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26. Brown, T. C. K., Barker, G. A., Dunlop. M. E. & Loughnan, P. M. The use of complicating pregnancy, a case report. Am. J. Psychiatry 1941; 98: 201“2.
sodium bicarbonate in the treatment of tricyclic antidepressant-induced 54. Sherer, D. M., D™Amico, M. L., Warshal, D. P. et al. Recurrent mild abruptio
arrhythmias. Anaesth. Intensive Care 1973; 1: 203“10. placentae occurring immediately after repeated electroconvulsive therapy in
27. Cooper, D. J. Acidosis and sodium bicarbonate therapy. Australasian pregnancy. Am. J. Obstet. Gynecol. 1991; 165: 652“3.
Anaesthesia 1994, p39“48. Australian and New Zealand College of 55. Balki, M., Castro, C. & Ananthanarayan, C. Status epilepticus after electro-
Anaesthetists. Printed by Bridge Printery, 29“35 Dunning Ave, Rosebury convulsive therapy in a pregnant patient. Int. J. Obstet. Anesth. 2006; 15:
NSW 2018. 325“8.
28. Grimsley, S. R. & Jann, M. W. Paroxetine, sertraline and fluvoxamine: new 56. Klein, D. F. Delineation of two drug-responsive anxiety syndromes.
selective serotonin reuptake inhibitors. Clin. Pharm. 1992; 11: 930“57. Psychopharmacologia 1964; 17: 397“408.
29. Pastuszak, A., Schick-Boschetto, B., Zuber, C. et al. Pregnancy outcome 57. George, D. T., Ladenheim, J. A. & Nutt, D. J. Effect of pregnancy on panic
following first-trimester exposure to fluoxetine (Prozac). J.A.M.A. 1993; attacks. Am. J. Psychiatry 1987; 144: 1078“9.
269: 2246“8. 58. Carey, G. & Gottesman, I. I. Twin and family studies of anxiety, phobic
30. Chambers, C. D., Johnson, K. A., Dick, L. M., Felix, R. J. & Jones, K. L. Birth and obsessive disorders. In Klein, D. F. & Rabkin, J. G. (eds.), Anxiety:
outcomes in pregnant women taking fluoxetine. N. Engl. J. Med. 1996; 335: New Research and Changing Concepts. New York: Raven Press, 1981.
1010“15. 59. Fawcett, J. Suicide risk factors in depressive disorders and in panic disor-
31. Robert, E. Treating depression in pregnancy (editorial). N. Engl. J. Med. ders. J. Clin. Psychiatry 1992; 53: S9“13.
1996; 335: 1056“8. 60. Buigues, J. & Vallejo, J. Therapeutic response to phenelzine in patients with
32. Howard, L. M., Hoffbrand, S., Henshaw, C., Boath, L. & Bradley, E. panic disorder and agoraphobia with panic attacks. J. Clin. Psychiatry 1987;
Antidepressant prevention of postnatal depression. Cochrane Database 48: 55“9.
Syst. Rev. 2005; 2: CD004363. 61. Rosenberg, L., Mitchell, A. A., Parsells, J. L. et al. Lack of relation of oral clefts
33. Altshuler, L. L., Burt, V. K., McMullen, M. & Hendrick, V. Breastfeeding and to diazepam use during pregnancy. N. Engl. J. Med. 1983; 309: 1282“5.
sertraline: a 24-hour analysis. J. Clin. Psychiatry 1995; 56: 243“5. 62. Rubinchik, S. M., Kablinger, A. S. & Gardner, J. S. Medications for panic
34. Hale, A. S. Recent advances in the treatment of depression. Br. J. Hosp. Med. disorder and generalized anxiety disorder during pregnancy. Prim. Care
1996; 55: 183“6. Companion J. Clin. Psychiatry 2005; 7: 100“5.
35. Henry, J. A. Antidepressants and overdoses. Postgrad. Med. J. 1994; 70: S9“12. 63. Spreight, A. N. Floppy infant syndrome and maternal diazepam and/or
36. Corkeron, M. A. Serotonin syndrome “ a potentially fatal complication of nitrazepam. Lancet 1977; 2: 878.
antidepressant therapy. Med. J. Aust. 1995; 163: 481“2. 64. O™Meara, M. E. & Gin, T. Comparison of 0.125% bupivacaine with 0.125%
37. Kallen, B. Neonate characteristics after maternal use of antidepressants in bupivacaine and clonidine as extradural analgesia in the first stage of
late pregnancy. Arch. Pediatr. Adolesc. Med. 2004; 158: 307“8. labour. Br. J. Anaesth. 1993; 71: 651“6.
38. Zeskind, P. S & Stephens, L. E. Maternal selective serotonin reuptake inhibitor 65. Pritchard, D. B. & Harris, B. Aspects of perinatal psychiatric illness. Br. J.
use during pregnancy and newborn behavior. Pediatrics 2004; 113: 368“75. Psychiatry 1996; 169: 555“62.




370
MALIGNANCY AND PREGNANCY
21
Holly A. Muir, Michael Smith, and David R. Gambling




Introduction because there is a current tendency toward delaying childbirth,
breast cancer during pregnancy is expected to become more
Malignancy complicates between 0.02% and 0.10% of all pregnan-
common.4 Two to five percent of all breast cancers present during
cies and in one study cancer diagnosis was associated with 1 in
pregnancy.5,6 One group estimated that 4500 cases are diagnosed
1000 deliveries.1 Pregnancy does not affect the frequency of can-
annually in the USA.7 In women younger than 45 years of age with
cers seen in women of childbearing age. Melanoma may be the
a breast carcinoma, 7.3% are pregnant or lactating.4 The majority
most frequent malignancy seen during pregnancy (1:350), fol-
of breast cancers diagnosed in pregnancy are infiltrating ductal
lowed by cervical cancer (1:2250), Hodgkin lymphoma (1:3000),
carcinoma.
breast cancer (1:7500), ovarian cancer (1:18 000), and leukemia
(1:75 000).2 However, the National Cancer Institute maintains
Signs and symptoms
that breast cancer is the most common cancer seen in pregnant
and postpartum women at 1:3000 pregnancies (www.cancer.gov/
Breast cancer during pregnancy is difficult to diagnose because of
cancertopics/pdq/treatment/breast-cancer-and-pregnancy).
changes to breast tissue during pregnancy. Ninety percent of
In general, the prognosis for pregnant women with malignant
pregnancy-associated breast cancers are diagnosed after self-
lesions is the same, stage for stage, as for nonpregnant women.
examination of a painless mass,5 but diagnosis often is delayed
However, for many reasons, diagnosis of cancer during preg-
as the patient and/or her physician may be uncomfortable with
nancy occurs at more advanced stages of the disease.
breast examination during pregnancy. As a result, women tend to
Typically, during pregnancy, what benefits the mother also
present with more advanced disease.6 Indications for mammo-
benefits the fetus. However, that is not true in the case of the
graphy, core biopsy, and open biopsy are the same for pregnant
pregnant woman with cancer as treating the cancer often means
and nonpregnant women. Mammography has limited sensitivity
compromising the pregnancy. Depending on the type of cancer
in pregnancy because of changes in radiographic density and it
and gestational age at diagnosis, treatment can sometimes be
requires shielding to minimize fetal exposure. Identification of a
delayed until the fetus is either viable or mature. In some cases,
mass is followed with fine-needle aspiration or open biopsy. Fine-
protection of maternal and fetal health are congruent, but when
needle aspiration has a reported sensitivity and specificity of 94%
care of the mother imposes iatrogenic risk to the fetus, the mother
and is widely used to provide a diagnosis.8 Excisional biopsy can
may decide to delay or alter her treatment for the good of the fetus,
be performed under local anesthesia to minimize fetal anesthetic
potentially to her own detriment.
exposure.

Fetal monitoring Treatment
Fetal and uterine monitoring during cancer surgery is controversial.
The treatment plan for a pregnant woman with breast cancer
Though steps can be taken to improve uterine perfusion and fetal
needs to consider the stage of the malignancy and maturity of
oxygenation if they appear compromised during surgery, monitor-
the fetus. For stage I and operable stage II (localized breast can-
ing may be impractical in emergent or urgent situations, and
cer), the treatment of choice in pregnancy is modified radical
requires expertise often not possessed by anesthesia personnel.
mastectomy.5 A second choice is total tumor excision and axillary
Indeed, fetal monitoring has not been documented to improve
node dissection to be followed by whole breast irradiation after
fetal outcome3 and misinterpretation of the fetal tracing could
delivery. Breast-conserving surgery requires an unacceptably
lead to unnecessary or even unsafe interventions. Although uterine
large dose of radiation for the fetus. However, if the cancer is
activity monitoring is not considered a necessity for the intraopera-
diagnosed late in pregnancy, radiation can be delayed until after
tive management of most pregnant surgical patients, preoperative
delivery of the baby.
and postoperative monitoring of uterine activity and fetal heart rate
For stage III and stage IV disease (locally advanced or meta-
is advocated and tocolysis may be used if uterine activity increases.
static breast cancer), chemotherapy and radiation should be con-
sidered in pregnant women as it would for nonpregnant women.
Breast cancer Breast cancer is most often treated in a multimodal fashion utiliz-
ing surgery, radiation, and chemotherapy. During pregnancy,
Epidemiology
when radiation therapy is relatively contraindicated, the other
Breast cancer affects 1 of every 3000“7500 pregnancies.2,4 two modalities need to be adjusted. Chemotherapy has been
Because it is more common in women of advanced age, and used without harm to the fetus. Termination of pregnancy is not


Obstetric Anesthesia and Uncommon Disorders, eds. David R. Gambling, M. Joanne Douglas and Robert S. F. McKay. Published by Cambridge University Press.
# Cambridge University Press 2008.
5 Other disorders


recommended prior to chemotherapy in the second or third following interscalene blockade in patients receiving cispla-
tin,11 and prolonged neuromuscular block from succinylcholine
trimesters.
in patients treated with alkylating chemotherapeutic drugs.12
The National Comprehensive Cancer Network has recently
released practice guidelines for the treatment of breast cancer Breast cancer can metastasize via the bloodstream to affect
during pregnancy (see Figure 21.1).9, virtually any organ of the body. Dissemination most often is
found in the lung, bones, liver, adrenals, brain, and meninges.
Bone pain and pathologic fractures should be considered
Prognosis
when selecting regional anesthesia and during positioning.
Although pregnancy-associated breast cancer is diagnosed Caution must be taken during neuraxial anesthesia due to
more often in advanced stages, patient age and stage-matched the risk of metastatic disease to the spine or unmasking
prognosis is the same as in nonpregnant women.5 The five- symptoms in women with spinal tumors. Obstruction of the
and ten-year survival rates of pregnant women with breast superior vena cava (SVC) by spread of cancer into the media-
cancer are identical to those of nonpregnant women.10 Babies stinum may cause airway obstruction in a pregnant patient
born to women with breast cancer tend to have lower birth with metastases. One parturient with SVC obstruction deliv-
weights.5, ered uneventfully by cesarean section (C/S) under epidural
anesthesia.13
Correction of electrolyte abnormalities, nutrient deficiencies,
Anesthetic implications
anemia, and coagulopathy may be needed. Hepatic or renal dys-
Anesthetic management must take into account the side effects function may influence the choice of anesthetic drugs.
of chemotherapeutic agents, if used (see Table 21.1). Reported Surgical resection for breast tumors has been done successfully
complications include severe diffuse brachial plexus pathology under cervical epidural block, thoracic paravertebral block, and




Figure 21.1 Practice guidelines for the treatment of breast cancer during pregnancy (with permission).




372
Chapter 21


Treatment
Table 21.1 Side effects of chemotherapeutic agents
Women in early pregnancy (<24 weeks™ gestation), with intra-
Nausea and vomiting
epithelial or microinvasive cervical cancer, can be treated with
Diarrhea and constipation
cold knife conization and large loop excision but the risks of
Anemia
preterm labor, low birthweight and cesarean section are
Malnutrition
increased, more so after large loop excision.17
Memory loss
Some physicians consider delaying treatment in women with
Depression of the immune system, infection, and sepsis
early stage cervical cancer. However, these women should receive
Hemorrhage
complete evaluation, including laparoscopic lymphadenectomy,
Secondary neoplasms
before delaying treatment.18
Cardiotoxicity
Although radical hysterectomy has been the usual therapy for
Hepatotoxicity
cervical cancer in pregnancy, one group looked at delaying ther-
Nephrotoxicity
apy in patients with stage Ia or Ib cervical cancer to optimize fetal
Ototoxicity
outcome. The mean diagnosis to therapy interval was 144 days for
those who delayed versus 17 days for those who did not delay
With large tumors, such as large lymphomas, some patients develop
treatment. Fetal outcome was good in the delayed group, and at
tumor lysis syndrome from the rapid breakdown of malignant cells.
two-year follow-up, all patients were tumor free.19
Although prophylaxis is available and is often initiated in patients with
Others have reported a fertility-preserving surgery (abdominal
large tumors, this is a dangerous side effect, which can lead to death if
radical trachelectomy) for young women with cervical cancer
untreated.
during pregnancy.20 There has been at least one case describing
A proportion of patients report fatigue or nonspecific problems,
a successful pregnancy following radical trachelectomy, using
such as inability to concentrate; this is sometimes called post-
ovum donation and in vitro fertilization.21
chemotherapy cognitive impairment.

Specific chemotherapeutic agents are associated with organ-specific
Prognosis
toxicities, including cardiovascular disease (e.g. doxorubicin),
interstitial lung disease (e.g. bleomycin) and occasionally secondary
Comparing 44 pregnant women diagnosed with all stages of cer-
cancer (e.g. MOPP therapy for Hodgkin disease).
vical cancer to matched nonpregnant controls, van der Vange
found similar survival rates (80%) using standard treatment.22

general anesthesia.14 Regional anesthesia may reduce fetal drug
Anesthetic implications
exposure and maternal risks.

Anesthesiologists should consider the effects of treatment
Cervical cancer with chemotherapeutic agents as well as dealing with a patient
who is potentially immunocompromized. Invasive monitoring
Epidemiology
and regional anesthesia should be performed using strict asepsis.
The reported incidence of cervical cancer during pregnancy var- Most patients with stage IV cancer have local extension of tumor
ies depending upon the report. Some authors consider different into the urinary system and may present with renal failure. Patients
degrees of invasiveness while others deem carcinomas after a with advanced disease may be anemic from chronic disease and
recent pregnancy as being pregnancy related. Overall, approxi- malnutrition. However, most patients with early cervical cancer
mately, 0.02% to 0.40% of pregnancies are associated with cervi- will not present any major anesthetic problems. If laparoscopy
cal cancer and 0.5% to 3.0% of invasive cervical cancers are is required, present evidence suggests that laparoscopic surgery
complicated by pregnancy.15, in pregnancy is a safe option. Left uterine displacement, maintain-
ing end-tidal carbon dioxide between 32“34 mmHg and maternal
blood pressures within 20% of baseline, and limiting abdominal
Signs and symptoms
insufflation pressure to 8“15 mmHg are important factors to
remember.23
The presentation of cervical cancer depends on the extent of the
disease. Most women with cervical cancer are asymptomatic and are
diagnosed with abnormal cytology on routine Papanicolaou (Pap)
Ovarian cancer
screening.7 In one study, pregnant patients were 63% more likely to
be diagnosed using Pap smear than nonpregnant matched cases
Epidemiology
who presented with abnormal bleeding.16 The Pap smear may have
higher rates of false positive and negative tests during pregnancy.15 Ovarian malignancies are rare during pregnancy and are asso-
ciated with favorable maternal and neonatal outcomes because
Vaginal bleeding is the most common symptom of carcinoma
most are diagnosed at an early stage.24 Pregnancy and lactation
of the cervix in pregnancy, thus vaginal bleeding during preg-
suspend ovulation and, thus, are protective factors against
nancy requires evaluation of the cervix.



373
5 Other disorders


the development of ovarian malignancy.25 Ovarian cancer can be been performed successfully during pregnancy using epidural,
combined spinal“epidural, and general anesthesia.33,34
divided into three categories: epithelial carcinoma, germ
cell cancer, and stromal cancer. Germ cell cancer, the most com-
mon type of ovarian cancer associated with pregnancy, originates
Endometrial cancer
in cells destined for ovulation (egg cells). In one report an adnexal
mass of !5 cm was diagnosed by ultrasound in 0.05% of deliv- Endometrial cancer and pregnancy are almost always noncom-
eries.26 The majority were dermoid cysts and only 0.0032% of patible. There are only 24 cases of endometrial cancer in preg-
deliveries were associated with an ovarian cancer.26 nancy reported in the literature35 and most were detected during
first trimester abortions. Five cases were associated with a live
fetus and in two of these cases the diagnosis was made four
Signs and symptoms
months postpartum.
Most tumors are found on routine ultrasound, but the patient There are reports of successful pregnancies following conserva-
may present with pain from torsion, rupture, and obstruction of tive hysteroscopic removal of grade 1 endometrial carcinoma,36,37
labor.27 Screening tests include measuring CA125 levels but these but others warn against such conservative management.38
are not particularly sensitive. Elevation of CA125 in the serum is
not specific to ovarian cancer and can be detected in malignancy
Vulvar cancer
of the fallopian tube, peritoneum, cervix, endometrium, breast,
colon, and lung. However, CA125 may also be elevated in many Epidemiology
benign conditions, including pregnancy, endometriosis, ovarian
Vulvar cancer is rare during pregnancy. The usual histologic types
cysts, and cirrhosis. In addition, CA125 is elevated in only 40% to
of vulvar cancer are squamous cell carcinoma followed by mela-
50% of patients with stage I/II ovarian tumors.
noma and verrucous carcinoma. It has been suggested that vulvar
cancer exists as two separate diseases. The first type involves
Treatment human papillomavirus infection, which predisposes the patient
to vulvar cancer. The second type involves abnormal epithelial
In general, women with malignant ovarian tumors should receive
disorders and advanced age. Approximately 5% of vulvar cancer
immediate optimal treatment regardless of the stage of preg-
occurs during pregnancy and recurrence can occur quickly in the
nancy. Nonsuspicious adnexal masses are treated expectantly,
setting of pregnancy.39
but surgical intervention during pregnancy is indicated for large
and/or symptomatic tumors and those that are suspicious of
malignancy on imaging tests.28 Treatment will depend on the
Signs and symptoms
size, type, and stage of the tumor. It may be managed with open
No features are diagnostic of vulvar cancer and diagnosis is
or laparoscopic surgery, with adjuvant chemotherapy. One report
based on biopsy alone. Therefore, biopsy must be performed on
states that irrespective of the stage of ovarian cancer, conservative
any suspicious lesions of the vulva, asymptomatic or sympto-
surgery and adjuvant chemotherapy for women with malignant
matic. Spread to the vulva from a cervical cancer must be ruled
germ cell tumors achieves a favorable outcome in terms of survi-
val and fertility, compared to radical surgery.29 Various chemo- out.
therapeutic agents have been used successfully during
pregnancy in the second and third trimester with minimal fetal
Treatment
toxicity.30,31
Early surgical treatment is mandatory and consists of radical or
modified radical vulvectomy often with bilateral groin dissection
Prognosis
(depending on the original histology).40 Postdelivery radiother-
apy may be required.
Epithelial ovarian cancer has a poor prognosis due mainly to the
fact that 70% of the women are diagnosed at an advanced stage.
In women with distant metastases, the five-year survival rates are
Prognosis
only 10% to 30%. Survival rates for germ cell cancer treated with
oophorectomy and chemotherapy are very good. The prognosis of patients with vulvar cancer is generally good.
The overall five-year survival is 70% and correlates with the stage
of disease and lymph node status.40
Anesthetic implications
Consideration of the impact from chemotherapeutic drugs is
Anesthetic implications
important, especially the association of cisplatin with peripheral
nerve damage and the development of cardiovascular risk fac- Biopsy can be done under local anesthetic with or without intra-
tors.32 In patients with advanced disease, anemia and electrolyte venous (i.v.) sedation. Surgical resection is best performed under
imbalance may be present, and liver function should be evaluated spinal anesthesia and spinal opioids will reduce the severity of
preoperatively. Laparoscopy for resection of adnexal masses has postoperative discomfort.



374
Chapter 21


Head and neck cancers survival rate for mouth cancer is 55%, a statistic that has not
improved in 30 years.
Epidemiology
Thyroid carcinoma is one of the most common head and neck
Anesthetic implications
cancers in women of reproductive age. In one report thyroid
Any patient with a history of head and neck cancer should be
cancer is rated the third most common cancer diagnosed during
pregnancy.41 In a case series of 15 women with differentiated considered as having a possible difficult airway. Radiotherapy
and previous surgery can alter anatomy, tissue compliance,
thyroid carcinoma during pregnancy, 93% were in stage I, 93%
and vascularity, making visualization during direct laryngoscopy
had papillary thyroid carcinoma, and 60% were diagnosed in the
first trimester at the first antenatal visit.42 difficult. Radiation can make tissues friable and care must be
taken during placement of nasal endotracheal tubes, esophageal
Cancers of the larynx, maxilla, oropharyngeal cavity, thyroid,
stethoscopes, and orogastric/nasogastric tubes.
and parathyroid have been reported during pregnancy, but oral
and oropharyngeal cancer is rare in reproductive age females and
accounts for less than 2% of all cancers.43
Central nervous system (CNS) tumors (also see
Chapter 9)
Signs and symptoms Epidemiology
Thyroid nodules are common in adults. Most are benign; how- The incidence of malignant brain tumors complicating preg-
nancy is 3 per 10 000.47 Although rare, brain tumors during preg-
ever, solitary nodules of the thyroid noticed during pregnancy are
approximately three times more likely to be malignant compared nancy carry the potential for maternal and fetal demise. The
with those in nonpregnant women of the same age.44 Symptoms incidence of choriocarcinoma after a term pregnancy is 0.2 per
10 000, with brain metastases occurring in 14“28% of cases.47
may include hoarseness, neck pain, and enlarged lymph nodes.
Oral and nasopharyngeal cancers are diagnosed by biopsy of There is no particular type of primary brain tumor specifically
suspicious lesions and most often present as a chronic nonheal- associated with pregnancy. The distribution of primary CNS
ing wound. Laryngeal cancer may present as chronic cough, tumors in pregnancy is similar to nonpregnant women, with
hoarseness, stridor, or respiratory distress. gliomas representing the majority of symptomatic neoplasms,
followed by meningiomas and acoustic neuromas.48

Treatment and prognosis
Signs and symptoms
In most cases, termination of pregnancy is not recommended.
Symptoms represent a rapidly escalating neurologic crisis and
Thyroidectomy can be performed in the second trimester if the
usually result from increased intracranial pressure (ICP). Head-
diagnosis is made in the first trimester, and deferred until after
ache is the initial presenting symptom in the majority of those
delivery, if the diagnosis is made later. Radioiodine and thyroid-
with brain tumors, and intractable nausea and vomiting may be
stimulating hormone suppression may be required after delivery.
In one report, pregnancy had no effect on mortality.45 Thyroid difficult to differentiate from morning sickness. Gait disturbance,
seizures, urinary incontinence, memory loss, and paralysis have
cancer has a high cure rate with ten-year survival rates for all

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