoscopic approach. Indications for choosing an
open surgical approach or conversion to an open procedure are discussed in detail
elsewhere. (See "Complications of laparoscopic surgery", section on 'Conversion to
an open procedure'.)Laparoscopic cholecystectomy — A few modifications to standard techniques
for laparoscopic cholecystectomy are needed when the patient is pregnant.
The remainder of the technique of laparoscopic cholecystectomy, including
intraoperative evaluation and laparoscopic management of common bile duct
stones, is similar to surgery in nonpregnant patients, as is shown in the figures
and discussed in detail elsewhere ( figure 5 and figure 6). (See "Laparoscopic
cholecystectomy", section on 'Evaluation for choledocholithiasis' and "Surgical
common bile duct exploration".)
Intraoperative cholangiography should be considered if the biliary anatomy is
unclear and/or if there is a substantial possibility of common bile duct stones.
Radiation exposure to the fetus is not significant if shielded by a lead apron (
figure 7) [65]. If available, intraoperative ultrasound of the bile duct can be
performed as an alternative to cholangiography and has equivalent diagnostic
accuracy for common duct stones in experienced hands.
Patients should be placed slightly head-up and tilted to their left, allowing the
uterus to fall away from the vena cava.
●
We prefer to use the open (Hasson) technique to gain initial access to the
abdomen. An alternative during the later stages of pregnancy is subcostal
access [65].
●
The trocars are generally placed in the usual locations, although as the
uterus enlarges in the third trimester ( figure 3), it can be advantageous to
move the epigastric port into the left upper quadrant to provide greater
perspective ( figure 4). This modification should be determined after
pneumoperitoneum has been established.
●
27/02/2024, 20:05
Página 20 de 37
Open cholecystectomy — The surgical technique of open cholecystectomy is
modified only slightly during pregnancy.
Postoperative care — General considerations for the postoperative care of
pregnant patients are reviewed separately. Fetal heart rate and uterine activity
should be assessed in the recovery room, as appropriate for gestational age. (See
"Laparoscopic surgery in pregnancy", section on 'Postoperative care' and
"Anesthesia for nonobstetric surgery during pregnancy", section on 'Postoperative
care'.)
Following cholecystectomy, the patient can usually resume drinking clear liquids
once the effects of anesthesia have worn off and then advance as tolerated to a
low-fat diet. Patients who have had laparoscopic surgery can usually be discharged
home on the day of surgery or the following day unless there are extenuating
circumstances, such as uterine contractions, vaginal bleeding, pain, or unremitting
nausea. A two- to four-day stay is usually necessary after open surgery.
Opioids and antiemetics can be used, as needed, to control postoperative pain and
nausea. Analgesic requirements should be met in consultation with the
obstetrician. Short-term use of acetaminophen or narcotics is safe in pregnancy,
although prolonged use of these medications (>2 weeks) postoperatively should
be avoided. Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided,
especially after 32 weeks of gestation, because they may cause premature closure
of the fetal ductus arteriosus. Epidural analgesia is an option for postoperative
pain control after an open procedure and carries less risk of opioid-induced
hypoventilation when compared with intravenous opioids. (See "Prenatal care:
Patient education, health promotion, and safety of commonly used drugs", section
on 'Pain and fever medications'.)
Patients are placed slightly head-up and tilted toward the left, allowing the
uterus to fall away from the inferior vena cava.
●
A subcostal incision is preferred as it allows an easier approach to the
gallbladder when the uterus is very large.
●
The procedure is otherwise performed in standard fashion, as discussed in
detail elsewhere. (See "Open cholecystectomy".)
●
27/02/2024, 20:05
Página 21 de 37
Outcomes
Maternal-fetal safety — Cholecystectomy during pregnancy appears to be safe
for the mother and fetus [39]. Specifically, surgical intervention is not associated
with a higher risk of premature labor and/or delivery (prevalence 0 to 10 percent)
than that in the general obstetrical population [20,66,84,106,107]. Nor is
cholecystectomy associated with a higher risk of maternal or fetal mortality than
nonoperative management of symptomatic gallstone disease during pregnancy
[107]. In a 2009 study of 9714 pregnant patients who underwent cholecystectomy,
the overall rates of maternal or fetal complications were 4.3 and 5.8 percent,
respectively [82].
Surgical complications — Pregnancy alone does not appear to increase
postoperative surgical morbidity for cholecystectomy in pregnant compared with
nonpregnant patients [108,109].
Comparison with nonoperative treatment — Although randomized trials of the
surgical treatment of biliary disease in pregnant patients have never been
performed, observational data support that an early intervention approach is
equally safe and more effective than expectant management/supportive medical
therapy [110,111]. This conclusion is congruent with similar findings in the general
population where higher-quality evidence exists.
In a review of data from the American College of Surgeons database from
2005 to 2009, composite 30 day major morbidity was similar after
cholecystectomy between pregnant and nonpregnant patients at 1.8 percent
[108].
●
In a review of the NIS that compared cholecystectomy in 9714 pregnant with
53,598 nonpregnant female controls from 1996 to 2006, pregnant patients
had higher rates of unadjusted surgical complications (10.7 versus 9.6
percent) [82]. However, after adjustment for patient and provider
characteristics, pregnancy was not a significant predictor for having a
surgical complication but was an independent predictor for longer adjusted
length of stay.
●
A retrospective analysis of hospital discharges from 1999 to 2006 from the●
27/02/2024, 20:05
Página 22 de 37
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries
and regions around the world are provided separately. (See "Society guideline
links: Gallbladder surgery" and "Society guideline links: Gallstones".)
SUMMARY AND RECOMMENDATIONS
Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-
NIS) identified 36,929 pregnant patients hospitalized with biliary tract disease
(eg, gallstones, cholecystitis, cholangitis, biliary pancreatitis, other biliary
diseases) [82]. Of these, 9714 underwent cholecystectomy; most (89 percent)
were performed laparoscopically. Surgical treatment was associated with
lower complication rates than nonoperative management (maternal
complication rate 4.3 versus 16.5 percent; fetal complication rate 5.8 versus
16.5 percent). However, the choice of surgery versus nonoperative
management and laparoscopic versus open surgery in this retrospective
study likely reflects patient-specific factors, such as the type and severity of
gallstone-related disease; thus, the results cannot be used alone to guide
decision making [112].
Medical management of symptomatic gallstone diseases has been
associated with an increased risk of cesarean delivery. In one small
retrospective review of 112 pregnant patients who presented with
complications of gallstone disease (eg, acute cholecystitis,
choledocholithiasis, pancreatitis), the cesarean delivery rate was significantly
higher in those treated conservatively (n = 68) compared with those
undergoing surgery, ERCP, or both (34 versus 8 percent) [39]. This may have
been due to an increased frequency of labor induction in conservatively
treated patients.
●
Gallstones are common during pregnancy due to decreased gallbladder
motility and increased cholesterol saturation of bile. The major independent
risk factors for gallstones are prepregnancy obesity and multiparity. (See
●
27/02/2024, 20:05
Página 23 de 37
'Pathophysiology' above and 'Risk factors' above.)
The clinical presentation of gallstone diseaseduring pregnancy is similar to
that of nonpregnant patients. Among pregnant patients who develop
gallstones or have sludge, approximately 1 percent develop symptoms. In
most patients, recurrent right upper quadrant (RUQ) pain (biliary colic) is the
first symptom related to gallstones. Less frequently, initial manifestations
may be related to complications of gallstones (ie, acute cholecystitis,
cholangitis, gallstone pancreatitis). (See 'Clinical presentation' above.)
●
The criteria for diagnosis of gallstone-related diseases in pregnancy are the
same as in nonpregnant patients. Ultrasonography is a reliable and safe
method for identifying stones in the gallbladder. Common bile duct stones
are poorly identified with transabdominal ultrasound. Other imaging that
may be useful and is considered safe in pregnancy includes magnetic
resonance cholangiopancreatography (MRCP) and cholescintigraphy (HIDA
scan). (See 'Diagnosis' above and 'Abdominal imaging' above.)
●
Laboratory studies can be helpful for diagnosing complicated gallbladder
disease and excluding other pregnancy- and non-pregnancy-related
conditions. Routine laboratory studies are generally normal in patients with
uncomplicated biliary colic. Significant elevations of the transaminases and
alkaline phosphatase or direct bilirubin should raise the possibility of a
common bile duct stone, cholangitis, or Mirizzi syndrome; results need to be
interpreted with respect to the normal range for pregnant patients, which is
sometimes different from the nonpregnant state ( table 3). (See
'Laboratory testing' above.)
●
In pregnant patients with RUQ or epigastric pain, pregnancy-related
conditions (eg, preeclampsia with severe features and HELLP syndrome [ie,
Hemolysis, Elevated Liver enzymes, Low Platelet count], acute fatty liver,
abruptio placentae, uterine rupture, and intra-amniotic infection) must be
considered, even if gallstones are observed on ultrasound examination, since
they may be an incidental finding. These conditions can usually be
differentiated from gallstone disease using the clinical setting in which they
occur. (See 'Differential diagnosis' above.)
●
27/02/2024, 20:05
Página 24 de 37
Most gallstones in pregnancy are asymptomatic and require no further
evaluation or treatment. Pregnant patients who are symptomatic are typically
admitted to the hospital for pain control, intravenous fluid therapy, antibiotic
therapy (for acute cholecystitis or cholangitis only), and possible surgical
intervention ( algorithm 1). (See 'Treatment setting' above and 'Supportive
care' above.)
●
Most patients with uncomplicated gallstone disease (ie, biliary colic) improve
with supportive therapy, which includes pain control and intravenous fluid.
Subsequent management and timing of elective surgery is controversial;
some of our contributors offer cholecystectomy during pregnancy to all
symptomatic patients (even if only a single episode), while others offer
cholecystectomy only to those with progressive, intractable, or recurrent
symptoms ( algorithm 1). (See 'Biliary colic' above.)
●
For most pregnant patients with complicated gallstone diseases (acute
cholecystitis, choledocholithiasis or cholangitis, gallstone pancreatitis), we
suggest early intervention (gallbladder surgery or endoscopic retrograde
cholangiopancreatography [ERCP]) rather than nonoperative medical
management ( algorithm 1) (Grade 2C). However, delaying gallbladder
surgery until after delivery is a reasonable alternative for some patients near
term. In several population studies, cholecystectomy during the third
trimester has been associated with increased risk of preterm delivery
compared with postpartum surgery. Additional considerations include
disease severity and surgical expertise as well as patient preferences. (See
'Acute cholecystitis' above and 'Choledocholithiasis/cholangitis' above and
'Gallstone pancreatitis' above and 'Timing' above.)
●
Cholecystectomy can be performed safely and effectively during any
trimester of pregnancy but requires an experienced surgeon, anesthesia
provider, and early involvement of an obstetrician. Pregnancy alone does not
appear to increase postoperative morbidity for cholecystectomy, nor does
cholecystectomy jeopardize maternal-fetal safety. (See 'Cholecystectomy
during pregnancy' above.)
●
For pregnant patients who undergo cholecystectomy, we suggest a●
27/02/2024, 20:05
Página 25 de 37
Use of UpToDate is subject to the Terms of Use.
REFERENCES
1. Everson GT. Pregnancy and gallstones. Hepatology 1993; 17:159.
2. Everson GT. Gastrointestinal motility in pregnancy. Gastroenterol Clin North
Am 1992; 21:751.
3. Kern F Jr, Everson GT, DeMark B, et al. Biliary lipids, bile acids, and gallbladder
function in the human female. Effects of pregnancy and the ovulatory cycle. J
Clin Invest 1981; 68:1229.
4. Ducarme G, Maire F, Chatel P, et al. Acute pancreatitis during pregnancy: a
review. J Perinatol 2014; 34:87.
5. Howden JK, Baillie J. Preoperative versus postoperative endoscopic
retrograde cholangiopancreatography in mild to moderate pancreatitis: a
prospective randomized trial. Gastrointest Endosc 2001; 53:834.
6. Working Party of the British Society of Gastroenterology, Association of
Surgeons of Great Britain and Ireland, Pancreatic Society of Great Britain and
Ireland, Association of Upper GI Surgeons of Great Britain and Ireland. UK
guidelines for the management of acute pancreatitis. Gut 2005; 54 Suppl
3:iii1.
7. Pitchumoni CS, Yegneswaran B. Acute pancreatitis in pregnancy. World J
Gastroenterol 2009; 15:5641.
8. Ghumman E, Barry M, Grace PA. Management of gallstones in pregnancy. Br J
Surg 1997; 84:1646.
laparoscopic approach rather than open surgery, when feasible and available
(Grade 1B). Laparoscopic surgery has been shown to improve patient
outcomes without increasing surgical, maternal, or fetal complication rates.
(See 'Surgical approaches' above.)
27/02/2024, 20:05
Página 26 de 37
9. Hughes DL, Hughes A, White PB, Silva MA. Acute pancreatitis in pregnancy:
meta-analysis of maternal and fetal outcomes. Br J Surg 2021; 109:12.
10. Igbinosa O, Poddar S, Pitchumoni C. Pregnancy associated pancreatitis
revisited. Clin Res Hepatol Gastroenterol 2013; 37:177.
11. Ko CW, Beresford SA, Schulte SJ, et al. Incidence, natural history, and risk
factors for biliary sludge and stones during pregnancy. Hepatology 2005;
41:359.
12. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis:
pathogenesis and natural course of gallstones diagnosed in early
puerperium. Hepatology 1993; 17:1.
13. Barbara L, Sama C, Morselli Labate AM, et al. A population study on the
prevalence of gallstone disease: the Sirmione Study. Hepatology 1987; 7:913.
14. Liu B, Beral V, Balkwill A, Million Women Study Collaborators. Childbearing,
breastfeeding, other reproductive factors and the subsequent risk of
hospitalization for gallbladder disease. Int J Epidemiol 2009; 38:312.
15. Maringhini A, Ciambra M, Baccelliere P, et al. Biliary sludge and gallstones in
pregnancy: incidence, risk factors, and natural history. Ann Intern Med 1993;
119:116.
16. Fell GL, Brooks D. Gallstone and biliary disease. In: Gastrointestinal and Liver
Disorders in Women’s Health, Beniwal-Patel P, Shaker R (Eds), Springer, Cha
m, Switzerland 2019. p.331.
17. Mathew LK, Ko C. Dietary fat and protein intake are not associated with
incident biliary sludge and stones during pregnancy. JPEN J Parenter Enteral
Nutr 2015; 39:124.
18. Ko CW, Napolitano PG, Lee SP, et al. Physical activity, maternal metabolic
measures, and the incidence of gallbladder sludge or stones during
pregnancy: a randomized trial. Am J Perinatol 2014; 31:39.
19. Ellington SR, Flowers L, Legardy-Williams JK, et al. Recent trends in hepatic
27/02/2024, 20:05
Página 27 de 37
diseases during pregnancy in the United States, 2002-2010. Am J Obstet
Gynecol 2015; 212:524.e1.
20. Date RS, Kaushal M, Ramesh A. A review of the management of gallstone
disease and its complicationsin pregnancy. Am J Surg 2008; 196:599.
21. Elamin Ali M, Yahia Al-Shehri M, Abu-Eshy S, et al. Is surgical intervention in
acute cholecystitis in pregnancy justified? J Obstet Gynaecol 1997; 17:435.
22. Mendez-Sanchez N, Chavez-Tapia NC, Uribe M. Pregnancy and gallbladder
disease. Ann Hepatol 2006; 5:227.
23. Galyani Moghaddam T, Fakheri H, Abdi R, et al. The incidence and outcome of
pregnancy-related biliary sludge/stones and potential risk factors. Arch Iran
Med 2013; 16:12.
24. Maringhini A, Marcenò MP, Lanzarone F, et al. Sludge and stones in
gallbladder after pregnancy. Prevalence and risk factors. J Hepatol 1987;
5:218.
25. Ramin KD, Ramsey PS. Disease of the gallbladder and pancreas in pregnancy.
Obstet Gynecol Clin North Am 2001; 28:571.
26. Boregowda G, Shehata HA. Gastrointestinal and liver disease in pregnancy.
Best Pract Res Clin Obstet Gynaecol 2013; 27:835.
27. Gilo NB, Amini D, Landy HJ. Appendicitis and cholecystitis in pregnancy. Clin
Obstet Gynecol 2009; 52:586.
28. Oto A, Ernst R, Ghulmiyyah L, et al. The role of MR cholangiopancreatography
in the evaluation of pregnant patients with acute pancreaticobiliary disease.
Br J Radiol 2009; 82:279.
29. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed
tomography and magnetic resonance imaging use during pregnancy and
lactation. Obstet Gynecol 2008; 112:333.
30. Adelstein SJ. Administered radionuclides in pregnancy. Teratology 1999;
59:236.
27/02/2024, 20:05
Página 28 de 37
31. Kurzweil SM, Shapiro MJ, Andrus CH, et al. Hyperbilirubinemia without
common bile duct abnormalities and hyperamylasemia without pancreatitis
in patients with gallbladder disease. Arch Surg 1994; 129:829.
32. Larsson A, Palm M, Hansson LO, Axelsson O. Reference values for clinical
chemistry tests during normal pregnancy. BJOG 2008; 115:874.
33. Kaiser R, Berk JE, Fridhandler L. Serum amylase changes during pregnancy.
Am J Obstet Gynecol 1975; 122:283.
34. Strickland DM, Hauth JC, Widish J, et al. Amylase and isoamylase activities in
serum of pregnant women. Obstet Gynecol 1984; 63:389.
35. Karsenti D, Bacq Y, Bréchot JF, et al. Serum amylase and lipase activities in
normal pregnancy: a prospective case-control study. Am J Gastroenterol
2001; 96:697.
36. Schwulst SJ, Son M. Management of Gallstone Disease During Pregnancy.
JAMA Surg 2020; 155:1162.
37. Pearl JP, Price RR, Tonkin AE, et al. SAGES guidelines for the use of
laparoscopy during pregnancy. Surg Endosc 2017; 31:3767.
38. Jorge AM, Keswani RN, Veerappan A, et al. Non-operative management of
symptomatic cholelithiasis in pregnancy is associated with frequent
hospitalizations. J Gastrointest Surg 2015; 19:598.
39. Othman MO, Stone E, Hashimi M, Parasher G. Conservative management of
cholelithiasis and its complications in pregnancy is associated with recurrent
symptoms and more emergency department visits. Gastrointest Endosc
2012; 76:564.
40. Veerappan A, Gawron AJ, Soper NJ, Keswani RN. Delaying cholecystectomy for
complicated gallstone disease in pregnancy is associated with recurrent
postpartum symptoms. J Gastrointest Surg 2013; 17:1953.
41. Steinbrook RA, Brooks DC, Datta S. Laparoscopic cholecystectomy during
pregnancy. Review of anesthetic management, surgical considerations. Surg
27/02/2024, 20:05
Página 29 de 37
Endosc 1996; 10:511.
42. Nasioudis D, Tsilimigras D, Economopoulos KP. Laparoscopic cholecystectomy
during pregnancy: A systematic review of 590 patients. Int J Surg 2016;
27:165.
43. Hedström J, Nilsson J, Andersson R, Andersson B. Changing management of
gallstone-related disease in pregnancy - a retrospective cohort analysis.
Scand J Gastroenterol 2017; 52:1016.
44. Cheng V, Matsushima K, Sandhu K, et al. Surgical trends in the management
of acute cholecystitis during pregnancy. Surg Endosc 2021; 35:5752.
45. Rios-Diaz AJ, Oliver EA, Bevilacqua LA, et al. Is It Safe to Manage Acute
Cholecystitis Nonoperatively During Pregnancy?: A Nationwide Analysis of
Morbidity According to Management Strategy. Ann Surg 2020; 272:449.
46. Barut B, Gönültaş F, Gök AFK, Şahin TT. Management of Acute Cholecystitis
During Pregnancy: A Single Center Experience. Ulus Travma Acil Cerrahi Derg
2019; 25:154.
47. Tan C, Ocampo O, Ong R, Tan KS. Comparison of one stage laparoscopic
cholecystectomy combined with intra-operative endoscopic sphincterotomy
versus two-stage pre-operative endoscopic sphincterotomy followed by
laparoscopic cholecystectomy for the management of pre-operatively
diagnosed patients with common bile duct stones: a meta-analysis. Surg
Endosc 2018; 32:770.
48. Vettoretto N, Arezzo A, Famiglietti F, et al. Laparoscopic-endoscopic
rendezvous versus preoperative endoscopic sphincterotomy in people
undergoing laparoscopic cholecystectomy for stones in the gallbladder and
bile duct. Cochrane Database Syst Rev 2018; 4:CD010507.
49. Azab M, Bharadwaj S, Jayaraj M, et al. Safety of endoscopic retrograde
cholangiopancreatography (ERCP) in pregnancy: A systematic review and
meta-analysis. Saudi J Gastroenterol 2019; 25:341.
50. Akcakaya A, Koc B, Adas G, Kemik O. The use of ERCP during pregnancy: is it
27/02/2024, 20:05
Página 30 de 37
safe and effective? Hepatogastroenterology 2014; 61:296.
51. Zhou Y, Zhang X, Zhang X, et al. ERCP in acute cholangitis during third
trimester of pregnancy. Hepatogastroenterology 2013; 60:981.
52. Park ET. Endoscopic Retrograde Cholangiopancreatography during
Pregnancy: Really Guarantee to Safety? Gut Liver 2015; 9:569.
53. Cosenza CA, Saffari B, Jabbour N, et al. Surgical management of biliary
gallstone disease during pregnancy. Am J Surg 1999; 178:545.
54. Sungler P, Heinerman PM, Steiner H, et al. Laparoscopic cholecystectomy and
interventional endoscopy for gallstone complications during pregnancy. Surg
Endosc 2000; 14:267.
55. Baillie J, Cairns SR, Putman WS, Cotton PB. Endoscopic management of
choledocholithiasis during pregnancy. Surg Gynecol Obstet 1990; 171:1.
56. Barthel JS, Chowdhury T, Miedema BW. Endoscopic sphincterotomy for the
treatment of gallstone pancreatitis during pregnancy. Surg Endosc 1998;
12:394.
57. Scapa E. To do or not to do an endoscopic retrograde
cholangiopancreatography in acute biliary pancreatitis? Surg Laparosc
Endosc 1995; 5:453.
58. Andreoli M, Sayegh SK, Hoefer R, et al. Laparoscopic cholecystectomy for
recurrent gallstone pancreatitis during pregnancy. South Med J 1996;
89:1114.
59. Fine S, Beirne J, Delgi-Esposti S, Habr F. Continued evidence for safety of
endoscopic retrograde cholangiopancreatography during pregnancy. World J
Gastrointest Endosc 2014; 6:352.
60. Cappell MS, Stavropoulos SN, Friedel D. Systematic review of safety and
efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography
during pregnancy including studies of radiation-free therapeutic endoscopic-
retrograde-cholangiopancreatography. World J Gastrointest Endosc 2018;
27/02/2024, 20:05
Página 31 de 37
10:308.
61. Kim YW, Zagorski SM, Chung MH. Laparoscopic common bile duct exploration
in pregnancy with acute gallstone pancreatitis. JSLS 2006; 10:78.
62. Liberman MA, Phillips EH, Carroll B, et al. Management of choledocholithiasis
during pregnancy: a new protocol in the laparoscopic era. J Laparoendosc
Surg 1995; 5:399.
63. DePaula AL, Hashiba K, Bafutto M. Laparoscopic management of
choledocholithiasis. Surg Endosc 1994; 8:1399.
64. Tuech JJ, Binelli C, Aube C, et al. Management of choledocholithiasis during
pregnancy by magnetic resonance cholangiography and laparoscopic
common bile duct stone extraction. Surg Laparosc Endosc Percutan Tech
2000; 10:323.
65. Guidelines for Laparoscopic Surgery During Pregnancy. Los Angeles, CA: Soci
ety of American Gastrointestinal Endoscopic Surgeons. Available at: http://w
ww.sages.org/publications/guidelines/guidelines-for-diagnosis-treatment-an
d-use-of-laparoscopy-for-surgical-problems-during-pregnancy/ (Accessed on J
uly 03, 2014).
66. Lu EJ, Curet MJ, El-Sayed YY, Kirkwood KS. Medical versus surgical
management of biliary tractdisease in pregnancy. Am J Surg 2004; 188:755.
67. Ramin KD, Ramin SM, Richey SD, Cunningham FG. Acute pancreatitis in
pregnancy. Am J Obstet Gynecol 1995; 173:187.
68. Chen CP, Wang KG, Su TH, Yang YC. Acute pancreatitis in pregnancy. Acta
Obstet Gynecol Scand 1995; 74:607.
69. Wilkinson EJ. Acute pancreatitis in pregnancy: a review of 98 cases and a
report of 8 new cases. Obstet Gynecol Surv 1973; 28:281.
70. Robertson KW, Stewart IS, Imrie CW. Severe acute pancreatitis and
pregnancy. Pancreatology 2006; 6:309.
71. Swisher SG, Hunt KK, Schmit PJ, et al. Management of pancreatitis
27/02/2024, 20:05
Página 32 de 37
complicating pregnancy. Am Surg 1994; 60:759.
72. Legro RS, Laifer SA. First-trimester pancreatitis. Maternal and neonatal
outcome. J Reprod Med 1995; 40:689.
73. Block P, Kelly TR. Management of gallstone pancreatitis during pregnancy
and the postpartum period. Surg Gynecol Obstet 1989; 168:426.
74. McKay AJ, O'Neill J, Imrie CW. Pancreatitis, pregnancy and gallstones. Br J
Obstet Gynaecol 1980; 87:47.
75. Jouppila P, Mokka R, Larmi TK. Acute pancreatitis in pregnancy. Surg Gynecol
Obstet 1974; 139:879.
76. Corlett RC Jr, Mishell DR Jr. Pancreatitis in pregnancy. Am J Obstet Gynecol
1972; 113:281.
77. Juo YY, Khrucharoen U, Sanaiha Y, et al. Cumulative Financial Burden of
Readmissions for Biliary Pancreatitis in Pregnant Women. Obstet Gynecol
2018; 132:415.
78. Mali P. Pancreatitis in pregnancy: etiology, diagnosis, treatment, and
outcomes. Hepatobiliary Pancreat Dis Int 2016; 15:434.
79. Graham G, Baxi L, Tharakan T. Laparoscopic cholecystectomy during
pregnancy: a case series and review of the literature. Obstet Gynecol Surv
1998; 53:566.
80. Glasgow RE, Visser BC, Harris HW, et al. Changing management of gallstone
disease during pregnancy. Surg Endosc 1998; 12:241.
81. Davis A, Katz VL, Cox R. Gallbladder disease in pregnancy. J Reprod Med 1995;
40:759.
82. Kuy S, Roman SA, Desai R, Sosa JA. Outcomes following cholecystectomy in
pregnant and nonpregnant women. Surgery 2009; 146:358.
83. Jelin EB, Smink DS, Vernon AH, Brooks DC. Management of biliary tract
disease during pregnancy: a decision analysis. Surg Endosc 2008; 22:54.
27/02/2024, 20:05
Página 33 de 37
84. Dhupar R, Smaldone GM, Hamad GG. Is there a benefit to delaying
cholecystectomy for symptomatic gallbladder disease during pregnancy?
Surg Endosc 2010; 24:108.
85. Chiappetta Porras LT, Nápoli ED, Canullán CM, et al. Minimally invasive
management of acute biliary tract disease during pregnancy. HPB Surg 2009;
2009:829020.
86. Geisler JP, Rose SL, Mernitz CS, et al. Non-gynecologic laparoscopy in second
and third trimester pregnancy: obstetric implications. JSLS 1998; 2:235.
87. Weiner E, Mizrachi Y, Keidar R, et al. Laparoscopic surgery performed in
advanced pregnancy compared to early pregnancy. Arch Gynecol Obstet
2015; 292:1063.
88. Cheng V, Matsushima K, Ashbrook M, et al. Association Between Trimester
and Outcomes after Cholecystectomy During Pregnancy. J Am Coll Surg 2021;
233:29.
89. Upadhyay A, Stanten S, Kazantsev G, et al. Laparoscopic management of a
nonobstetric emergency in the third trimester of pregnancy. Surg Endosc
2007; 21:1344.
90. Halkic N, Tempia-Caliera AA, Ksontini R, et al. Laparoscopic management of
appendicitis and symptomatic cholelithiasis during pregnancy. Langenbecks
Arch Surg 2006; 391:467.
91. Ball E, Waters N, Cooper N, et al. Evidence-Based Guideline on Laparoscopy in
Pregnancy: Commissioned by the British Society for Gynaecological
Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians &
Gynaecologists (RCOG). Facts Views Vis Obgyn 2019; 11:5.
92. ACOG Committee Opinion No. 775: Nonobstetric Surgery During Pregnancy.
Obstet Gynecol 2019; 133:e285.
93. Fong ZV, Pitt HA, Strasberg SM, et al. Cholecystectomy During the Third
Trimester of Pregnancy: Proceed or Delay? J Am Coll Surg 2019; 228:494.
27/02/2024, 20:05
Página 34 de 37
94. Hong J, Yang J, Zhang X, et al. Considering delay of cholecystectomy in the
third trimester of pregnancy. Surg Endosc 2021; 35:4673.
95. Corneille MG, Gallup TM, Bening T, et al. The use of laparoscopic surgery in
pregnancy: evaluation of safety and efficacy. Am J Surg 2010; 200:363.
96. Curet MJ. Special problems in laparoscopic surgery. Previous abdominal
surgery, obesity, and pregnancy. Surg Clin North Am 2000; 80:1093.
97. Nezhat FR, Tazuke S, Nezhat CH, et al. Laparoscopy during pregnancy: a
literature review. JSLS 1997; 1:17.
98. Reedy MB, Källén B, Kuehl TJ. Laparoscopy during pregnancy: a study of five
fetal outcome parameters with use of the Swedish Health Registry. Am J
Obstet Gynecol 1997; 177:673.
99. Lanzafame RJ. Laparoscopic cholecystectomy during pregnancy. Surgery
1995; 118:627.
100. Lachman E, Schienfeld A, Voss E, et al. Pregnancy and laparoscopic surgery. J
Am Assoc Gynecol Laparosc 1999; 6:347.
101. Affleck DG, Handrahan DL, Egger MJ, Price RR. The laparoscopic management
of appendicitis and cholelithiasis during pregnancy. Am J Surg 1999; 178:523.
102. Rollins MD, Chan KJ, Price RR. Laparoscopy for appendicitis and cholelithiasis
during pregnancy: a new standard of care. Surg Endosc 2004; 18:237.
103. Conron RW Jr, Abbruzzi K, Cochrane SO, et al. Laparoscopic procedures in
pregnancy. Am Surg 1999; 65:259.
104. Barone JE, Bears S, Chen S, et al. Outcome study of cholecystectomy during
pregnancy. Am J Surg 1999; 177:232.
105. Sedaghat N, Cao AM, Eslick GD, Cox MR. Laparoscopic versus open
cholecystectomy in pregnancy: a systematic review and meta-analysis. Surg
Endosc 2017; 31:673.
106. Tang SJ, Mayo MJ, Rodriguez-Frias E, et al. Safety and utility of ERCP during
27/02/2024, 20:05
Página 35 de 37
pregnancy. Gastrointest Endosc 2009; 69:453.
107. Athwal R, Bhogal RH, Hodson J, Ramcharan S. Surgery for gallstone disease
during pregnancy does not increase fetal or maternal mortality: a meta-
analysis. Hepatobiliary Surg Nutr 2016; 5:53.
108. Silvestri MT, Pettker CM, Brousseau EC, et al. Morbidity of appendectomy and
cholecystectomy in pregnant and nonpregnant women. Obstet Gynecol 2011;
118:1261.
109. McKellar DP, Anderson CT, Boynton CJ, Peoples JB. Cholecystectomy during
pregnancy without fetal loss. Surg Gynecol Obstet 1992; 174:465.
110. Pearl JP, Price R, Stefanidis D. Limitations of Existing Literature on
Laparoscopy in Pregnancy. J Am Coll Surg 2019; 229:439.
111. Chamberlain SL, Croagh D. Managing choledocholithiasis in pregnancy: a
novel approach. BMJ Case Rep 2020; 13.
112. Bowie JM, Calvo RY, Bansal V, et al. Association of complicated gallstone
disease in pregnancy and adverse birth outcomes. Am J Surg 2020; 220:745.
Topic 15095 Version 38.0
27/02/2024, 20:05
Página 36 de 37
27/02/2024, 20:05
Página 37 de 37