Teratogenic Effects of Ionizing Radiation

Teratogenic effects of radiation can be seen during early organogenesis in animal studies. Exposure of

rats to 100 rads at various points of development reveals a very narrow window for teratogenesis. This

window corresponds to weeks 2 to 4 in human development, consistent with early organ formation.

Despite these experimental data, it is difficult to link any specific human malformation with radiation

exposure other than those of the CNS. Microcephaly, pigmentary changes in the retina, hydrocephalus,

and optic nerve atrophy have been reported at a significantly higher rate after exposure to radiation in

pregnancy.54 All patients were exposed to a minimum estimated dose of 100 rads, and no visceral, limb,

or other malformations were found unless the child also exhibited CNS abnormalities. One explanation

for this discrepancy is that the developmental period of the CNS is much longer, continuing throughout

gestation and into the neonatal period, whereas other organs have a very narrow period during which

morphologic alterations can be produced. Exposure to high doses of radiation during this narrow

window is rare, and even if an isolated congenital abnormality were to occur, it would be difficult to

separate this event from the background malformation rate. The extended period for CNS sensitivity to

teratogenesis increases the prevalence of CNS malformation. Central nervous system malformation also

occurs at threshold doses; however, low levels of exposure to 10 to 20 rads of radiation do not increase

the incidence of microcephaly in experimental animals over baseline.55

Growth Retardation from Ionizing Radiation

Growth retardation results from radiation-induced cellular depletion. Although catch-up growth can

occur if exposure happens early in gestation, permanent cell depletion and growth retardation occur

with exposure during later fetal stages.56 Wood and colleagues

58 studied growth retardation of children

exposed in utero to the Japanese atomic blasts. Those within 1,500 m from the center of the explosion

were exposed to over 25 rads and, when followed through age of 17 years, were 2 to 3 cm shorter and

3 kg lighter and had a head circumference 1-cm smaller than normal. Those beyond 1,500 m from the

blast received less than 25 rads and had a normal head circumference, height, and weight.52,57,58

Further, animal and human data support the contention that exposures of less than 5 rads should not

cause either anatomic malformation or growth retardation.55

Oncogenic Potential of Ionizing Radiation

The correlation between childhood cancer and in utero exposure to radiation has been demonstrated.

Although conclusions regarding the cause-and-effect relationship of this correlation cannot be

definitively established, further studies using twins

59 and extensive data analysis

60 have strengthened

the argument that in utero radiation can increase the rate of childhood cancer even at doses of 1 rad.

The current increase in childhood cancer is estimated at one to two cases per 3,000 children exposed to

1 rad in utero.57 Although these risks are very small, the patient must be counseled regarding this

potential danger. By reviewing the current data, it is obvious that exposure to diagnostic levels of

radiation carries little chance for spontaneous abortion, teratogenesis, or growth retardation. The

increased risk of future cancer, however, does exist and must be weighed against the utility of the

information provided by the study.

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Ultrasound

Ultrasonography uses high-frequency, acoustic radiation to create images. A surface transducer

containing piezoelectric crystals converts electrical energy into sound waves. Sound waves pass through

tissue layers and are reflected back to the transducer when they encounter an interface between tissues

of different densities. Digital images generated at 50 to more than 100 frames per second undergo

postprocessing that produces the appearance of real-time imaging. Ultrasonography is considered the

first-line diagnostic imaging modality of the pregnant surgical patient because it is nonionizing, widely

available, portable, and of adequate diagnostic performance. This imaging technique has been used in

obstetrics for more than 50 years without reported fetal damage or harmful effects.61,62

Ultrasonography is, however, a form of energy with effects on tissues through which the waveform

penetrates. The two major mechanisms involved in potentially causing bioeffects are direct, resulting

from the alternation of positive and negative pressures (mechanical or cavitation effects) and indirect,

caused by heating of tissues secondary to transformation of the acoustic energy (thermal effects).

Because of these theoretical concerns, several organizations have recommended that this diagnostic

procedure should be performed only when there is a valid medical indication and the lowest possible

ultrasonic exposure setting under the as low as reasonably achievable principle.63–65

Computed Tomography

In the past 10 years, the use of radiologic examinations in pregnant women has increased by 107%, with

the greatest increase occurring in the use of CT.66 Computed tomography is most valuable in the second

and third trimesters, when ultrasonography is of limited value, in a patient with a large body habitus,

and when MRI is inconclusive or not available.67 Because of its sensitivity for the detection of

abdominal and pelvic injury as well as retroperitoneal injury in which the clinical urgency requires

prompt diagnosis, CT is the test of choice for injured pregnant patients.68–70 When CT is performed

during pregnancy, using dose-reduction protocols (e.g., abdominal and internal barium shielding) results

in significant reduction in the probability of biologic effects to the fetus without sacrificing the

necessary diagnostic image quality.71

Magnetic Resonance Imaging

Like ultrasonography, MRI uses no ionizing radiation, instead relying on the magnetic properties of

tissues to create images. Four magnetic fields interact during an MRI examination to create the image.

The intrinsic magnetic field of an atomic nucleus, usually that of a hydrogen proton, is combined with a

strong, uniformly applied external magnetic field and a weaker magnetic field gradient. In addition, a

magnetic field is intermittently generated by pulsed radio frequency waves.52 When the radio frequency

ceases, the nuclei return to their previous orientation and emit the radio frequency they absorbed. These

signals are detected, stored, and processed by a computer to create an image. Theoretical concerns

include the effects of fluctuating electromagnetic fields and high sound intensity levels with potential

damage to the fetal ear. Other known dangers of MRI exposure include trauma from projection of small

metal fragments into the eyes, interference with the operation of implantable electronic devices,

position of metallic implants, and burns from heating of conductive materials in implants. Despite these

concerns, present data have not conclusively documented any deleterious effects of MRI exposure on the

developing conceptus or the pregnant woman.72

PHYSIOLOGIC CHANGES OF PREGNANCY THAT MIMIC DISEASE

Pregnancy physiology reflects the changes necessary for fetal gestation. It is characterized by the

enlarging, gravid uterus and a changing hormonal milieu. These conditions predispose to certain

diseases and change maternal physiology to mask the diagnosis of others. The cardiovascular system is

affected by pregnancy. The cardiac output increases by 30% to 50%, as does the total blood volume.

The corresponding red blood cell volume increases only by 20% to 30%, leading to a decrease in the

hematocrit. Although the maternal oxygen-carrying capacity is increased and the rheologic properties of

blood are optimized for maximum nutrient delivery to the fetus, a physiologic anemia develops that can

be confused with a pathologic state.73 Diagnosis of anemia due to chronic blood loss, as occurs with

cancers of the gastrointestinal tract, may be delayed as the gradually decreasing hematocrit is attributed

to pregnancy. Other laboratory evaluations can also mask various disease states (Table 106-2). Serum

alkaline phosphatase levels gradually increase because of production of an alkaline phosphatase isozyme

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by the placenta. This does not reflect biliary or bone disease. Albumin levels, commonly used to

measure hepatic synthetic function, decrease, and a relative leukocytosis mimics a systemic infection.

Table 106-2 Change During Pregnancy in Laboratory Values

The gastrointestinal tract undergoes a state of relaxation and decreased smooth muscle activity during

pregnancy. The lower esophageal sphincter tone gradually decreases, as does gastric emptying.

Prolonged small bowel transit time and decreased colonic emptying not only work to maximize nutrient

and water absorption but also contribute to the constipation reported by 38% of pregnant women.74

Although multifactorial, the actions of progesterone have been linked to inhibition of gut smooth

muscle activity both in vitro and in vivo. Because this dose-dependent inhibition can be blocked by

increasing the extracellular concentration of Ca2+, at least in vitro, it is proposed than progesterone

works by limiting the effective Ca2+ available for actin–myosin coupling.75,76 This same mechanism

contributes to uterine relaxation early in pregnancy, decreased intestinal motility, and the concurrent

decrease in gallbladder tone and rate of emptying. With these changes, combined with supersaturation

of bile by cholesterol, pregnancy becomes a lithogenic state.77 These effects of pregnancy are transient

and gallbladder motility and volumes return to normal as early as 2 weeks after pregnancy, but the

gallstones, if formed, may persist. Nausea and vomiting of pregnancy is a common occurrence affecting

between 50% and 90% of all women.78,79 These symptoms rarely extend beyond the first trimester.

Other causes must be investigated if the nausea and vomiting occur later in pregnancy. Abdominal pain,

although often due to a surgical pathologic process, can have many causes. Round ligament pain is

described as an aching, dragging pain more often felt on the right side. It is a common occurrence until

31 weeks of gestation. Pain in the hypochondrium can result from uterine pressure on the lower ribs,

and lower abdominal pain may be psychogenic, related to anxiety about the pregnancy or insecurity

over the social situation.80 It is up to the surgeon to determine the cause of abdominal pain in the

pregnant patient and decide the course of diagnosis and intervention.

APPENDICITIS IN THE PREGNANT PATIENT

6 Acute appendicitis is the most common nonobstetric cause of acute surgical abdomen during

pregnancy.81 Disease is confirmed in 65% to 75% of suspected cases for an incidence of approximately

1:1,500 births.82 Although previous series suggested that the condition had similar incidences for

nonpregnant adults, equal distribution throughout pregnancy,83 and a more common occurrence later in

gestation,84,85 a recent large case-control study indicated a lower incidence than among nonpregnant

individuals, particularly in the third trimester.86 The incidence decreases in the third trimester to 15% to

30% compared to rates ranging from 20% to 60% in the first and second trimesters.87,88 A well-known

fact is that the anatomic and physiologic changes of the gravid state make the diagnosis difficult.

Attributing abdominal pain to other etiologies (e.g., pyelonephritis, false labor, and gastroenteritis),

failure to pursue further investigation, and the physicians’ fear of surgically induced premature labor all

contribute to delayed diagnosis and timely appendectomy in pregnancy. Appendiceal perforation rates

are higher when compared with those from nonpregnant populations (55% vs. 4% to 19%).89 This is

probably explained by confounding variables leading to the delay of diagnosis and therapy. Several

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series have documented a correlation between a delay in the diagnosis and gestational age. In the first

trimester, most diagnoses were made promptly and significant delay in operation with a rate of

perforation of 49% reported for patients presenting in the second trimester and a rate as high as 70%

for those presenting in the third trimester.83,90 Perforated appendicitis presents a greater infectious risk

in the pregnant patient than in the population as a whole. The large uterus interferes with proper

omental migration throughout the abdominal cavity and prevents the walling off of the inflammatory

process. Braxton Hicks contractions disrupt adhesion formation, and the general increase in vascularity

of the abdomen with greater lymphatic drainage allows rapid dissemination of infection. The high

circulatory levels of adrenocorticoids in pregnancy have also been hypothesized to diminish the tissue

inflammatory response and hinder containment of infection.91–93 All of the classic signs and symptoms

of appendicitis are altered by pregnancy (Table 106-3). Anorexia, nausea, and vomiting occur in 58% to

77% of pregnant patients with appendicitis.83,90 Although anorexia, nausea, and vomiting in the first

trimester are common, their occurrence during the second and third trimesters, especially if associated

with abdominal pain, require a thorough investigation. In a classic 1932 study, Baer and colleagues

94

evaluated the migration of the appendix through the duration of pregnancy with barium enemas.

Beginning in the first trimester, the appendix and the cecum are gradually displaced by the uterus and

start a caudal migration out of the pelvis into the upper abdomen. By the third trimester, the

appendiceal tip can abut the gallbladder (Fig. 106-4). The vague, referred epigastric pain due to early

appendiceal obstruction is not changed by this anatomic consideration, but the location of the somatic

pain is. In a large study of pregnant women with proven appendicitis, abdominal pain was present in all

patients. Location of pain in the right lower quadrant, however, was common only early in gestation,

and a portion of patients reported pain in the right upper quadrant. This change in symptomatology is

easily understood if the anatomic changes of the appendix are taken into consideration.83 Both guarding

and rigidity are valuable findings on physical examination but are common only in the first trimester.

Elevation of the abdominal wall from the more laterally placed, upward-directed appendix and the

laxity of the abdominal wall musculature caused by this distention decrease the reliability of these

findings. Only 42.9% of patients in the third trimester are reported to have abdominal spasm and

guarding, compared with 80% during the first trimester.95 Psoas and obturator signs are similarly

obscured as the appendix is moved from its normal location and have not been shown to have clinical

significance. The results of laboratory examinations commonly used to assist in the diagnosis of

appendicitis are also obscured by pregnancy. The physiologic leukocytosis of pregnancy, ranging from

5,000 to 12,000 white blood cells (WBCs)/mL, overlaps that of appendicitis. In one collected series, the

WBC count of pregnant patients with proven appendicitis was not significantly elevated over these

values, and only 25% of patients had a WBC count over 15,000. Most patients (50%) had WBC counts

ranging between 10,000 and 15,000, and 25% had less than 10,000 WBCs/mL.83 Urinalysis is a useful

adjunct in the workup of appendicitis but again presents a dilemma in pregnancy. Urinary tract infection

is common in pregnancy as the enlarging uterus compresses the right ureter. Dilatation and stagnant

flow in the right collecting system can contribute to bacterial overgrowth and infection. Pyuria without

bacteria can also indicate involvement of the right ureter in the appendiceal inflammatory process. The

presence of pyuria and bacteriuria does not rule out appendiceal inflammation because the two

conditions may coexist in 40% of pregnant patients.90 The risk of adverse pregnancy outcomes after

appendectomy during pregnancy has been reported by two large population-based studies. From the

California Inpatient File of 3,133 pregnant women undergoing surgery for suspected appendicitis, the

fetal loss rate was 23%, and it was doubled – 6% versus 11% – with simple versus complicated

disease.96 In the other study, the fetal loss rate within 1 week of the procedure was 22%, particularly

when the surgery was performed after 23 weeks.82 Fortunately, these same researchers noted no

additional increase in the preterm birth rate among the pregnancies that continued beyond the first

postoperative week. Perforated appendicitis in pregnancy rapidly leads to diffuse peritonitis, premature

labor, and fetal loss.85,97

Table 106-3 Variation in Signs and Symptoms of Appendicitis During Pregnancy

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Figure 106-4. Changing location of the appendix throughout gestation.

IMAGING MODALITIES

Ultrasonography is the initial nonionizing imaging modality of choice in these patients. Findings

suggesting appendicitis include visualization of a tubular structure with a diameter of more than 6.0

mm, a wall thickness of more than 3.0 mm, and lack of peristalsis (Fig. 106-5).98,99 One study reviewed

the value of ultrasonography in diagnosing appendicitis in pregnancy. That review reported a range of

sensitivity of 67% to 100% and a range of specificity of 83% to 96%, compared to diagnostic

performance in the general population of 86% and 96%, respectively.100 Ultrasonography, however,

does have limitations due to body habitus, intraluminal air, and operator level of experience. The

examination can also be difficult because of abdominal guarding and pain during examination.

Distortion of anatomic landmarks and the displacement of the appendix by the gravid uterus complicate

the diagnosis. Other structures such as an inflamed salpinx can also mimic appendicitis on

ultrasonogram,101 and a dilated uterine vein during pregnancy has been mistaken for an acutely

inflamed appendix.102 Chest radiography should be considered in the evaluation of patients with

suspected appendicitis because right lower lobe pneumonia may manifest with lower abdominal pain.

Abdominal plain films are usually avoided unless there is suspicion for visceral perforation or bowel

obstruction. Computed tomography has emerged as a highly reliable modality in the diagnosis of

appendicitis. Appendiceal CT, using rectally administered contrast, can be performed within 10 to 20

minutes, does not require a waiting period for oral contrast to progress down through the cecum, and

exposes the patient to only one-third the radiation of a regular CT scan.103 Computed tomography in the

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nonpregnant population is more sensitive and specific than sonography (approximately 98% each) to

confirm suspected appendicitis.104 A computed tomographic scan is considered abnormal if there is an

enlarged appendix (>6 mm in maximum diameter) or if there are periappendiceal inflammatory

changes such as fat stranding, phlegmon, fluid collection, and extraluminal gas. Routine use of this

modality has been shown to reduce costs, expedite the diagnosis, and reduce perforation rates from 22%

to 14% while decreasing the incidence of negative laparotomy from 20% to 7%.105–107 Radiation

exposure is 300 mrad with a limited helical CT scan, which is one-third of the amount of the average

abdominopelvic CT scan.108 Because even low levels of radiation in utero can increase the incidence of

childhood cancer, widespread use of this modality in the pregnant patient with abdominal pain may be

detrimental. Reserving the CT scan for those cases in which the clinical history, physical examination,

and ultrasonography are indeterminate should decrease the rate of perforation and negative exploration,

just as it has in the nonpregnant population (Fig. 106-6). MRI uses nonionizing radiation, has no known

adverse fetal effects, and, like CT, has the potential to image the whole abdomen. On MRI an appendix

is considered abnormal when it is fluid-filled, greater than 6 or 7 mm in diameter, or demonstrates the

presence of periappendiceal inflammatory changes. A study suggested that a normal appendix on MRI

had a high specificity (98% to 100%) and a high negative predictive value (94% to 100%) in excluding

acute appendicitis.109 The American College of Radiology guidance documented MRI safe practices 2013

and reaffirmed its use in pregnancy if considered necessary irrespective of gestational age. Intravenous

gadolinium contrast has no known adverse effects in humans but its use should be based on whether the

potential benefits to the patient exceed the theoretical risks to the fetus.110

Figure 106-5. Ultrasonographic appearance of appendicitis. The appendix appears as a thick, noncompressible tubular structure

with central hypoechogenicity. The walls are 5-mm thick, over the 3-mm limit for a normal appendix. (Courtesy of Dr. Beverly

Coleman, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.)

Laparoscopy

Laparoscopy to evaluate the appendix is a feasible diagnostic modality during pregnancy but may be

difficult during later gestation. Anatomic changes alter placement of trocars above the gravid uterus

111

and require the use of the open Hasson technique of trocar placement under direct visualization rather

than blind insufflation with a Veress needle. Maneuvers to enhance operative safety of laparoscopy in

pregnancy have been outlined by the Society of American Gastrointestinal Endoscopic Surgeons (Table

106-4).112

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Figure 106-6. Computed tomographic (CT) scan of a woman in the 18th week of gestation presenting with a 12-hour history of

right-sided abdominal pain. Abdominal examination on presentation revealed significant tenderness, and after a nondiagnostic

ultrasonography, a laparotomy is considered for presumed appendicitis. A CT scan is obtained instead, revealing a normal, air

filled appendix with no sign of periappendiceal inflammation (arrow). The laparotomy was postponed, and 12 hours later the

patient aborted a septic fetus. An unnecessary laparotomy for an atypical presentation of chorioamnionitis was avoided by the

judicious use of the CT scan. (Courtesy of Dr. David Weiss, Chestnut Hill Hospital, University of Pennsylvania Health System,

Philadelphia, PA.)

Appendectomy

Once the diagnosis of appendicitis is made, treatment is strictly surgical. If an open procedure is chosen,

a muscle splitting incision is made over the point of maximum tenderness because the appendix

customarily lies beneath that point.81,83,90 A right paramedian incision usually necessitates medial

retraction of the uterus for exposure and increases the risk of precipitating premature labor. By tilting

the patient 30 degrees to the left, the uterus is shifted away from the operative field and off the inferior

vena cava. Because of the migration of the appendix, an incision over McBurney point in the late second

and third trimesters is inadequate. If diffuse peritonitis is present, a midline incision is usually

performed. Perforated appendicitis or pus in the abdominal cavity demands thorough peritoneal toilet

along with the appendectomy. A periappendiceal abscess can be treated with percutaneous drainage,

followed by an interval appendectomy 2 to 3 months later.113 Perioperative antibiotics should be

administered to cover gram-negative bacteria and anaerobes, usually a second- or third-generation

cephalosporin, expanded-spectrum penicillin, or even triple agent therapy.114 Unless there is gangrene,

perforation, or a periappendiceal phlegmon, antimicrobial therapy can usually be discontinued after

surgery. Seldom is cesarean delivery recommended at the time of appendectomy. Although uterine

contractions are common, tocolytic therapy is generally not recommended. If exploration reveals a

normal appendix, an appendectomy still should be performed. Although some authors question this

approach because of the suggested high rate of preterm labor with a normal appendectomy,115 most

believe this to be untrue. Taking out the normal appendix adds little to morbidity while eliminating

potential confusion if symptoms should recur.83 Since it was first performed in 1980, laparoscopic

appendectomy in pregnancy has spawned controversy, which continues to this date. Its use in pregnancy

has been recently documented with a good safety record.116 It has a complication rate similar to that for

nonpregnant laparoscopy.117 Its major advantages over open appendectomy include less abdominal wall

trauma, less pain and narcotic use, and faster return to normal activity. However, the presence of the

enlarged uterus does increase the risk of inadvertent puncture with a trocar or Veress needle.118 In the

second half of pregnancy, open laparoscopy may be preferred to avoid such complications. Unlike

nonpregnant laparoscopy, no instrument should be applied to the cervix. The primary trocar is inserted

after determining the size of the uterus, and the secondary trocars are inserted under direct

visualization. Consideration of supraumbilical, subxiphoid insertions may be necessary. Limiting intraabdominal pressures to less than 12 mm Hg and reducing operative time can reduce concerns about

maternal hypercarbia and subsequent fetal acidosis. Laparoscopy is almost always used to treat

suspected appendectomy during the first two trimesters. There were similar perinatal outcomes from

the Swedish database of nearly 2,000 laparoscopic appendectomies compared with those of more 1,500

open laparotomies done before 20 weeks.119 Conversely from their review, Wilasrusmee and

coworkers

120 reported a higher fetal loss with laparoscopy.

Table 106-4 Guidelines for Laparoscopic Surgery during Pregnancy

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BILIARY TRACT DISEASE IN PREGNANCY

7 After appendicitis, acute cholecystitis is the second most common nonobstetrical indication for surgery

in pregnant women and the most common cause of maternal hospitalization in the first year after

delivery.121 Pregnancy and the postpartum period appear to predispose women to gallstone formation.

This is attributed to increase in sex steroid hormone levels in pregnancy, causing biliary stasis,

prolonged intestinal transit, and increased cholesterol saturation of bile. Multiparity and prepregnancy

obesity are the two major independent risk factors for cholelithiasis in pregnancy. One study found that

gallstones occurred in 7% of nulliparous women, with the rate rising to 19% of women with two or

more pregnancies. This risk of gallstones appears to increase during gestation, with sludge or stones

found in 5.1% of 3,254 prospectively studied women in the first trimester, 7.9% in the second trimester,

and 10.4% by 4 to 6 weeks after delivery.122 However, among women with sludge or stone, only 1.2%

developed any symptoms attributable to the gallbladder during pregnancy.123 Despite the predilection

for stone formation in pregnancy, acute cholecystitis does not occur more frequently during pregnancy.

Data suggest that cholecystitis affects only 0.1% of pregnant women.124 Most patients with symptomatic

gallstones present with complaints of biliary colic likely resulting from gallbladder contractions and

increased pressure and luminal expansion characteristically exacerbated by a fatty meal. These patients

often complain of epigastric or right upper quadrant pain. The onset of pain is typically between 1 and 3

hours postprandially. The discomfort progresses in less than an hour to a steady plateau that ranges

from moderate to excruciating and remains constant for more than an hour and then subsides slowly

over several hours. Less frequently, the symptoms are those of one of the complications of gallstones,

acute cholecystitis, cholangitis, or pancreatitis. Signs and symptoms may include right upper quadrant

pain, fever, tachycardia, leukocytosis, anorexia, and vomiting. Sepsis and jaundice may also be seen.

Abdominal examination usually demonstrates voluntary and involuntary guarding and frequently a

positive Murphy sign. Laboratory studies should be normal in patients with uncomplicated

cholelithiasis. However, mild elevations in serum aminotransferases and amylase may occur as a result

of the passage of small stones or sludge. Significant elevations in aminotransferases, hyperamylasemia,

increased direct bilirubin, and alkaline phosphatase may be signs of complicated gallbladder disease.

The differential diagnosis includes appendicitis, pancreatitis, peptic ulcer disease, pyelonephritis, rightsided pneumonia, acute fatty liver of pregnancy, and preeclampsia. Abdominal ultrasound is a reliable

diagnostic tool for identifying gallstones, sludge, and acute or chronic cholecystitis with a high

sensitivity and specificity.125 A diagnosis of acute cholecystitis is suspected by findings of gallbladder

distention, gallbladder wall thickening, and pericholecystic fluid on ultrasonography.126 Transabdominal

ultrasonography is relatively insensitive for the detection of common bile duct stones, whereas

endoscopic ultrasound is highly accurate for that purpose. Magnetic resonance

cholangiopancreatography (MRCP) may be used when extrahepatic ductal stones are suspected or in

complicated cases when ultrasound is nondiagnostic. Endoscopy of the biliary system by endoscopic

retrograde cholangiopancreatography (ERCP), with its associated radiation exposure, can be performed

safely in pregnant patients but should be limited to cases in which treatment of ductal stones is

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required. The appropriate management for symptomatic cholelithiasis and acute cholecystitis during

pregnancy is controversial. Suggested management for a pregnant patient with symptomatic

cholelithiasis during the first trimester consists of conservative measures until elective cholecystectomy

can be performed safely during the second trimester. Traditional supportive care includes withdrawal of

oral food and fluids, pain control, intravenous fluids, and nasogastric aspiration depending upon the

clinical presentation. However, nonoperative management of symptomatic cholelithiasis is associated

with significant recurrence bouts of symptoms, prolonged total parenteral nutrition, higher rates of

preterm delivery, cesarean section, and more technically difficult cholecystectomies compared with

laparoscopic cholecystectomy. 127–129 Cholecystectomy can be performed safely and effectively during

pregnancy in all trimesters. Either an open or laparoscopic approach may be chosen; however,

laparoscopic cholecystectomy is the preferred technique for removal of the gallbladder in pregnant

women. Overall, patients have a shorter postoperative stay, resume oral intake earlier, have fewer

postoperative hernias, and experience less pain with lower narcotic requirements by avoiding a large

open incision.130–132 Because fetal loss is most likely related to the underlying maternal illness and

extent of uterine manipulation during surgery,133,134 laparoscopic cholecystectomy offers a solution to

both problems. Based on the available data, laparoscopic cholecystectomy is safe during pregnancy and

is preferable to open cholecystectomy.135 Removing the diseased gallbladder eliminates the potential for

recurrence, and the minimal uterine retraction needed with laparoscopic access to the right upper

quadrant should decrease the risk for preterm labor. After an open cholecystectomy, the reported rate

of premature labor ranges from 0% to 40%, based on trimester,136 and a spontaneous abortion or

premature birth rate of up to 22% has been reported.137 The incidence of premature uterine contractions

with laparoscopic cholecystectomy has been reported at 0% to 21%, but contractions are usually well

controlled by tocolytics. Most series report rates of premature birth or spontaneous abortion ranging

from 0% to 7% with the laparoscopic approach.111,133,134 The second trimester is the optimal time to

perform an elective cholecystectomy. Organogenesis is complete and the gravid uterus is not yet large

enough to impinge on the operating field.138 Those patients presenting later in gestation can probably

be managed symptomatically until the postpartum period, with cholecystectomy generally performed 6

weeks following delivery to allow the mother to recover and to bond with her infant.

Choledocholithiasis

Indications for evaluation of the common bile duct are no different in the pregnant patient than in the

population as a whole – namely, a bilirubin elevated over 1.5 mg/dL, a dilated common bile duct, or

gallstone pancreatitis.111 ERCP can be performed in pregnancy. With proper lead shielding, judicious

use of fluoroscopy time, and avoidance of permanent roentgenographic films, ERCP has been performed

with no direct exposure of the fetus to radiation. Calculated scatter radiation on the order of 4 mrads

during the whole examination presents the only risk from ionizing radiation.139 Evaluation of the biliary

tree, stone retrieval, and sphincterotomy can be performed under these conditions without maternal or

fetal complications.140 Other methods avoid radiation altogether and include imaging of

choledocholithiasis with endoscopic ultrasonography,141 endoscopic papillotomy under ultrasonographic

control,142 and MRCP for choledocholithiasis.143 Success with all these modalities has been reported but

can be limited by operator experience and availability.

INTESTINAL OBSTRUCTION DURING PREGNANCY

8 The incidence of intestinal obstruction during pregnancy rose throughout the 20th century. In the

presurgical era, cases were cited as infrequently as 1:68,000 deliveries. Since the 1940s, however, the

incidence has increased to 1:2,500 to 3,500 deliveries.144,145 This change reflects the increased number

of pelvic and abdominal surgeries in young women that includes cesarean deliveries.146–148 Adhesions

remain the most common cause of intestinal obstruction in the gravid patient, but intestinal volvulus is

a much more common complication than that in the population as a whole. Intussusception, hernia, and

carcinoma are responsible for a minority of cases of bowel obstruction (Table 106-5). The incidence of

adhesion-related obstruction is highest during the first pregnancy after an operation, when the

association between the viscera and adhesions is initially tested. Most cases of intestinal obstruction

during pregnancy result from pressure of the growing uterus on intestinal adhesions. According to Davis

and Bohon, this likely occurs (1) around midpregnancy, when the uterus becomes an abdominal organ;

(2) in the third trimester, when the fetal head descends; or (3) immediately postpartum, when there is

3133

an acute change in uterine size.144,145

In the general population, incarceration of bowel in groin hernias is the second most common cause

of small bowel obstruction, but in the pregnant patient, volvulus becomes the number 2 cause. Sigmoid

volvulus, the most common site of volvulus during pregnancy, normally occurs owing to a long and

redundant sigmoid colon.149 Anatomic changes of pregnancy further exacerbate this condition by

causing the redundant sigmoid colon to rise out of the pelvis and twist around its point of fixation.150,151

Cecal volvulus occurs because of failure of lateral peritoneal fixation during development. As the uterus

enlarges during pregnancy, it raises the redundant or abnormally mobile cecum out of the pelvis. If a

transition point or distal obstruction should occur from uterine pressure or an adhesive band, the colonic

distention raises the colon even higher, producing torsion around this fixed point.152 Volvulus of the

small bowel can also result from a congenital abnormality of rotation and fixation. The enlarging uterus

potentially predisposes to the presentation of this anomaly during pregnancy by pushing the nonfixed,

mobile portions of the small bowel into the upper abdomen, initiating the volvulus.153,154

Table 106-5 Causes of Intestinal Obstruction Complicating Pregnancy and the

Puerperium in 66 Patients

Presentation and Diagnosis

Perdue149 reported that 98% of pregnant women had either continuous or colicky abdominal pain, and

80% had nausea and vomiting, symptoms that are similar to those in the nonpregnant patient.

Abdominal tenderness was found in 70%, and abnormal bowel sounds noted in only 55%.149 High small

bowel obstruction results in short periods between vomiting episodes with poorly localized, crampy

upper abdominal pain. Colonic obstruction can present with less frequent, feculent vomiting and lower

abdominal pain. Findings on physical examination such as abdominal distention are often difficult to

evaluate because of the gravid uterus. Obstipation, although characteristic of low obstruction such as

that of sigmoid volvulus, may not occur with high obstruction. Laboratory studies, although useful to

rule out other conditions, are not reliable enough to be considered diagnostic of obstruction. Significant

leukocytosis can occur with necrosis and bowel strangulation, but mild elevations are confusing because

of the physiologic leukocytosis of pregnancy. Tachycardia and hypotension are also late signs suggesting

bowel compromise and shock. The murky clinical picture combined with the tendency to treat the

progressive vomiting as a normal part of pregnancy and crampy abdominal pain as early contractions

lead to a delay in presentation and diagnosis. The median time from the onset of symptoms to

admission in one series was 48 hours, and the median time from admission to a necessary laparotomy

was also 48 hours. This delay in diagnosis and treatment contributed to excessive maternal and fetal

mortality.149 Abdominal pain and vomiting in a pregnant patient with an abdominal scar should raise

the serious suspicion of small bowel obstruction. If intestinal obstruction is suspected, upright and flat

films of the abdomen are the diagnostic studies of choice. Serial films obtained every 4 to 6 hours

usually show progressive changes confirming the diagnosis.144 Small bowel obstruction gives the

appearance of a progressive stepladder formation with dilatation and multiple air–fluid levels. Large

bowel obstruction can produce a similar picture or reveal a grossly dilated bowel loop suggestive of

volvulus. Contrast studies are also useful, and a “bird’s bill” shape of contrast with gradual narrowing

after a barium enema can be diagnostic of colonic volvulus, whereas dilute Gastrografin or barium by

mouth can usually differentiate partial from complete obstruction. Fetal radiation risks from the plain

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radiographs are negligible and greatly outweighed by those from the possibility of misdiagnosis.

Because plain radiographs are less accurate for diagnosing small bowel obstruction, CT and MRI can be

diagnostic.155,156 Colonoscopy can be both diagnostic and therapeutic for colonic volvulus.157–160 During

pregnancy, mortality rates with obstruction can be excessive because of difficult and thus delayed

diagnosis, reluctance to operate during pregnancy, and the need for emergency surgery.161,162 Perdue

and Johnson149 described a 6% maternal mortality rate and a 26% fetal mortality rate. Two of the four

women who died were in late pregnancy, and they had sigmoid or cecal volvulus caused by

adhesions.145

Treatment

The initial treatment of bowel obstruction in the pregnant patient is no different from that in a

nonpregnant patient. Nasogastric tube decompression and fluid resuscitation are the cornerstones of

therapy. By the time an obstruction is visible on plain film, the fluid deficit due to vomiting and

intraluminal losses is estimated at 1,000 to 1,500 mL. In advanced cases of dehydration presenting with

tachycardia and hypotension, fluid losses may be as high as 4 to 6 L.144 Prompt fluid resuscitation is

essential in the pregnant patient because compromise of uterine blood flow leads to fetal compromise

and demise. Surgical intervention plays a more prominent and earlier role in the management of the

pregnant patient with bowel obstruction. Although adhesion-related small bowel obstruction in the

nonpregnant patient usually resolves with nasogastric decompression and fluid administration,

numerous series have documented failure of conservative management of small bowel obstruction in the

pregnant woman. Eighty-nine percent to 100% of patients eventually require an operation, and 13% to

23% require resection of gangrenous bowel at the time of laparotomy.151,156 Based on these outcomes,

some have stated that once the diagnosis of small bowel obstruction is made in a pregnant patient, the

only role of nasogastric decompression and fluid resuscitation is to prepare the patient for an

operation.151 Cecal volvulus is also treated surgically, and although sigmoid volvulus in the

nonpregnant patient can be managed with sigmoidoscopic decompression and placement of a rectal

tube, the large gravid uterus may act as a mechanical impediment to detorsion. A laparotomy is usually

necessary for the treatment.145,155 A generous midline incision allows for maximum exposure of the

abdomen with minimal manipulation of the uterus. During lysis of small bowel adhesions, bowel

viability must be carefully assessed. Definitive management of cecal volvulus requires resection of

necrotic cecum or detorsion and cecopexy. Sigmoid volvulus should also be treated by resection if

necrotic but simple detorsion and placement of a rectal tube can be performed if the sigmoid is viable.

Although resection of the redundant sigmoid is the definitive treatment of this disease, it can be delayed

until the postpartum period. Aggressive surgical treatment has been credited with reducing the maternal

and fetal mortality rates from 20% and 50%, respectively, in the 1930s to 6% and 26% today.151

Increased awareness of this disease and expeditious management can reduce those rates even further.

COLORECTAL CANCER DURING PREGNANCY

9 Colorectal cancer is the third most frequent malignancy in women of all age groups in the United

States,161 but it rarely complicates pregnancy because it is uncommon before 40 years of age. The mean

age at diagnosis of colorectal cancer in pregnancy is 31 years (range 16 to 48 years).162 The incidence of

colon cancer was estimated as 1:50,000 pregnancies based on a 1955 report.163 More recent reviews

estimate the incidence as 1:13,000 deliveries,164 with the increasing prevalence of colorectal cancer

diagnosed during gestation due to the current trend of delaying pregnancy into the later reproductive

years.165 The majority of colorectal carcinoma in pregnant women arise from the rectum. This location

is at odds with the pattern seen both in the general population and in nonpregnant patients younger

than 40 years in whom, as reported by the American Cancer Society in 1981, 69% of tumors were in the

colon and 31% in the rectum.166 On reviewing more than 200 published cases of colorectal cancer in

pregnancy, it was noted that 86% occurred below the peritoneal reflection and were thus rectal

tumors.162 The observed deviation from the usual tumor distribution is likely attributed to detection

bias because of the increased frequency of pelvic examinations in the prenatal period or the change in

pelvic anatomy and symptoms of rectal compression by the gravid uterus. Pregnant patients present

with more advanced cancers than the population as a whole. The advanced stage of disease on

presentation most likely results from a delay in the diagnosis and the low clinical suspicion of

malignancy in this population. In a study, no patients were Duke stage A, 41% were stage B, 44% stage

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C, and 15% stage D. In addition, most colorectal cancers are not diagnosed until late in pregnancy (>20

weeks) or at the time of delivery.164 Pregnancy could cause rapid tumor growth and progression of

disease. There is a wide variation in the presence and expression of estrogen and progesterone receptors

in colorectal tumors and, therefore, their biologic significance is unknown.167,168 Colonic malignancy

during gestation most likely represents pregnancy superimposed on colon cancer rather than a

pregnancy-related disease.

Diagnosis

The most frequent symptoms of colorectal cancer are abdominal pain, distention, nausea and vomiting,

constipation, and rectal bleeding. The diagnosis may be delayed because many of the symptoms are

common in pregnancy. Certainly, when a pregnant patient presents with or without rectal bleeding and

persistent signs or symptoms suggestive of colorectal disease, rectal examination, stool tests for occult

blood, and flexible sigmoidoscopy or colonoscopy should be done. Complete colonoscopy, as indicated

for the nonpregnant patient, is the procedure of choice to obtain a biopsy and confirm the diagnosis of

colorectal cancer in pregnancy.169 However, possible adverse effects of colonoscopy in pregnant women

include placental abruption, fetal exposure to potential teratogenic medications, and fetal injury

resulting from maternal hypoxia or hypotension.170 If deemed necessary, both the patient and her

family should be fully informed about the potential risks to the mother and the fetus, and informed

consent should be obtained. Because most cancers are located below the peritoneal reflection, they can

be easily accessed and sampled for biopsy through a limited sigmoidoscopic examination. Endoluminal

ultrasonographic staging of rectal cancer is particularly useful during pregnancy because of its ability to

evaluate invasion of the uterus or encroachment of the cervix that could prevent vaginal delivery.171

Serum carcinoembryonic antigen levels are normal or only marginally elevated in a normal pregnancy.

Therefore, baseline values should be measured and followed and used in the same way as in the

nonpregnant patient.172,173 Although abdominal CT for staging colon cancer in pregnancy is

contraindicated, particularly in the first trimester, it can be performed later in pregnancy in more

difficult and advanced cases. Alternatives include ultrasonography and MRI without contrast to assess

the extent of the cancer in the abdomen and the pelvis. Ultrasonography has a sensitivity of 75% for

detecting hepatic metastases.

Treatment

Treatment of colon cancer in pregnant women involves caring for both the patient and the fetus and

requires a multidisciplinary approach, which may include but is not limited to the obstetrician–

gynecologist, maternal–fetal medicine specialist, colorectal surgeon, medical oncologist, neonatologist,

pharmacist, social worker, and psychological support services. Aside from the difficulty in dealing with

a potentially lethal disease in a young person, there is an inherent conflict between the treatment of the

mother and the fetus. Treatment of colon cancer puts the two at odds. The necessary treatment must

balance oncologic outcomes with the effect on the pregnancy, and decisions regarding the management

of pregnancy include termination, iatrogenic prematurity, or intentional delay in treatment. The

decision-making process must also account for the wishes of the patient/family, tumor stage, gestational

age, and the effects of the specific therapeutic option.174 In addition, tumor complications such as bowel

obstruction, perforation, or bleeding may force surgical intervention.175 Although there are no

universally accepted guidelines for the treatment of colorectal cancer in pregnancy, the general

consensus is that if the patient is diagnosed at less than 20 weeks’ gestation and there is no evidence of

metastatic disease, surgical resection is indicated. Waiting months until adequate fetal maturation for

delivery can allow cancer dissemination and disease progression.171,176 In most cases, a colon resection

can be handled without disturbing the pregnancy, and resection of even low-lying tumors can be

performed before 20 weeks of gestation.177 During the first half of pregnancy, hysterectomy is not

necessary to perform colon or rectal resection, and thus, therapeutic abortion is not mandated.

However, because of the controversial data regarding the risks of such resections to the pregnancy,

termination of pregnancy and resection of the tumor should be one of the discussed management

options. After 20 weeks, resection may be delayed until after fetal viability.178 Although abdominal

procedures with appropriate fetal and maternal monitoring performed late in pregnancy are not

associated with fetal loss, delaying surgery allows fetal maturity of facilitate surgical exposure and

dissection. If the colorectal tumor causes obstruction in the first half of pregnancy, primary resection,

with or without anastomoses, can be performed. Obstructing tumors discovered in the second half of

pregnancy, depending on the size of the uterus, can be treated with primary resection or by proximal

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