diversion, followed by curative resection several weeks after delivery. The surgical management of the

patient’s ovaries is controversial. However, due to the high incidence of ovarian metastases in pregnant

patients with colorectal cancer (25%), compared with a 3% to 8% incidence in the general population,

as well as the poor prognosis of metastatic colorectal cancer in the ovaries, the general recommendation

is for bilateral salpingo-oophorectomy at the time of primary tumor resection.179–181 Nesbitt and

coworkers

176 recommend performing bilateral ovarian wedge biopsies with frozen section, and the

ovaries are removed only when there is metastatic ovarian disease or when hysterectomy is indicated

for another reason. Adjuvant chemotherapy or radiation therapy can improve survival of the mother but

is generally contraindicated during pregnancy, especially early in gestation. Adjuvant chemotherapy

conveys a survival advantage to patients with Dukes stage C colon cancer. The classic adjuvant

chemotherapy includes 5-fluorouracil, an antimetabolite that inhibits DNA synthesis. The safety of this

drug during pregnancy is questionable, and evidence of fetal toxicity exists in animal models. Limited

data on the human fetal safety of this drug are available, and it is considered a category D drug during

pregnancy by the FDA. Chemotherapy during the first trimester is usually contraindicated and should be

limited to those patients with Dukes stage C lesions who are willing to accept the risks of fetal

teratogenesis or demise. Chemotherapy during the second and third trimesters is less teratogenic

because of the completion of organogenesis but still carries some risk for the fetus.171,182 Adjuvant

radiation therapy reduces the local recurrence of rectal cancer. Because the most effective dose to

eradicate microscopic disease is on the order of 50 Gy and the fetus cannot be effectively shielded from

pelvic exposure, radiation therapy cannot be safely performed during pregnancy. Therapeutic pelvic

radiation also results in permanent and irreversible female sterility, so the mother considering this form

of therapy must be fully aware of the risks to the current and future pregnancies.171,183 Vaginal delivery

is not contraindicated unless the tumor is obstructing the birth canal or presents a risk of episiotomy

entering the tumor bed. However, vaginal birth is usually avoided because lower rectal lesions may

cause dystocia, or delivery may cause tumor hemorrhage. If a cesarean section is performed for

obstetric reasons or because of tumor impingement on the birth canal, resection can be performed

immediately, but the operation may be technically easier if done as a separate procedure and postponed

for several days. This is especially important with low rectal lesions, in which decreased pelvic

vasculature can facilitate a low anterior or abdominoperineal resection.176 There is no evidence that

pregnancy influences the course of colorectal cancer, and the prognosis appears to be similar than that

for identical stages in nonpregnant patients.184

References

1. Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the concepts and loss of pregnancy. N

Engl J Med 1999;340:1796–1799.

2. Wegienka G, Baird DD. A comparison of recalled date of last menstrual period with prospective

recorded dates. J Womens Health 2005;14:248–252.

3. Verburg BO, Steegers EA, De Ridder M, et al. New charts for ultrasound dating of pregnancy and

assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound

Obstet Gynecol 2008;31:388–396.

4. Robinson HP, Fleming JE. A critical evaluation of “sonar” crown-rump length measurements. Br J

Obstet Gynaecol 1975;82:702–710.

5. Sladkevicius P, Salvedt S, Almstrom H, et al. Ultrasound dating at 12–14 weeks of gestation: a

prospective cross-validation of established dating formulae in in-vitro fertilized pregnancies.

Ultrasound Obstet Gynecol 2005;26:504–511.

6. Moore KL, Persaud TV. The Developing Human. 8th ed. Philadelphia, PA: WB Saunders; 2008.

7. Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the

NICDH Neonatal Research Network. Pediatrics 2010;26:443–456.

8. Gardner MO, Goldstein RL. The clinical use of antenatal corticosteroids. Clin Obstet Gynecol

1995;38:746–754.

9. Carlo WA, McDonald SA, Fanaroff AA, et al. Association of antenatal corticosteroids with mortality

and neurodevelopmental outcomes among infants born at 22 to 25 weeks’ gestation. JAMA

2011;306:2348–2358.

10. Mori R, Kusuda S, Fujimura M; Neonatal Research Network Japan. Antenatal corticosteroids

3137

promote survival of extremely preterm infants born at 22 to 23 weeks of gestation. J Pediatr

2011;159:110–114.e1.

11. Spong CY. Maternal physiology. In: Cunningham FG, Leveno KJ, Bloom SL, et al., eds. Williams

Obstetrics. 24th ed. New York, NY: McGraw-Hill Companies; 2014:46–77.

12. Norwitz ER, Mahendroo M, Lye SJ. Biology of parturition. In: Creasy RK, Resnik R, eds. Maternal–

Fetal Medicine. 7th ed. Philadelphia, PA: WB Saunders; 2014:66–79.

13. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2009. Natl Vital Stat Rep

2010;59(3):1–19.

14. Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet

2008;371:75–84.

15. Volpe JJ. Overview: perinatal and neonatal brain injury. Ment Retard Dev Disabil Res Rev 1997;3:1–

2.

16. Mathews TJ, MacDorman MF. Infant mortality statistics from the 2006 period linked births/infant

death data set. Natl Vital Stat Rep 2010;58(17):1–31.

17. Institute of Medicine. Preterm Birth: Causes Consequences, and Prevention. Washington, DC: The

National Academies Press; 2007.

18. Savitz DA, Blackmore CA, Thorp JM. Epidemiologic characteristics of preterm delivery: etiologic

heterogeneity. Am J Obstet Gynecol 1991;164:467–471.

19. Berkowitz GS, Blackmore-Prince C, Lapinski RH, et al. Risk factors for preterm birth subtypes.

Epidemiology 1998;9:279–285.

20. Romero R, Avila C, Brekus CA, et al. The role of systemic and intrauterine infection in preterm

parturition. Ann NY Acad Sci 1991;622:355–375.

21. Ou CW, Orsino A, Lye S. Expression of connexin-43 and connexin-26 in the rat myometrium during

pregnancy and labor is differentially regulated by mechanical and hormonal signals. Endocrinology

1997;138:5398–5407.

22. American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine

Committee on Obstetric Practice, Society for Maternal-Fetal Medicine. Committee Opinion No. 455.

Magnesium sulfate for anticipated preterm birth for neuroprotection. Obstet Gynecol

2010;115(3):669–671.

23. King JF, Flenady V, Cole S, et al. Cyclo-oxygenase (COX) inhibitors for treating preterm labour.

Cochrane Database Syst Rev 2005(2):CD001992.

24. Anotayanonth S, Subhedar NV, Neilson JP, et al. Beta mimetics for inhibiting preterm labour.

Cochrane Database Syst Rev 2004(4):CD004352.

25. Allen JR, Helling TS, Langefeld M. Intraabdominal surgery during pregnancy. Am J Surg

1989;158:567–569.

26. Hunt MG, Martin JN Jr, Martin RW, et al. Perinatal aspects of abdominal surgery for nonobstetric

disease. Am J Perinatol 1989;6:412–417.

27. Gordon MC, Samuels P. Indomethacin. Clin Obstet Gynecol 1995;38:697–705.

28. Gordon MC, Iams JD. Magnesium sulfate. Clin Obstet Gynecol 1995;38:706–712.

29. U.S. Food and Drug Administration. FDA Drug Safety Communication: New Warning Against Use of

Terbutaline to Treat Preterm Labor. Silver Spring, MD: FDA; 2011.

http://www.fda.gov/drugs/drugsafety/ucm243539.htm. Accessed March 20, 2012.

30. Witter FR, Zimmerman AW, Reichman JP, et al. In utero beta 2 adrenergic agonist exposure and

adverse neurophysiologic and behavioral outcomes. Am J Obstet Gynecol 2009;201:553–559.

31. Ray D, Dyson D. Calcium channel blockers. Clin Obstet Gynecol 1995; 38:713–721.

32. Hill WC. Risks and complications of tocolysis. Clin Obstet Gynecol 1995; 38:725–745.

33. Sood BG, Lulic-Botica M, Holzhausen KA, et al. The risk of necrotizing enterocolitis after

indomethacin tocolysis. Pediatrics 2011;128:e54–e62.

34. Kort B, Katz VL, Watson WJ. The effects of nonobstetric operation during pregnancy. Surg Gynecol

Obstet 1993;177:371–376.

35. Han S, Crowther CA, Moore V. Magnesium maintenance therapy for preventing preterm birth after

threatened preterm labour. Cochrane Database Syst Rev 2010(7):CD000940.

36. Lyell DJ, Pullen KM, Mannan J, et al. Maintenance nifedipine tocolysis compared with placebo: a

3138

randomized controlled trial. Obstet Gynecol 2008;112:1221–1226.

37. Dodd JM, Crowther CA, Dare MR, et al. Oral beta mimetics for maintenance therapy after

threatened preterm labour. Cochrane Database Syst Rev 2006(1):CD003927.

38. Hon EH. The fetal heart rate patterns preceding death in utero. Am J Obstet Gynecol 1959;78(1):47–

56.

39. Paul RH, Suidan AK, Yeh S, et al. Clinical fetal monitoring. VII. The evaluation and significance of

intrapartum baseline FHR variability. Am J Obstet Gynecol 1975;123:206–210.

40. Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal

monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev

2013(5):CD006066.

41. Chen HY, Chauhan SP, Ananth CV, et al. Electronic fetal monitoring and its relationship to neonatal

and infant mortality in the United States. Am J Obstet Gynecol 2011;204(6):491.e1–10.

42. Resnik R. Electronic fetal monitoring: the debate goes on…and on…and on. Obstet Gynecol

2013;121(5):917–918.

43. Martin J, Hamilton BE, Sutton PD, et al. Births: final data for 2002. Natl Vital Stat Rep 2003;52:1–

113.

44. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human

Development workshop report on electronic fetal monitoring: update on definitions, interpretation,

and research guidelines. Obstet Gynecol 2008;112(3):661–666.

45. Miller DA, Paul R. Antepartum–intrapartum monitoring. In: Scott JR, DiSaia PJ, Hammond CB, et

al., eds. Danforth’s Obstetrics and Gynecology. 8th ed. Philadelphia, PA: Lippincott Williams &

Wilkins; 1999:243–255.

46. Kendrick JM, Neiger R. Intraoperative fetal monitoring during nonobstetric anesthesia. J Perinatol

2000;4:276–278.

47. ACOG Committee on Obstetric Practice. Committee Opinion No. 474. Nonobstetric surgery during

pregnancy. Obstet Gynecol 2011;117(2, pt 1):420–421.

48. Otake M, Schull WJ, Yoshimaru H. A review of forty-five year study of Hiroshima and Nagasaki

atomic bomb survivors. Brain damage among the prenatally exposed. J Radiat Res 1991;32:249.

49. Wertelecki W. Malformations in a Chernobyl-impacted region. Pediatrics 2010;125:e836.

50. Groen RS, Bae JY, Lim KJ. Fear of the unknown: ionizing radiation exposure during pregnancy. Am

J Obstet Gynecol 2012;206(6):456–462.

51. Harrison JD, Stather JW. The assessment of doses and effects from intakes of radioactive particles.

J Anat 1996;189(pt 3):521–530.

52. Wagner LK, Lester RG, Saldana LR. Exposure of the Pregnant Patient to Diagnostic Radiation. Madison,

WI: Medical Physics Publishing; 1997.

53. Brent RL. Saving lives and changing family histories: appropriate counseling of pregnant women

and men and women of reproductive age, concerning the risks of diagnostic radiation exposures

during and before pregnancy. Am J Obstet Gynecol 2009;200:4–24.

54. Donnely EH, Smith JM, Farfan EB, et al. Prenatal radiation exposure: background material for

counseling pregnant patients following exposure to radiation. Disaster Med Public Health Prep

2011;5:62–68.

55. Brent RL. Radiation teratogenesis. Teratology 1980;21:281–298.

56. Brent RL. The effects of embryonic and fetal exposure to x-ray, microwaves, and ultrasound:

counseling the pregnant and non-pregnant patient about these risks. Semin Oncol 1989;16:347–368.

57. Brent RL. The effects of embryonic and fetal exposure to x-ray, microwaves, and ultrasound. Clin

Perinatol 1986;13:615–649.

58. Wood JW, Johnson KG, Omori Y, et al. Mental retardation in children exposed in utero to the

atomic bombs in Hiroshima and Nagasaki. Am J Public Health 1967;57:1381–1390.

59. Wood JW, Keehan RJ, Kawamoto S, et al. The growth and development of children exposed in

utero to the atomic bombs in Hiroshima and Nagasaki. Am J Public Health 1967;57:1374–1380.

60. Harvey EB, Boice JD, Honeyman M, et al. Prenatal x-ray exposure and childhood cancer in twins. N

Engl J Med 1985;312:541–545.

61. Doll R, Wakeford R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997;70:130–139.

3139

62. American College of Obstetrician and Gynecologists. Ultrasonography in pregnancy. ACOG Practice

Bulletin no. 101. Obstet Gynecol 2009; 113:451–461.

63. Marinac-Dabic D, Krulewitch CJ, Moor RM Jr. The safety of prenatal ultrasound exposure in human

studies. Epidemiology 2002;13(suppl 3):S19–S22.

64. American Institute of Ultrasound in Medicine. AIUM practice guideline for the performance of

obstetric ultrasound examinations. J Ultrasound Med 2013;32:1083–1101.

65. Sheiner E, Freeman J, Abramowicz JS. Acoustic output as measured by mechanical and thermal

indices during routine obstetric ultrasound examinations. J Ultrasound Med 2005;24:1665–1670.

66. Reddy UM, Abuhamad AZ, Levine D, et al.; Fetal Imaging Workshop Invited Participants. Fetal

Imaging: Executive Summary of a Joint Eunice Kennedy Shriver national Institute of Child Health

and Human Development, Society for Maternal-Fetal Medicine, American Institute of Ultrasound in

Medicine, American College of Obstetricians and Gynecologists, American College of Radiology,

Society for Pediatric Radiology, and Society of Radiologists in Ultrasound Fetal Imaging Workshop.

Am J Obstet Gynecol 2014;210(5):387–397.

67. Lazarus E, Debenedectis C, North D, et al. Utilization imaging in pregnant patients: 10-year review

of 5270 examinations in 3285 patients—1997–2006. Radiology 2009;251(2):517–524.

68. Leite NP, Pereira JM, Cuhna R, et al. Imaging techniques and diagnostic findings. AJR Am J

Roentgenol 2007;185:407–417.

69. Lowdermilk C, Gavant ML, Qaisi W, et al. Screening helical CT for evaluation of blunt traumatic

injury in the pregnant patient. Radiographics 1999;19:S243–S255.

70. Goldman SM, Wagner LK. Radiologic ABCs of maternal and fetal survival after trauma: when

minutes may count. Radiographics 1999;19:1349–1357.

71. Yousefzadeh D, Ward D, Reft C. Internal barium shielding to minimize fetal irradiation in a spiral

chest CT: a phantom simulation experiment. Radiology 2006;239:751–758.

72. Dewilde JP, Rivers AW, Price DL. A review of the current use of magnetic resonance imaging in

pregnancy and safety implications for the fetus. Prog Biophys Mol Biol 2005;87(2–3):335–353.

73. Martin C, Varner MW. Physiologic changes in pregnancy: surgical implications. Clin Obstet Gynecol

1994;37:241–255.

74. Bonapace ES, Fisher RS. Constipation and diarrhea in pregnancy. Gastroenterol Clin North Am

1998;27:197–211.

75. Gill RC, Bowes KL, Kingma YJ. Effects of progesterone on canine colonic smooth muscle.

Gastroenterology 1985;88:1941–1947.

76. Katz PO, Castell DO. Gastroesophageal reflux during pregnancy. Gastroenterol Clin North Am

1998;27:153–167.

77. Everson GT, McKinley C, Lawson M, et al. Gallbladder function in the human female: effect of the

ovulatory cycle, pregnancy, and contraceptive steroids. Gastroenterology 1982;82:711–719.

78. Broussard CN, Richter JE. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am

1998;27:123–151.

79. Abel TL, Riely CA. Hyperemesis gravidum. Gastroenterol Clin North Am 1992;21:835–849.

80. Baker PN, Madeley RJ, Symonds EM. Abdominal pain of unknown aetiology in pregnancy. Br J

Obstet Gynaecol 1989;96:688–691.

81. Tamir IL, Bongard FS, Klein SR. Acute appendicitis in the pregnant patient. Am J Surg

1990;160:571–576.

82. Mazze RI, Kallen B. Appendectomy during pregnancy: a Swedish registry study of 778 cases. Obstet

Gynecol 1991;77:835–840.

83. Babaknia A, Parsa H, Woodruff JD. Appendicitis during pregnancy. Obstet Gynecol 1977;50:40–44.

84. Al-Mulhim AA. Acute appendicitis in pregnancy. A review of 52 cases. Int Surg 1996;81:295–297.

85. Masters K, Levine BA, Gaskill HV, et al. Diagnosing appendicitis during pregnancy. Am J Surg

1984;148:768–771.

86. Anderson B, Nielsen TF. Appendicitis in pregnancy: diagnosis, management and complications. Acta

Obstet Gynecol Scand 1999;78:758–762.

87. Hee P, Viktrup L. The diagnosis of appendicitis during pregnancy and maternal and fetal outcome

after appendectomy. Int J Gynaecol Obstet 1999;65:129–135.

3140

88. Tracey M, Fletcher HS. Appendicitis in pregnancy. Am Surg 2000;66:555–559.

89. Hale DA, Molloy M, Pearl RH, et al. Appendectomy: a contemporary appraisal. Ann Surg

1997;225:252–261.

90. Weingold AB. Appendicitis in pregnancy. Clin Obstet Gynecol 1983;26:801–809.

91. Black WP. Acute appendicitis in pregnancy. Br Med J 1960;1:1938–1941.

92. Parker RB. Acute appendicitis in late pregnancy. Lancet 1954;266:1252–1257.

93. Wagner JM, McKinney WP, Carpenter JL. Does this patient have appendicitis? JAMA

1996;276:1589–1594.

94. Baer JL, Reis RA, Arens RA. Appendicitis in pregnancy. JAMA 1932; 98:1359–1364.

95. Schwerk WB, Wichtrup B, Rothmund M, et al. Ultrasonography in the diagnosis of acute

appendicitis: a prospective study. Gastroenterology 1989;97:630–639.

96. McGory ML, Zingmond DS, Tillou A, et al. Negative appendectomy in pregnant women is

associated with a substantial risk of fetal loss. J Am Coll Surg 2007;205(4):534–540.

97. Horowitz MD, Gomez GA, Santiesteban R, et al. Acute appendicitis during pregnancy. Diagnosis and

management. Arch Surg 1985;120:1362–1367.

98. Worrell JA, Drolshagen LF, Kelly TC, et al. Graded compression ultrasound in the diagnosis of

appendicitis: a comparison of diagnostic criteria. J Ultrasound Med 1990;9:145–150.

99. Freeland M. Diagnosis of appendicitis in pregnancy. Am J Surg 2009; 198(6):753–758.

100. Williams R, Shaw J. Ultrasound scanning in the diagnosis of acute appendicitis in pregnancy. Emerg

Med J 2007;24:359–360.

101. Paulman AA, Huebner DM, Forrest TS. Sonography in the diagnosis of acute appendicitis. Am Fam

Physician 1991;44:465–468.

102. Abu-Yousef MM, Phillips ME, Franken EA, et al. Sonography of acute appendicitis: a critical

review. Crit Rev Diagn Imaging 1989;29:381–408.

103. Rao PM, Rhea JT, Novelline RA, et al. Helical CT combined with contrast material administered

only through the colon for imaging of suspected appendicitis. AJR Am J Roentgenol 1997;169:1275–

1280.

104. Katz DS, Klein MA, Ganson G, et al. Imaging of abdominal pain in pregnancy. Radiol Clin North Am

2012;50(1):149–171.

105. Rao PM, Rhea JT, Novelline RA, et al. Effect of computed tomography of the appendix on

treatment of patients and use of hospital resources. N Engl J Med 1998;338:141–146.

106. Rao PM, Rhea JT, Rattner DW, et al. Introduction of appendiceal CT impact on negative

appendectomy and appendiceal perforation rates. Ann Surg 1999;229:344–349.

107. Raman SS, Osuagwu FC, Kadell B, et al. Effect of CT on false-positive diagnosis of appendicitis and

perforation. N Engl J Med 2008;358:972–973.

108. Ames CM, Shipp TD, Castro EE, et al. The use of helical computed tomography in pregnancy for the

diagnosis of acute appendicitis. Am J Obstet Gynecol 2001;184:954–957.

109. Long SS. Imaging strategies for right lower quadrant pain in pregnancy. AJR Am J Roentgenol

2011;196(1):4–12.

110. Kanal E, Barcovich AJ, Bell C, et al. ACR guidance document on MR safety practices: 2013. Expert

Panel on MR Safety. J Magn Reson Imaging 2013;37(3):501–530.

111. Gurbuz AT, Peetz ME. The acute abdomen in the pregnant patient. Surg Endosc 1997;11:98–102.

112. SAGES Committee on Standards Practice. Guidelines for laparoscopic surgery during pregnancy.

Surg Endosc 2011;25:2479–3492.

113. Malangoni MA. Gastrointestinal surgery and pregnancy. Gastroenterol Clin North Am 2003;32:181–

200.

114. Vissers RJ, Lennarz WB. Pitfalls in appendicitis. Emerg Med Clin North Am 2010;28(1):103–118, viii.

115. Saunders P, Milton PJ. Laparotomy during pregnancy: an assessment of diagnostic accuracy and

fetal wastage. Br Med J 1973;3:165–167.

116. Sadot E, Telem DA, Arora M, et al. Laparoscopy: a safe approach to appendicitis during pregnancy.

Surg Endosc 2010;24:383–389.

117. Fatum M, Rojansky N. Laparoscopic surgery during pregnancy. Obstet Gynecol Surv 2001;56:50–59.

3141

118. Friedman JD, Ramsey PS, Ramin KD, et al. Pneumoamnion and pregnancy loss after secondtrimester laparoscopic surgery. Obstet Gynecol 2002;99:512–513.

119. Reedy MB, Kallen B, Kuel TJ. Laparoscopy during pregnancy: laparoscopy during pregnancy: a

study of five fetal outcome parameters with use of the Swedish Health Registry. Am J Obstet

Gynecol 1997;177(3):673–679.

120. Wilasrusmee C, Sukrat B, McEvoy M, et al. Systematic review and meta-analysis of safety

laparoscopic versus open appendicectomy for suspected appendicitis in pregnancy. Br J Surg

2012;99(11):1470–1478.

121. Ko CW. Risk factors for gallstone-related hospitalization during pregnancy and the postpartum. Am

J Gastroenterol 2006;101(10):2263–2268.

122. 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(1):39–48.

123. Ko CW, Beresford SA, Schulte SJ, et al. Incidence, natural history, and risks factors for biliary

sludge and stones during pregnancy. Hepatology 2005;41:359–365.

124. Dietrich CS, Hill CC, Hueman M. Surgical diseases presenting in pregnancy. Surg Clin North Am

2008;88:408–419.

125. Boregowda G, Shehata HA. Gastrointestinal and liver disease in pregnancy. Best Pract Res Clin Obstet

Gynaecol 2013;27(6):835–853.

126. Epstein FB. Acute abdominal pain in pregnancy. Emerg Med Clin North Am 1994;12:151–165.

127. Lu EJ, Curet MJ, El-Sayet YY, et al. Medical versus surgical management of biliary tract disease in

pregnancy. Am J Surg 2004;188:755–759.

128. Othman MO, Stone E, Hashimi M. Conservative management of cholelithiasis and its complications

in pregnancy is associated with recurrent symptoms and more emergency department visits.

Gastrointest Endosc 2012;76:564–569.

129. Duphar R, Smaldone GM, Hamad GC. Is there a benefit of delaying cholecystectomy for

symptomatic gallbladder disease during pregnancy? Surg Endosc 2010;24(1):108–112.

130. Conron RW, Abbruzzi K, Cochrane SO, et al. Laparoscopic procedures in pregnancy. Am Surg

1998;65:259–263.

131. Curet MJ, Allen D, Josloff RK, et al. Laparoscopy during pregnancy. Arch Surg 1996;131:546–551.

132. Pucci RO, Seed RW. Case report of laparoscopic cholecystectomy in the third trimester of

pregnancy. Am J Obstet Gynecol 1991;165:401–402.

133. Graham G, Baxi L, Tharakan T. Laparoscopic cholecystectomy during pregnancy: a case series and

review of the literature. Obstet Gynecol Surv 1998;53:566–574.

134. Elerding SC. Laparoscopic cholecystectomy in pregnancy. Am J Surg 1993; 165:625–627.

135. McKellar DP, Anderson CT, Boynton CJ, et al. Cholecystectomy during pregnancy without fetal

loss. Surg Gynecol Obstet 1992;174:465–468.

136. Steinbrook RA, Brooks DC, Datta S. Laparoscopic cholecystectomy during pregnancy review of

anesthetic management: surgical considerations. Surg Endosc 1996;10(5):511–515.

137. McLean M, Bisits A, Davies J, et al. A placental clock controlling the length of human pregnancy.

Nat Med 1995;1:460–463.

138. Printen KJ, Ott RA. Cholecystectomy during pregnancy. Am Surg 1978;44:432–434.

139. Baillie J, Cairns SR, Cotton PB. Endoscopic management of choledocholithiasis during pregnancy.

Surgery 1990;171(1):1–4.

140. Axelrad AM, Fleischer DE, Strack LL, et al. Performance of ERCP for symptomatic

choledocholithiasis during pregnancy: techniques to increase safety and improve patient

management. Am J Gastroenterol 1994;89:109–112.

141. Amouyal P, Amouyal G, Levy P, et al. Diagnosis of choledocholithiasis by endoscopic

ultrasonography. Gastroenterology 1994;106:1062–1067.

142. Parada AA, Goncalves MO, Tafner E, et al. Endoscopic papillotomy under ultra- sonographic

control. Int Surg 1991;76(2):75–76.

143. Yu-leung C, Chan AC, Lam WW, et al. Choledocholithiasis: comparison of MR cholangiography and

endoscopic retrograde cholangiography. Radiology 1996;200:85–89.

3142

144. Davis MR, Bohon CJ. Intestinal obstruction in pregnancy. Clin Obstet Gynecol 1983;26(4):832–842.

145. Hill LM, Symmonds RE. Small bowel obstruction in pregnancy: a report and review of four cases.

Obstet Gynecol 1976;49:170–173.

146. Unal A, Sayherman SE, Ozel L, et al. Acute abdomen in pregnancy requiring surgical management:

a 20-case series. Eur J Obstet Gynecol Reprod Biol 2011;159(1):87–90.

147. Andolf E, Thorsell M, Kaken K. Cesarean delivery and risk for postoperative adhesions and

intestinal obstruction: a nested case-control study of the Swedish Medical Birth Registry. Am J

Obstet Gynecol 2010;203(4):406. e1–e6.

148. Lyell DJ. Adhesions and postoperative complications of repeat cesarean delivery. Am J Obstet

Gyencol 2011;205(suppl 6):S11–S18.

149. Perdue PW, Johnson HW Jr, Stafford PW. Intestinal obstruction complicating pregnancy. Am J Surg

1992;164(4):384–388.

150. Lord SA, Boswell WC, Hungerpiller JC. Sigmoid volvulus in pregnancy. Am Surg 1996;62:380–382.

151. Kantor HM. Midgut volvulus in pregnancy: a case report. J Reprod Med 1990;35:577–580.

152. Pratt AT, Donaldson RC, Evertson LR, et al. Cecal volvulus in pregnancy. Obstet Gynecol

1981;57:37S–40S.

153. Rothstein RD, Rombeau JL. Intestinal malrotation during pregnancy. Obstet Gynecol 1993;81:817–

819.

154. Meyerson S, Holtz T, Ehrinpresis M, et al. Small bowel obstruction in pregnancy. Am J Gastroenterol

1995;90(2):299–302.

155. Essilfie P, Hussain M, Stokes IM. Small bowel infarction secondary to volvulus during pregnancy. J

Reprod Med 2007;52(6):553–554.

156. Biswas S, Gray KD, Cotton BA. Intestinal obstruction in pregnancy: a case of small bowel volvulus

and review of the literature. Am Surg 2006; 72(12):1218–1221.

157. Dray X, Hamzi L, Lo Dico R, et al. Endoscopic reduction of a volvulus of the sigmoid colon in a

pregnant woman. Dig Liver Dis 2012;44(5):447.

158. Khan MR, Ur Rehman S. Sigmoid volvulus in pregnancy and puerperium: surgical and obstetric

catastrophe. Report of the case and review of the growth literature. World J Emerg Surg

2012;7(1):10.

159. Firstenberg MS, Malangoni MA. Gastrointestinal surgery during pregnancy. Gastroenterol Clin North

Am 1998;27(1):73–88.

160. Shiu LH, Rafi J, Corder A, et al. Mid-gut volvulus and mesenteric vessel thrombosis in pregnancy:

case report and literature review. Arch Gynecol Obstet 2011;183(suppl 1):39–43.

161. American Cancer Society. Cancer facts and figures 2013.

http://www.cancer.org/acs/groups/content/@epidemiologysurveillance/documents/document/acspc031941.pdf. Accessed September 6, 2014.

162. Bernstein MA, Madoff RD, Caushaj PF. Colon and rectal cancer in pregnancy. Dis Colon Rectum

1993;36:172–178.

163. McLean DW, Arminski TC, Bradley GT. Management of primary carcinoma of the rectum diagnosed

during pregnancy. Am J Surg 1955;90:816–825.

164. Woods JB, Martin JN Jr, Ingram FH, et al. Pregnancy complicated by carcinoma of the colon above

the rectum. Am J Perinatol 1992;9:102–110.

165. Antonelli NM, Dotters DJ, Katz VL, et al. Cancer in pregnancy: a review of the literature, part 1.

Obstet Gynecol Surv 1996;51:125–142.

166. Silverberg E. Cancer Statistics. New York, NY: American Cancer Society; 1981.

167. Meggouh F, Lointier P, Pezet D, et al. Status of sex steroid hormone receptors in large bowel

cancer. Cancer 1991;67:1964–1970.

168. Francavilla A, Leo D, Polimeno L, et al. Nuclear and cytosolic estrogen receptors in human colon

carcinoma and in surrounding noncancerous colonic tissue. Gastroenterology 1987;93:1301–1306.

169. Girard RM, Lamarche J, Baillot R. Carcinoma of the colon associated with pregnancy. Dis Colon

Rectum 1981;24:473–475.

170. Cappell MS. Colon cancer during pregnancy. Gastroenterol Clin North Am 2003;32:341–383.

171. Cappell MS. Colon cancer during pregnancy: the gastroenterologist’s perspective. Gastroenterol Clin

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North Am 1998;7:225–256.

172. Lamerz R, Ruider H. Significance of CEA determinations in patients with cancer of the colonrectum, and the mammary gland comparison to physiological states in connection with pregnancy.

Bull Cancer 1976;63:575–586.

173. McCall JL, Black RB, Rich CA, et al. The value of serum carcinoembryonic antigen in predicting

recurrent disease following curative resection of colorectal cancer. Dis Colon Rectum 1994;37:875–

881.

174. Salani R, Billingsley CC, Crafton SM. Cancer in pregnancy: an overview for obstetricians and

gynecologists. Am J Obstet Gynecol 2014;211(1):7–14.

175. Minter A, Malik R, Ledbetter L, et al. Colon cancer in pregnancy. Cancer Control 2005;12(3):196–

202.

176. Nesbitt JC, Moise KJ, Sawyers JL. Colorectal carcinoma in pregnancy. Arch Surg 1985;120:636–640.

177. Wobbes T, Beex LV, Koenders AM. Estrogen and progestin receptors in colonic cancer? Dis Colon

Rectum 1984;27(9):591–592.

178. Walsh C, Fazio VW. Cancer of the colon, rectum, and anus during pregnancy: the surgeon’s

perspective. Gastroenterol Clin North Am 1998;27:257–267.

179. Mason MH III, Kovalcik PJ. Ovarian metastases from colon carcinoma. J Surg Oncol 1981;17:33–38.

180. Pitluk H, Poticha SM. Carcinoma of the colon and rectum in patients less than 40 years of age. Surg

Gynecol Obstet 1983;157:335–337.

181. Gurbuz A, Kir G, Karateke A, et al. Metastatic ovarian carcinoma one year after surgical removal of

colon carcinoma during pregnancy: a case report. Int J Gynecol Cancer 2006;16(suppl 1):330–333.

182. Zemlickis D, Lishner M, Degendorfer P, et al. Fetal outcome after in utero exposure to cancer

chemotherapy. Arch Intern Med 1992;152:573–576.

183. Mayr NA, Wen B-C, Saw CB. Radiation therapy during pregnancy. Obstet Gynecol Clin North Am

1998;25:301–321.

184. Dahling MT, Xing G, Cress R, et al. Pregnancy-associated colon and rectal cancer: perinatal and

cancer outcomes. J Matern Fetal Neonatal Med 2009;22(3):204–211.

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SECTION O: SKIN AND SOFT TISSUE

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Chapter 107

Cutaneous Neoplasms

Michael S. Sabel, Timothy M. Johnson, and Christopher K. Bichakjian

Key Points

1 Cutaneous neoplasms are the most commonly diagnosed malignant tumors in the United States.

2 Risk factors for development of cutaneous melanoma include ultraviolet (UV) light exposure, fair

complexion/inability to tan, blue or green eyes, blonde or red hair, freckling, history of actinic

keratosis or nonmelanoma skin cancer (NMSC), history of blistering or peeling sunburns,

immunosuppression, personal or family history of melanoma, CDKN2A/p16/MC1R mutation,

xeroderma pigmentosa, atypical (dysplastic) nevus, more than 100 normal nevi, and giant congenital

melanocytic nevus.

3 The ABCD rule is used to assess skin lesions for melanoma risk: A is for asymmetry; B is border

irregularity; C is color; and D is difference, or a change in a lesion.

4 Melanoma prognosis is inversely correlated to tumor thickness; ulceration and increased mitotic rate

are independent survival risk factors; and nodal tumor burden (uninvolved vs. microscopic vs.

macroscopic disease) has an inverse correlation with survival.

5 For melanoma in situ, excision margins of 0.5 to 1.0 cm are indicated; for invasive melanoma, wide

excision of the primary tumor with margins generally ranging from 1 to 2 cm is indicated for local

control.

6 Clinically involved lymph nodes should be resected; patients with primary melanomas of 1-mm

thickness or greater and clinically negative nodes should be considered for sentinel lymph node

biopsy. Patients with primary melanoma 0.75- to 0.99-mm thickness should also be considered for

sentinel lymph node biopsy if they have additional risk factors for nodal metastases.

7 Basal cell and squamous cell skin carcinoma account for 96% of new NMSCs.

8 Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma treated by a

combination of surgery and radiation, which has a higher mortality than melanoma.

9 Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma (1% of all soft tissue

sarcomas) with a propensity for local recurrence rather than systemic metastasis.

1 Cutaneous neoplasms are the most commonly diagnosed malignant tumors in the United States, with

an incidence of approximately 1.4 million new cases annually.1,2 One in five Americans (one in three

Caucasians) born today will be diagnosed with skin cancer in their lifetime. More than half of all

cancers diagnosed in the United States are skin cancers. The most common skin cancer types are basal

cell carcinoma (BCC) and squamous cell carcinoma (SCC). Cutaneous melanoma accounts for <2% of

skin cancer diagnoses but the vast majority of skin cancer deaths, with 9,940 deaths due to melanoma in

2015. One person dies of melanoma every hour. Approximately 73,870 new cases of invasive melanoma

(42,670 men and 31,200 women) were diagnosed in the United States in 2015. The incidence of

melanoma has dramatically increased, with the lifetime risk of melanoma increasing from 1 in 600 in

the 1960s to 1 in 50 in 2015. Of the seven most common cancers in the United States, melanoma is the

only one whose incidence is increasing. Invasive melanoma is the fifth most common cancer in men and

the seventh most common cancer in women.1 The early diagnosis and surgical treatment of these skin

cancers can be curative.

MELANOMA

Etiology and Risk Factors

2 Numerous environmental and genetic risk factors have been implicated in the development of

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cutaneous melanoma, many of which center around sun exposure.3 Risk factors include factors related

to exposure to UVA and UVB, such as geography, occupation, a history of blistering or peeling sunburns,

and the use of tanning beds/salons, as well as factors related to increased sensitivity to UV light, such as

decreased pigmentation, a fair complexion (blue or green eyes, blonde hair, freckling), or xeroderma

pigmentosa. Melanoma incidence is subject to large geographic and ethnic variations, mainly because of

an inverse correlation with latitude and with degree of skin pigmentation. Populations residing closer to

the equator have a higher incidence of melanoma. Many factors that increase risk for melanoma are

surrogates for a history of excess sun exposure, such as actinic keratosis, a history of either melanoma

or an NMSC, atypical nevi, or multiple normal nevi. Finally, there are inheritable risk factors, such as a

family history of melanoma, CDKN2A/p16 mutation, or MC1R mutation.

Adults with more than 100 clinically normal-appearing nevi, children with more than 50 clinically

normal-appearing nevi, and any patient with atypical or dysplastic nevi are at risk. A prior history of

melanoma places a patient at increased risk, with 5% to 10% of individuals developing a second

primary melanoma. This risk of developing a second primary is lifelong and can occur anywhere on the

skin. Therefore, long-term surveillance with a thorough total body examination is recommended.

A genetic component has been implicated in the pathogenesis of melanoma. Of patients with

melanoma, 10% to 15% report a positive family history. The most common chromosomal mutation

associated with melanoma involves CDKN2A, also known as p16. However, the mutation accounts for

only a small percentage of melanoma cases observed, estimated at 0.2%. An MC1R gene mutation is

clearly a risk factor for cutaneous melanoma.4 The combination of MC1R mutation and red hair is

associated with a very high risk of melanoma development. In addition, MC1R R151 C modifies the

effect of another cutaneous melanoma susceptibility gene, CDKN2A.4 The genetic etiology of melanoma

represents an area of future discovery.

The hereditary nature of cutaneous melanoma was also noted in the 1970s.5 Members afflicted with

the “B-K mole syndrome,” named after two families, acquired large, irregular, and dysplastic nevi, often

in sun-protected regions of the body such as the scalp and trunk. During this time period, Lynch et al.6

independently reported a familial association of melanoma among individuals with atypical nevi, which

he termed familial atypical multiple mole melanoma syndrome, or FAMMM syndrome, with an autosomal

dominant inheritance pattern. The 10-year melanoma risk in the setting of atypical mole syndrome is

reported to be 10.7% compared with 0.62% in control patients. Greene et al.7 approximated a 56%

cumulative risk from the age of 20 to 59 years, with 100% of patients with atypical mole syndrome

developing melanoma by the age of 76 years. An atypical nevus is not a premelanoma but represents a

genetic marker for increased risk of development of melanoma, which may occur anywhere on the skin

surface including sun-protected sites. In fact, more than 50% to 75% of melanomas develop on clinically

normal skin de novo, not in pre-existing melanocytic lesions.

Xeroderma pigmentosa is a rare autosomal recessive disorder associated with a reduced or absent

ability to repair DNA damaged by UV light. Consequently, this disorder results in the development of

multiple primary cutaneous malignancies, including melanoma as well as BCC and SCC. Individuals are

usually diagnosed with their first cancer before the age of 10 years. Unfortunately, the development of

skin cancers is relentless.

Congenital melanocytic nevi (CMN) are present at birth or appear within the first 6 months of

infancy.8 An estimated 1% to 6% of children are born with CMN. The nevi are classified by size. Small

CMN measure less than 1.5 cm in diameter and account for the majority of lesions. Medium CMN

measure between 1.5 and 19.9 cm in diameter. Large CMN, also termed giant congenital nevi, measure

20 cm or greater. This large size can lead to significant cosmetic and psychosocial implications. The risk

of melanoma development in small- and medium-sized CMN is similar to any other area of skin.

Melanoma development in small and medium CMN usually occurs after childhood and arises from the

dermoepidermal junction, making early detection feasible. Routine prophylactic removal of small and

medium CMN is rarely indicated in the absence of signs or symptoms for malignant progression.

Conversely, giant congenital nevi carry an increased risk for melanoma, with an estimated rate of 5% to

20%. Of giant congenital nevi that progress to melanoma, 70% are diagnosed prior to the age of 10

years. Melanoma can originate deep in the epidermis in giant congenital nevi. Consequently, diagnosis

within the setting of giant congenital nevi is challenging and may develop deep in the skin with a more

advanced primary lesion.

Patients with a giant congenital nevus, especially on the posterior axis, or in conjunction with many

satellite lesions are also at risk for neurocutaneous melanocytosis (NCM).9,10 NCM is characterized by

the presence of benign or malignant leptomeningeal tumors. Most patients present in the first 2 years of

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