Non-obstetric surgery during pregnancy

is Professor of Surgery and Chairman of the Department of Surgery at the University of Kentucky College of Medicine and Surgeon-in-Chief of tile University Hospital. He received his M.D. from Cornell University Medical College and trained under Doctor Wangensteen at Minnesota, where he received a Ph.D. in Surgery.- He has a keen interest in the clinical management of gastrointestinal, e n d o c r i n e and vascular disease and in teaching residents and interns proper surgical treatment of these lesions during pregnancy.

is an Assistant Professor of Obstetrics and Gynecology at the University of Kentucky College of Medicine and Attending Chief of the Obstetrics Service of the University Hospital. He received his M.D. and M.S. in Gynecologic Pathology at Northwestern University Medical School. He completed the joint residency program in Obstetrics and Gynecology at Chicago Wesley Memorial Hospital, The Chicago Maternity Center and Northwestern University Medical School and was a USPHS Trainee in Reproductive Physiology at UCLA Medical Center, Department of Obstetrics and Gynecology. His clinical and research interests are i n f e t o - m a t e r n a l physiology.

is Professor of Obstetrics and Gynecology at the University of Kentucky College o f Medicine. He is a graduate cf Northwestern University Medical School. He received his obstetric and gynecologic training at Chicago Wesley Memorial Hospital and his training in Oncology at Memorial Hospital for Cancer and Allied Diseases in New York. H i s special interests a r e gynecologic oncology and pathology.

"THE P R E G N A N T P A T I E N T can have any disease that any other woman can have except sterility.." This remark, attributed to Dr. Frederick C. Irving, brings the ~Ug]ect of this monograph iinto focus. Unfortunf~tely, the aura of pregnancy has often prompted surgical errors. The most common mistake is procrastination to assure an "ironclad" diagnosis. The basis for this delay has many origins: ( 1 ) differentiaI diagnosis is complicated by the presence of the gravid uterus; (2) radiologic evaluation would ordinarily be used; (3) con3

tern about anesthetic problems; and (4) fear of fetal loss postoperatively. An attempt is made in this report to analyze all factors involved in non-obstetric surgery during pregnancy, The first portion addresses itself tO the over-all incidence of fetal wastage and surgical complications during pregnancy, the judicious use of x-ray evaluation of the pregnant female and the tremendous adwmces made in the anesth&ic management of the operative episode. In the second part, specilic surgical entities are reviewed u n d e r the gener~d headings of abdominal conditions, vascular problems, eni:tocrine disorders, cancer and cardiothoracic disease. Evidence of the safety of modern radiology, anesthesiology and surgery during pregnancy wdl be documented, This safety is s~flicient to warrant the aphorism' When the history, physical findings and laboratory data suggest tt~e need for a surgical procedure, ignore the pregnancy.

INCIDENCES Indirect and incomplete observations indicate that about 15% of all gestations terminate prior to the 20th week of pregnancy. Of course, these figures are weighted by the reliability of abortion reporting, and-this has been shown to be notoriously poor. Baumgartner et al., in a study made in New York City, found that only one-third of pregnancies aborting in tile first tsimester , and two-thirds of those terminating in the second trimester, are reported (12). Thus, the 15 % rate is probably low. There is an additional perinatal death rate of 28 per~ 1,000 live births. Thus, at least one,fourth of all pregnancies terminate in the loss of the fetus. This figure should serve as a background against which toweigh fetal loss following an operative procedure on a pregnant female. Another aspect of t h e problem of operating during pregnancy is maternal mortality. The current nationwide incidence of deaths of pregnant females is 0.051% over-all. While the rates vary considerably depending on the source of the reports, the causes of maternal death may be related to imedical disease, e.g., diabetes, tuberculosis, etc., 0 . 0 1 0 % ; obstetrical complications, 0.032%; and surgical mishaps, 0.008%1. These figures, too, must enter into consideration of risks when discussing~a surgical problem with a pregnant patient and her husband. In f0ur studies (33, 39, 136, 173), reporting on 116,990 pregnancies, 271 inst~rnces of: surgical intervention wererecorded f o r an incidence of 0.23%1 With this low rate of surgical conditions complicating pregnancy, no physician will h a v e a large experience in the 4

management of these patients. This ,let may partially explain the reticence of a normally aggressive surgeon to wield the knife. However, the incidence ~of surgical disease complicating pregnancy will surely increase:': As wiJl be pointed out later, some surgical conditions are being seen more frequently in the pregnant as well as in the 'nonpregnant female, e.g:, bowel obstruction. Other lesions have become amendable to surgical correction and may require operative intervention during pregnancy.

ANESTHESIA Anesth"esiology has progressed far from the days of open drop ether "byguess and.by gosh." The safety of ~) patient's operation is greatly dependent on the skillful conduct of the induction and maintenance of the anesthesia. True patient safely during anesthesia is based on well~.established physiologic and pharmacologic facts. A guiding principle for surgeons must be to present the patient for emergency operation to the anesthesiologist in as sound condition as is possilale. Surgical conditions requiring immediate intervention are rare. Usually, time is sufficient to permit adequate restoration of blood volume, correction of electrolyte imbalances, preoperative antibiotic coverage, digitalization or other therapeutic manipulations. The pregnant patient facing emergency operation often epitomizes the totally unprepared individual. She is apprehensive about h0rself and her infant. Premedieation may be exceedingly dangerous or contraindicated (98). Prolonged gastric emptying may produce a full stomach despite a considerable fasting period. The older concept of the "acidosis of pregnancy" (78) has been replaced by the more correct notion of hormonednduced hyperventilation resulting in a decrease of bol~h total acid and lotal base (169). As a humoral mechanism, it is not surprising that these changes are seen quite early in pregnancy ( 1 5 5 ) . They must be remembered when using inhalation anesthesia on a pregnant patient. The supin%.hypotensive syndrome of late pregnancy consists of tachycardia, acute hypotension, pallor and sweating (96). It is seen when the pregnant patient is lyingsupine. The gravid uterus obstructs the inferior vena cava, causing incre~i~ed femoral:venous pressure and pooling, decreased blood return t ~ ~m:: h e a r t and lowered: card,ae output (Fig. I)..While seen infreqderitly in the awake individual, it can b e a significant factor during anesthesia and surgical (manipulation. The s i m p l e maneuver of changing position from supine to slightly on the left side will increase the cardiac output 1 3 . 5 % (172). The two most deleterious event~;, for the fetus (and the mother for that matter) are hypotensi0n a n d hypoxia, e v e n though the fetus 5

A _

_d_

1

FIG, l . - - W h e n the pregnant patient is in the supine position, the inferior vena cava is partially occluded between the gravid uterus anteriorly and the vertebra posteriorly.

normally exists in a decreased oxygen atmosphere (18, 19, 44, 178). The combination of the two produces an added increase in risk. Whereas :the fetus may withstand the shock of hemorrhage from peptic ulcer bleeding or following trauma in the mother, hypoxia accompanying the hypotension, such as may occur during induction or later in anesthesia, quickly leads to fetal embarrassment~ or death. Since temporary maintenance of sufficient volume can be readily obtained with adequate amounts of electrolyte solutions (190), no patient should be anesthetized without at least partial restoration of vascular volume. Appropriate arrangements for colloid replacement should be initiated when :hypotension is recomaized preoperatively; it follows that during the::period of anesthesia a fall in blood pressure must be avoided q~y having suitable replacement fluids available. The choice of anesthetic agent is crucial as far as providing sufficient pO2 to mother and infant. Spinal anesthesia for surgical conditions below the umbilicus would seem to permit adequate blood oxygenation ~ throughout the anesthesia-operation episode. The fig~ures comparing spinal and inhalation anesthesia do not bear out the theoretical superiority of the former technic. Moreover, many of the lesions :requiring a n operation=during pregnancy cannot be managed by spinal anesthesia. The i d e a l :inhalation agent in this circumstance should provide rapid reduction, ~ . . concentratmns . high of O.,_ in the gas mixture, minirnal~effect on the fetus and insignificant postoperative effects. The anesthesia: literature reports the data on many of these points, and they m a y b e s u m m a r i z e d as follows: (1) because of the known cardiopulmonary changes associated with pregnancy, the uptake of inhalation agents is greatly.:accelerated. ( t 5 2 ) . Thisallows rapid induction but also enhances the potential danger of overdosage; (2) most of the volatile agents can b e combined w i t h concentrations o f oxygen that N v e a ~eat:margin of lsafety. On the other hand, nitrousoxide and chloroform may n o t permit l such safety; (3.) placental transfer of drugs.:has always been of major .interest to many investigators. Most substances:~ cross the :placenta by diffusion as. though a lipid barrier 6

existed. Consequently, the rate of exchange is governed primarily by the fat solubility of the non-ionized molecule (15.1). The molecular weight also is: important; in general, the lower the weight the. more rapid the entry.. Volatile anesthetic agents, possessing high fat solubility and low: molecular weight, show fast placental transfer.' They also disappear rapidly from th.e fetal circulation. As a contrast, most muscle relaxants, because of high molecular weight and low fat solubility, do not cross the placenta easily (113). As far as the fetus .is concerned, this may be a fortunate circumstance. LOw concentratimls of a volatile agent will produce a light anesthesia while mmximal muscle relaxation in the mother may be obtained without providing a harmfuI drug environment for the fetus; and (4) most of the newer agents do not have the unpleasant postoperative effects so notorious after ether anesthesia. Halothane'deserves special mention (152). It provides rapid induction and maintains anesthesia at~concentrations, less t h a n 2%. Although it was originally thought to have little effect on i:he fetus, Montgomery (149) showed that halothane produced more fetal depression than a combination of thiopental, nitrous oxide and succinylcholine when used during delivery. The depression was riot marked and probably related to decreased uterine blood flow. Halothane is rapidly, equilibrated across the placenta during both induction and recovery, and has little adverse postoperative effect. An additional benefit of halothane when-operating on a pr%maant woman not near term is its well-documented uterine relaxant ability (53, 148). From the anesthesia literature the distinct impression is gained that the modern-day improved outcome of anesthesia in non-obstetric operations in pregnancy was better correlated with the experience, ability and knowledge of the reporting anesthesiologist than with the technics described. A s more basic information is c o l ! e c t e d a n d d i s seminated, and t h e expertise of the anesthetist is increased, better maternal ~and fetal survival rates can be expected even in desperate situations.

RADIOLOGY Whether the amount of radiation: °xdelivered to the fetus during diagnostic studies of the mother conSUmtes a significant danger is not certain. The report in 1958 by S~ev~'art et a l . . ( 1 9 7 ) , indicating an increased iffcidence of leukemia and cancer up to 10 years of age in chiidren-Wh0se .mothers received abdominal irradiation during pregnancy, has undoubtedly inhibited the use of diagnostic x-rays in pregnant women. This report has been both substantiated (:126)and opposed (196, 215). In fact; Sterling and his co-workers ( I 9 6 ) have 7

pointed out that if other variables such as older mothers, number of primiparas and instances of toxemias,, threatened abortions and past histories of abortions had been carefully screened, the difference in cancer rate between controls and the group de.veloping childhood tumors in Stewart's series would have been insignificant. Stewart herself (197) has now expressed doubt that many cases of leu'kemia are the result of this type of irradiation. The problem of possible gene mutations secondary to gonadal irradiation still exists (147). While recognizing these potential dangers and acknowledging the fact that some diagnostic studies may be safely delayed until after delivery, nevertheless undue concern about fetal harm should not deter one from using a technic that may be essential to the solution of the immediate problem. The radiologist may be a b l e to suggest means of obtaining the most meaningful infermation with the least amount of fetal exposure. Diagnostic radiology during pregnancy is Fro. 2 . - - T h e 20-minute film of an intravenous pyelogram in a pregnant patient. Note th

8

not necessarily an occasional event. In one study, 565 radiographic examinations were carried out on 2,072 pregnant women (163). These included 126 examinations of head, extremities and spine and 21 studies of the gastrointestinal tract and abdomen. For example, if an upper gastrointestinal tract s t u d y is required, the use of a well-collimated x-ray beam and adequate fetal shielding are essential. The radiologist, forewarned, can limit the amount of fluoroscopy and the number of films used much as he would lessen the palpation in doing a GI series for a bleeding ulcer. Likewise, an intravenous pyelogram, usually done for obstructive symptoms in a pregnant woman, can be redficed to a single film at 15 or 20 minutes (Fig. 2). The cardiologist also should limit the fluoroscopy time during catheterization and may eliminate serial x-rays if the pressure and gas data will suffice for proper diagnosis in an emergency.

GENERAL ABDOMINAL CONDITIONS An acute abdominal crisis occurring in pregnancy is always perplexing. First, one must decide whether the symptoms and sigris are related to the pregnancy, e.g., broad ligament stretch or hemorrhage, abruptio placenta with concealed bleeding or urinary tract obstruction and infection. Second, the history may include heartburn, epigastric distress, constipation and various types of abdominal distress which often accompany pregnancy. Third, the Classic clinical signs are often obscured by the enlarged uterus itself or displaced to abnormal locations~ The stretched abdominal muscles do not respond in the usual fashion to peritonealinfection, and palpation of masses is difficult. Here, then, the judicial use of adjunctive diagnostic tests may be crucial. An appropriate intravenous pyelogram may rule out a ureteral stone, recognizing the usual ureteropelvic dilatation seen in the last two trimesters of pregnancy. An abdominal tap may be done in cases of suspected peritoneal sepsis as long as negative findings do not persuade one to unwarranted procrastination. Delay can only be condemned. The effects on the fetus of a properly conducted anesthetic and operative procedure on extragenital abdominal organs are small, though not to be taken lightly. The same statement can be made regarding ;the mother; awaiting obvious sepsis, vascular impairment or othe'~ &atastrophe is disastrous. Douglas (46) put it in proper perspective when he wrote in 1950: "If a policy of earlier and more frequent operation is adopted for what may seem at the time relatively benign symptoms and signs, it may be anticipated that a certain number of.patients will be operated upon needlessly. In view of the insignificant risk involved it is apparent that this'is a small price to pay compared to the tragedy following procrastination . . . " 9

AI, PENDIClTIS.--The correct diagnosis of this entity at any time carries a justifiable 20% error. The presence of a gravid uterus compounds this. Early, as the uterus ascends out of the pelvis and turns slightly, strain on the right round ligament produces lower quadrant pain on that .side. This must be differentiated from the pain of appendmitns. Later, uterine enlargement displaces the appendix upward and to the right (Fig. 3), causing the pain of appendicitis to be appreciatedl progressively higher. A usual leukocytosis during pregnancy makes this guide unreliable. Urinarytract symptoms and abnormal findingsare common in pregnancy and rare in appendicitis during the non-pregnant state. The development of appendicitis during pregnancy, while no more likely than in the absence of pregnancy, is often more fulminant. The increased pelvic vascularity and some displacement of the appendix b y the uterus may hasten the strangulation; increased local lymphatic drainage, interference with omental migration and the higher circulating adrenocorticoids favor Systemic spread of the inflammatory process. No wonder Warfield states that "the-mortality of appendicitis (during pregnancy) is the mortality of delay" (213). Fla. 3.wDisplacement of the appendix upward and to the right as pregnancy progresses. (From Baer, Reis and Arens [9] by permission of the attthors.)

8mo.

,Tmo.

~)

~Oortt~ ")

"" "

J:

/ 10

e'

./

)

i

i 1 _ _ _

i

i

u

.

i

_

|

_

-.

ii

_

ii

TABLE I,~AcU'rE ApPENmcrrm DURING PREGNANCY A UTHOR

NO. CASES

First

TRIMESTER Second

Third

Varner (207) Meiling (1.42) Hoffmnn & Suzuki (90) Black (17)

56 26

16 9

21 11

19 6

45 358

18 130

15 127

12 101

174 (35.9%)

138 (29.4%)

485

TOT^L .

.

.

.

.

.

.

.

:

J

ii

173 (35.7%) . . . . .

~1

I

I

II

I

I I

McDonald (137) reported in 1929 on 274 cases.of appendicitis accompanying pregnancy. These were the collective experience of members of the Western Surgical Association and surgeons in the Scandinavian "countries. When the di.sease was limited to the appendix, the fetal death rate was 11.4%, contrasted to a 72% fetal loss when generalized peritonitis occurred. Twenty-five years later, HoflYnmn and Suzuki (90) found that the fetal death rate was still 11% when only the appendix was involved, but the fetal loss had risen to 35% in the face of peritonitis. Acute appendicitis may occur any time in pregnancy, although it is seen a little more frequently in the first two trimesters (Table I). A history of previous episodes of right lower pain prior to the pregnancy is valuable information; correlation of this with acute appendicitis during pregnancy is high. Abdominal tenderness should be elicited, at.though it may be displaced. Alders (5) has described a useful technic of differentiating tenderness of extrauterine cause from uterine or tubal origin. After locating the point of maximal tenderness, pressure is maintained while the patient turns onto he:" left side. Persistence of tenderness is most likely due to an extrauterine lesion; relief from the pain signifies a genital tract disorder. The usual leukocytosis of pregnancy will cause the white blood cell count to b e higher than would be seen with uncomplicated acute appendicitis; abnormal urine sediment and bacteria may only confuse the issue. Thus, serial abdominal examinations i n t h e absence of analgesics are the mainstay of diagnosis.

Solution of ,this clinical dilemma has almost reached the stage of paraphrasing the old adage about t~acheostomies: :"If you :think it's appendicitis, operate on the patien$.'\ Recent results justify this concept. The mmdence of normal appehd{lc~s removed during pregnancy has been reported to be as high as 41.6% (25). Concomitant with this have been reported fetal losses of only 0 - 4 % following appendectomies when the appendix was normal or the only involved structure, and only 8 - 1 0 % loss when peritonitis ensues (17). I n t h e latest reported series, 'there has been no maternal mortality (121, 204). 11

The conduct of the operation is straightforward. It is empllasized here, but holds true for all abdominal lesions requiring operation during p r e g n a n c y : gentleness is paramount, a n d u t e r i n e handling and retraction should b e minimal. Spread o f infection must be avoided, and antibiotics probably should be used in all cases. The use of postoperative progesterone to decrease the incidence of abortion was reported first by Lackner and Tulsky ( 1 1 4 ) . In 1939, their abortion rate was ionly 5 % when progesterone was u s e d . Since then; posto p e r a t i v e progesterone prophylaxis has had its advocates and its detractors. Thirty years later, progesterone therapy after appendectomy was reported as the possible reason for a lower abortion rate ( 2 0 4 ) . N o controlled studies have been conducted, but most recent reports d o n o t include progesterone t h e r a p y in t h e postoperative management.

CASE REPORTS

1) L. C. ( U K M C # 0 2 - 1 8 - 6 4 4), a 19-year-old white, married, gravida 2, para 1 with LMP 23 November 1963 was admitted 10 March 1964 with acute onset of right lower quadrant cramping abdominal pain 6 hours earlier. The pain~'was associated with some increase in nausea and vomiting which she had been experiencing for several weeks. She had a normal bowel movement justprior to admission. Urinary complaints were absent and she had had no vaginal bleeding. There was marked tenderness in the right lower quadrant of the abdomen with rebound tenderness and referred pain to that area. There was moderate guarding over McBurney's point. Bowel squnds were absent. Pelvic examination confirmed the intrauterine pregnancy. Her admission laboratory work was normal except for a WBC of 13,500 with shift to the left. The admission diagnoses were acute appendicitis and 12-week iritrauterine pregnancy. Through a McBurney incision an acutely inflamed appendix was removed. The abdomen was not explored further other than to confirm the enlargement of the uterus and irrigateadequately the right lower quadrant. The incision was closed primarily and the patient had an uneventful postope?ative course. She was readmitted 6 September 1964 in active labor following an uneventful prenatal course and delivered an Apgar 9, 3,200-Gm. female infant without difficulty. Mother and infant left the hospital in good condition. 2) L. E. ( U K M C # 0 0 - 7 9 - 0 6 I), a 19-year-oid gravida 1, para 0, was admitted 16November 1968. Her EDC was January 1969, but she complained of abdominal p a i n ? o f 3 days' duration. Thelpain b e g a n in both lower quadrants of the abdomen a n d w a s associated with obstipation and frequency without idysuria. In 1966, she had undergone bilateral ureterocystostomy and YV, plasty f o r chronic ureteral reflux. Physical examination showed a temperature of 101 ° rectally, a diffusely 12

tender abdomen, more,.so in the right lower quadrant, and rebound tenderness. The uterus was 4 cm. above the umbilicus; bilateral C V A tenderness was present;! bowel sounds were hypoactive and high.pitched; the fetal heart sounds were present; cervix was closed; and there was tenderhess on the right rectal examination. The hematocrit was 3 8 % , t h e white cell count was 7,600 witli a shift to the left, and the u,rinalysis-showed many leukocytes and bacteria. ' Abdominal films demonstrated a .few air-fluid levels and obliteration of the lateral peritoheal line on the right (Fig. 4). A diagnosis o f possible acute appendicitis was made despite the abnormal urine findings. She was explored through a right paranaedian incision on the evening of admission; a perforated appendix was found ~.md removed. The uterus was manipulated minimally. T h e abdomen was drained after thorough irrigation with saline. She was on intravenous Kellin before, during and after operation. The E. coil recovered from the peritoneal cavity was sensitive to erythromycin, and this was added to the regimen since she remained febrile for 3 days postoperatively. Her course thereafter ~was benign, and she was discharged on 24 November I968. On 18 January 1969 she delivered an Apgar 9, 3,115-Gin. female infant without complications. Mother and infant left the hospital in good' condition. Fro. 4.--Upright abdominal film in a pregnant patient complaining of generalized pain,/ but has been obliterated

13

BILIARY. TRACT DISEASE. Acute cholecystitis is a rare condition in pregnancy. Hamlin et al. (73) found only 4 instances in 26,341 pregnancies foUowed at the Boston Lying-in Hospital. Sparkman reviewed 176,614 pregnancies in a 1957 report (193) and described 11 cholecystectomies during pregnancy; 6 for acute cholecystitis. The greatest difficulty is distinguishing acute gallbladder disease from appendicitis, since ;the appendix often lies close to the gallbladder, especially in thethird trimester. Past history may provide a clue. Often.the pain radiates to the back with cholecystitis. Non-operative therapy o/~ acute cholecystitis during pregnancy is recommended, but if the diagnosis is inany doubt, exploration should be done. Pregnancy undoubtedly predisposes the female to the development of cholelithiasis. A't least three factors are responsible for this: (1) bile stasis; (2) increased concentration of cholesterol in gallbladder bile; and (3) changes in the physicochemical nature of bile salts. However, complications of gallstones occur infrequently dm'ing pregnancy. As already depicted, cholecystectomy during pregnancy is uncommon, and the removed gallbladders contained stones in less than 50%. Jaundice occurring during pregnancy presents a more difficult diagnostic problem. In a. comprehensive review of this subject, Haemmerli (7I) (also published as Supplement 444, Acta reed. scandina7.) tabulated 456 instances o f jaundice during pregnancy. Hepatitis ( 4 1 , 5 % ) a n e l cholestasis (20.6%) accounted for the majority Of cases. Twenty.seven patients (6.7) had common duct stones. PreVious: symptoms suggesting cholelithiasis should alert the physician to the possibility of common duct calculi. Changes" in serum enzymes are of paramount importance in making an accurate diagnosis. The transaminase values ordinarily do not change in pregnancy, s o a rise in the serum transaminases in a jaundiced expectant woman signifies hepatocellular damage and the probable diagnosis of hepatitis or cholestasis. The latter entity presents a particular problem ir~ wegnancy. It occurs without apparent etiology during gestation; but may accompany ingestion of certain drugs. A careful drughistory must be obtained during pregnancy, as at any time. Alkaline~phosphatase elevation does not necessarily indicate comm o n d u c t . obst~ction,; since it.occurs in pregnancy particularly after the seventh imonth(194) i. Needle biopsy of: the liver m a y clarify the situation (71)i~ since o p e r a t i o n is likely to increase the liver damage of hepatitis, a!! diagnostic avenues: should be used. However, if acornmort duct/st6ne c~nnot: be: ruled out, operation must be undertaken early t0:av0idl theldevelopment o f permanent! liver injury, Choledochotomy wit~::/removal,of: the;stone and T'tube drainage i s the procedur e of choice and~can be performedi with safety to mother and fetus ( 2 0 9 ) . 1,4

Gastric acid output decreases during pregnancy (143, 201). Clarke (34) found that during 313 pregnancies in 118 women who gave.a history of previous duodenal ulcer, 88% experienced a remission. Nevertheless, heartburn occurs frequently during pregnancy, and epigastric distress is common. These symptoms make a definitive diagnosis of acute peptic ulcer, during pregnancy difficult. Obviously, uncomplicated ulcer disease should be treated medically. The complications of perforation and hemorrhage, though rare in pregnancy, are no less dramatic than in the non-pregnant and even more urgent. Perforation of an ulcer occurs almost exclusively in the third trimester ( I 8 5 ) . In late pregnancy, the gravid uterus and somewhat relaxed abdominal musculature may interfere with the development of the rigidity expected with a perforated viscus. X-ray films showing air under the diaphragm, particularly in the lateral view, should lead. to a correct diagnosis. Horwich reported a single case deliberately treated with aspiration (95). A stillbirth occurred 40 hours later, and the patient required laparotomy thereafter. A number of successful cases of operative closure have been reported (43, 105 ), and this remains the treatment of choice. A bleeding duodenal ulcer in pregnancy is rarer than a perforating one, but it is more serious because of the threat of ralbid development of shock. The third trimester is the most common time of the hemorrhage, although toxemia may lead to this complication of an acute ulceration (116). Pregnancy and bleeding peptic ulcer represented a deadly combination fer mother and fetus until the past two decades. In fact, in 1947, Le Winn (119) described a case of ulcer bleeding to a hemoglobin of 2.7 G m . / 1 0 0 ml., and he considered surgery "out of the question." A more aggressive attitude is now prevalent. The treatment of a bleeding ulcer in a pregnant patient is exactly the same as in a non-pregnant one: resuscitation, blood transfusion and surgical intervention if bleeding does not cease. The last few reported cases of bleeding ulcer operated on during pregnancy bear this out. There were no maternal deaths and several fetal survivals ( I 0 9 ) . Although as late as 1969 Jones et al. ( 1 0 5 ) recommended cesarean section followed by surgical attack o n : t h e bleeding ulcer if the hemorrhage occurs quit~..late in pregnancy, it seems more sensible to man~i~ge the ulcer first. Hemorrhage is stilithe life-threatening event a n d if section can be avoided, it ~is probably better. INTESXINAL OBSTRUCTION. ~ ¢ i d i a g n ° s i s of intestinal obstruction should not be d~fficult. However~ w~mmng assocmted with obstruction, occur.ring early in pregnancy, m a y be disregarded; the pain of bowel obstruction coming on late. in pregnancy may be mistaken: for the welcome onset of labor. Since adhesions are the most common cause of obstruction in pregnancy (as well as at a n y other time);:an PEPTIC

,

ULCER

-

DISEASE.

L.....

~i~

15

,

~,

.

.

.

i

.

abdominal scar should warn the physician. A thorough eliciting of tile colicky nature of the abdominal pain, the finding of peristaltic rushes, and air-fluid levels on upright abdominal x-ray films will confirm the diagnosis of bowel obstruction. The surgical management of intestinal obstruction during pregnancy is exactly the same as in the absence of pregnancy. Early intervention to avoid strangulating obstruction leads to the most satisfactory results. Of I0 cases reported by Harer (74), 9 were operated on, 5 had closed-loop obstruction, 3 required resections and there were 4 fetal deaths. No mothers succumbed. This author makes the valid point that intestinal obstruction occurring during pregnancy will undoubtedly increase as the nunibdr: of abdominal operations on females prior to child-bearhlg rises. The patient who was not operated on by Harer (74) had obstruction of the sigmoid colon by the gravi d uterus. This same syndrome has been reported as a postpartum event (30). If recognized by the generalized air-filled loops of intestine on x-ray examination, the lack of systemic symptoms and perhaps the absence of a surgical s~car,"it can be treated effectively by having the patient assume the knee-chest position. PAYCREATITIs.~Acute pancreatitis may develop any time during pregnancy. It is rare and may not be associated with either gallbladder disease o r alcoholism. As with jaundice during pregnancy, a careful drug history must be elicited. Chlorothiazides have been implicated as an etiologic:factor in pancreatitis. The greatest difficulty of pancreatitis ~ distinguishing it from a condition requiring surgical intervention. If the diagnosis is firm, treatment should be non-operative. Whenever doubt exists, exploration should be performed. If pancreatitis is found, the pancreatic bed must be drained adequately. In a review of 53 cases o f pancreatitis during pregnancy,,Langmade and Edmondson ( 1 1 7 ) r e c o r d e d 38 instances of operation. There were 6 deaths, all postoperatively, HERNIAS. Any hernia of the abdominal wall represents a potential threat. As gestation progresses, increasing intra-abdominal pressure worsens the hernia. In several series totaling more than 200,000 pregnancies (192) only 6 patients with hernia required operation for incarceration. Moreover, not all inguinal swellings are hernias. Hodgkinson and Kroll (89) reportedon 8 patients followed through 21 pregnancies during which inguinal swellings were detected in all. Only 2 h a d a definite hernia. Here is an instance where preventive measures are significant. Any girl or young woman, particularly one undergoing a premarital exam, ination, who has a hernia should be advised to have it corrected. A definite hernia found early in pregnancy can be repaired without undue r i s k and it should be. The pregnant woman ~,ho does not 16

wish the hernia repaired should be warned of the symptoms of incarceration.. Strangulation in a hernia must be avoided at all costs. Any hernia detected and not repaired should be operated on sometime after the delivery. TRAUMA.,-- Accidental death has risen rapidly to tile number 3 position in national mortality statistics. Many more indivicruals are injured, and pregnant females will necessarily be involved in accidents more frequently each year. A comprehensive review of the problem of accidental injury and pregnancy has been published recently by Buchsbaum (27), and the present monograph cannot improve on his lucid presentation or reference material on the subject. Some points made in that article are worth reiterating. The accident rate during pregnancy had reached 6 . 9 % by 1963. Even more distressing, trauma accounts for about 15% of the nonobstetric maternal mortality and is increasing steadily. When considering fetal deaths, several aspects assume importance. Although the concept that injury of the mother leads directly to abortion began in ancient cultures and still is upheld in present-day litigations, the fact is that traumatic abortion is extremely rare; often, an examination of the material aborted after trauma will show defective ova, fetus or placenta. In early pregnancy, the uterus is protected by the bony pelvis, and the fetus by the relatively greater amount of amniotic fluid, which absorbs the force of the trauma. Even in late pregnancy, ~ ' this shockabsorptive ,capacity of the uterus will provide significant protection (see the following Case Report). Blunt or penetrating abdominal trauma can cause direct injury to the uterus and fetus, but, more important, it may result in aberrations of maternal homeostasis which can jeopardize the fetus ( 18, 19, 44, 179). Remote trauma need not influence the p re~,nanc ., y, but the management of the injury may be modified by the presence of the gravid uterus. Extremity fractures are treated in the fashion promising the shortest enforced bed rest. Protracted recumbency in a pregnant woman will add to the already higher risk of thromboembolic disease and will cause increased calcium excretion which is detrimental to fracture healing as well as to the developing fetus. Thus, internal fixation is preferred over prolonged traction. Chest trauma is mentioned only to emphasize the need to prevent hypoxia. The airway is crucial, and rapid intubation or tracheostomy should be performed whenever necessary to maintain maternal an&fetal oxygenation. Pneumothorax ~,~ .~, . ' .... and flail chest must be treated exl316d~i~tlously. The axiom of ignoring the pregnancy and treating the immediate problem in the mother is paramount in the management of traumatic injuries. These are, in the order of priorities: (1) proper blood oxygenation, wliich dictates a clear airway, and adequate gas exchange, 17

which may requirepositive pressure breathing; (2) stable blood pressure, which follows control of external bleeding, and intravenous administration of balanced electrolyte solutions followed by blood replacement when available; (3) thorough diagnostic ev~duation, which: must be. prompt when the hemorrhage is internal ~md lifethreatening; and, (4) proper treatment based on the lindings. CASE REPORT

E. O. (UKMC # 11-79-1.9 I.), a 21-year-old white,-married, gravida 1 with EDC 28 April 1969, was admitted on 3 March 1969,3 hours followFxG. 5..-Left retrograde pyelogram in a pregnant patient after an autonlobile accident. Intravenous pyelogram had been done 10 minutes earlier. Note the marked, persistent dilat~ltion on the right side. The left kidney,, which did not visualize on 1VP, has been ~disrupted. Arrows point to frzuz~:es of the left eleventh rib ~md left p u b i c bone.

18

ing an automobile accidenl, complaining o f l e f t llank and left upper q.uadrant ahdomitml pain. She votnited, l~lood-slained material and. gave a history of previous episodes of bloody emesis, "l'he blood pressure was 60/20 o n admission bul responded prumptly Io intravenous laclated R,inger's solulion.~ Physical Iindings were negative except fur pai., tenderness and .tel:rot.llid tenderness in lhe t~pper abdomen and left, .ll~mk. "l"he ul.ertts was Sol'~ and of 33 weeks' size. l,'etal heart tones were heard at 1401min. She llad grossly bloody 'urine, ,~o an IVP wus performed. Fractures of a rib and of. t!le pelvis were seen. "l'lle righl kidney al]d ureter were normal for this stage of l~regnancy. 'lhe left kidney did nol visualize and a retrograde pyelol,,ram showed a ruptured left kidney (Fig. 5 ! . S h e wad taken to the operaling room 43 Jnillutcs alter admission, :with :the preoperative diagnosis of fractured left .kidney alld possible rupttzred spleen. Her abdonmn was opened througt~ a SUlm,uml:~ilical midlinc incision which was extended lat;:"'-~lly to the left Ilatlk. The rt!j;~tttred N)teen and fractured left kidney weft removed. I?ottr ulli!.*i of blood were replaced. She had an tmevenlful posloperalive course except for transient etcV;,tliO~l of imr BUN to 2]5 mg,/100 ml. l)'etak he;trt tones r.emained a t approxio mately 140/rain. throughout her course. On I4 March 1969 she wus admitted in labor with mild preecla~np~ia (liP 150/90 with 3 + rellexes, urine negalivc for protein), She delivered vaginally without dilticuity an Apgar 10,.2,095-(.,jm. nmle by eleclive low tTorceps under low ,spinal anesthesia, Mother and baby left the hospital o~ 18 March 1969 in good condition.

/ASCULAR PROBLEMS Significant arteri~l ai~d venous disdase may b e encountered in pregnancy. Arteriosclerosis is rare, althougt5 not unknown, and peculiar changes in the splenic artery and spleen ~trc seen during pregnancy. Most of the venous problems occur boca.use of obstruction by the uterus and arc generally a third-trimester problem. Obvious h e r e o f rhagc or unrelenting vascular" block must be treated ~urgicaliy. HF.MOitRr.~OH)S.---Onc of the most common complaints during pregnancy is hemorrhoids. Pressure froth tt~e gravid,utcrus,-proge~o terone-induced change.:in collagen in'the walls of the vein~rand constipation all predispose to their development. Usually, they can be treated symptomatically with local ane:sthetics, witch hazel and stool softeners. Patients should be instr~!cted in digitM replacement of prolapsed or pt'otruding veins..When, t~,~rombosis of a vein occurs, it usu~, ,~., aria ); , packs. If this is unsuccessful, ally can be tr eatedwith hot soaks evacua~iorr of the thrombus may be done under topical anesthesia in the office, Operative removal of tiemorrhoids is rarely necessary dor-. ing pregnancy, but can be successfully undertaken..Following.pregnancy, most hemorrhoids.wilt regress to a n a s y m p t o m a t i c state. 19

VARICOSE VEINS. --They frequently first appear during pregnancy,

usually become worse as the uterus enlarges, regress but do not disappear following parturmon, and occur in 10-20% of pregnant women (55, 153, 154, 171). Recent studies show that pregnancy has profound effects on collagen throughout tim body, but especially in vessel walls (42, 131). There are conflicting reports concerning whether venous tone is decreased during pregnancy (48, 64, 135). Most investigators believe that pregnancy changes the venous wall sufficiently to allow decreased tone and a tendency for w~ricosities to develop. However, genetic predisposition or other factors must also be present, since not all women have varicose veinsduring pregnancy. The incidence of phlebitis and thromboenibolism in pregnant patients with varicose veins is low--phlebitis 5% and embolism 0.7%. However, the incidence of other symptoms is extremely high, and they become progressively worse as pregnancy approaches term. Ankle and calf edema, pain, tenderness, skin discoloration and dermatitis'over the varices are common complaints. Hemorrhage from a ruptured varix occurs occasionally. Disagreement concerning treatment of varicose veins during preg-. nancy is marked. Nabatoff (1.53) believesthat these patients should be treated symptomatically with elastic bandages, rest and elevation until regression has occurred in the puerperium. Varicosities that persist several months post partum should be ligated, along with stripping of tile saphenous system. Many will regress so that an operation is not required. Fanfera and Pa]mer (55) state that the patient "~hould be treated for symptoms during pregnancy with elastic bandages, but should have ligation and stripping on the third postpartum day. Regression floes not represent cure only postponement of symptoms until the fiext pregnancy. This approach obviates operation during pregnancy and does not prolong hospitalization beyond the sixth postpartum day. Quattlebaum and Hodgson (171 ), reporting a series of 90 patients, believe that ligation and stripping may be done during pregnancy in the middle trimester. They require existence of varicosities and insufficiency prior to the pregnancy or a history of phlebitis as indications for operation during pregnancy. They reported no complications from operations performed during pregnancy. When the patient is not seen early enough for an operation to be done by the early part of the third trimester, they believe that it should be postponed until the early puerperium. All groups agree that there must be long-term follow-up, with reoperation or injection of sclerosing agents for new varicosities or recurrences. Quattlebaum and Hodgson (171) report a recurrence rate requiring reoperation of 16.1% in 90 patients originally operated on during pregnancy,: compared to 1 4 % in 152 patients operated on originally •

I

20

when non-pregnant. Subsequent pregnancies (avg. 1.2), thrombophlebitis ( 1 J % ) and follow-up failure ( 2 2 % ) were the main reasons for recurrences. Asympt0mzttic varicosities in pregnancy that do not exist when the patient IS non-pregnant should be treated with support stockings. Varicosities ttmt are severe enough to require elastic bandages or in which thr0mbophtebitis has devlsloped should be treated by ligation and stripping either in the middle trimester of pregnancy or in the early postpartum period. There is no reason to postpone definitive operative therapy until the patient has completed her family. Reoperation is relatively easy when necessary and during the interim needless suffering is avoided. The recurrence rate is approximately the same whether or not the initial procedure is done during pregnancy. THROMBOPHLEBrrls AND Tlzli~.OMBOEMBOLISM. Thrombophlebitis of the veins of the legs or pelvis is relatively uncommon during pregnancy. Ho,;vever, its incidence increases tremendously in ~hc puerperium. Husni et al. (97) report an over-all incidence during preg, nancy of 1:1,174 (0.085%) and 1 : 3 6 7 ( 0 . 2 7 % ) postpartum. These are further subdivided into antepartum superficial thrombophlebitis 1:1,957 ( 0 . 0 5 % ) , antepartum deep I :2,936 ( 0 . 0 3 % ) , postpartum superficial 1:534 (0.18%) and postpartum deep 1:l,174 ( 0 . 0 8 5 % ) . Aaro et al. (1, 2) report an incidence of 1 : 5 4 5 ( 0 . 1 8 . % ) in pregnancy (superficial I : 6 7 8 . 0. I4%~ and deep 1 : 2 , 7 8 7 ~ 0 . 0 3 % ) and of 1"75 (1.33%) postpartum (superlicial 1:84 ...... 1.19%, and deep ] : 6 6 - - 0 . 1 5 % ). Villa Santa (208) reports an over-all incidence of 0.027% during pregnancy. The wide variations in incidene-e repot.ted above are not easil~ explained. Race, socioeconomic status and parity do not seem to be involved. Geographic location may be important (13). It is difficult to explain the difference in incidence between pregnancy and the postpartum period. Pregnancy leads to hypercoagulability of blood, and yet the incidence of thrombophlebitis is much lower then than in the puerperium, when blood coagulability has returned to normal (13). Other than pain, tenderness, fever and limitation of activity, the main com~!cation of thrombophlebitis is pulmonary embolism. Husni et aI. (97) report an incidence of 1:8 in antepartum deep thrombophlebitis, I:4 in antepartum superficial, 1:5:5 in postpartum deep and 1:44 in postpartum supe~rficial. Aaro et at. (q, 2) report 1:4.5 in antepartum deep, none ~in',..~ntepartum superficial, 1:6.3 in postpartum deep and 1:297 in:~ ffostpartum superficial thrombophlebitis. ~7,loore e t aL ( 1 5 0 ) stated that b y 1..967 the incidence of pulmonar.y embolism had decreased to less than I in~3,000. No maternal deaths occurred in the preceding 24 years from pulmonary embolism. 21

The diagnosis of antepartum or postpartum superficial and deep thrombophlebitis is best made by clinical symptoms, signs and physical findings. Distinguishing between superficial and deep venous involvement is important. Usually, the thrombosed superficial veins can be palpated, and local tenderness is present. Deep thrombophlebitis during pregnancy will present as pain in the calf, particularly with dorsiflexion of the foot, increased heat ,and tenderness over the inflamed vein, and some edema (1, 2, 97). It may be bilateral. Treatment of thrombophlebitis during pregnancy is basically nonoperative--rest and elevation, anti-inflammatory agents and an'ticoagulants. Aaro et al.. (2) recommend that antepartum superficial thrombophlebitis be treated with bed rest, heat and elevation. Occasionally, phenylbutazone is used for patients with marked inflammation. Husni et al. (97) recommended anticoagulation as the .therapy of choice for any thrombophlebitis, whereas Aaro et al. ( 2 ) reserve anticoagulants for deep thrombophlebitis. Intravenous dextran infusion has been used by several groups during pregnancy, and all report good results in small numbers of patients (97, 150, 208). Anticoagulant therapy during pregnancy is potentially dangerous to the fetus by causing either retrop!acental hemorrhage or fetal hemorrhages during labor and delivery. The antiprothrombin compounds have been shown to cross the placenta (184), and fetal deaths and damage have been attributed to these drugs. However, Aaro et aI. (2) and Jennings and Hodgkinson ~(100) :believe that oral anticoagulant therapy can be .carefully managed during pregnancy and is safe. Heparin probably does not cross the placenta (59) but must be administered parenterally. It is theoretically safer, but more cumbersome to:use. Although there has been some controversy regarding this, anticoagulation can probably be safely continued through labor and into the puerperium. Dextran therapy in pregnancy needs further investigation but appears to be safe and quite effective in the tregtment of early thrombophlebitis, whether superficial or deep. The advantage of dextran therapy is that 500 ml. of low molecular weight variety per day is the only intravenous fluid needed; no clotting studies are required. When combined with rest, elevation and symptomatic relief, this should be adequate in the treatment of superficial thrombophlebitis. If improvement is not immediate in either deep or superficial thrombophlebitis, heparin therapy should be started. The heparin is continued for 5 or 6 days after symptoms and positive findings subside. Recurrences are uncommon and c a n be treated as necessary, Venous interruption is reserved for patients with multiple emboli who do not respond to other therapy. Thrombophlebitis of extremity veins post partum requires the same treatment as during pregnancy. Ovarian vein thrombophlebitis is a 22

rare complication of pregnancy and the postpartum period (50, 106, 122, 124). Any. patient with postp'artum fever believed to be secondary t o parametritis which does not respond to appropriate antibiotic therapy must be a suspect for unrecognized pelvic.thrombophlebitis f5Q). Heparin may produce dramatic improvement. The great danger, withthis entity, a~ with an3' thrombophlebitis that is not relieved by anticoagulation, is pu~fmonary embolism. Sudden pleuritic chest pain, bloody sputum-and tachypnea in any patient should arouse the suspicion of pulmonary embolism. This is especially true in a pregnant or postpartum woman with unexplained fever or unequivocal thrombophlebitis (54, 88). Physical findings may be scarce'; a chest x-ray may be unchanged. Radioisotope lung scan is easy on the patient but may be misleading (150). An accurate diagnosis.is best made by pulmonary angiography (61). Intravenous heparin therapy must be instituted whenever there is strong evidence for pulmonary embolism. The benefit of anticoagulant therapy was clearly shown in a study by Ullery (206), who, on review of 135 instances of pulmonary embolism during pregnancy and the paerperium, found 15 deaths among 97 Jpatients not treated with anticoagulants compared to no deaths in 38 patients on adequate anticoagulation. The indications.for more aggressive treatment in this condition are the same as in the non-pregnant state. More than two episodes of embolism, continued embolism despite adequate anticoagulation, and septic emboli dictate inferior vena caval interruption. Several cases of inferior vena caval plication or ligation with or without tying .the ovarian vein during pregnancy have been reported (176, 181, 199). Neither mother nor fetus suffered ill effects. Pulmonary hypertension may occur as a late complication of pulmonary emboli (58, 160). RUPTURE OF SPLEEN OR SPLENIC ARTERY A N E U R Y S M . - - S e v e n t y -

one cases of splenic rupture in pregnancy have been reported in the world literature, 25 since 1957 (26). Trauma is the usual etiology, although spontaneous ruptures of splenic hemangiomas or of infected spleens have occurred. Various mechanisms for traumatic injury have been des~ibed. Splenic rupture may follow blunt trauma to any abdominal area. Automobile accidents are the most frequent cause and, thus, this problem will become more common. Treatment is removal of the spleen and ligation oLb~eding vessels. The maternal death rate is 15.4% and the fetal :~::fi6~th rate is 69.5%. Any pregnant woman .who presents with left Shoulder pain. shock and signs of peritoneal irritation with or without a history of trauma should have an abdominal tap to rule out splenic rupture. Laparotomy should be performed to establish the correct diagnosis when other methods fail. Sixty-two cases of rupture of splenic artery aneurysms in pregnancy have been reported, with only I fetal and 17 maternal survivors (125, 23

202, 221). While uncommon, this lesion seems to be more common in women and, when rupture occurs in pregnancy, it usually occurs in the third trimester. Successful treatment depends on prompt diagnosis, vigorous supportive therapy, adcquate fluid and blood replacement and early operative intervention. Splenectomy and r.esecti~a of the aneurysm is the treatment of choice. Splenic rupture is the most eommon preoperative diagnosis; an intact spleen should raise the suspicion of such an aneurysm. It usually is located along the upper border of the pancreas and may be concealed in a large hematoma. Evacuation of the hematoma and exploration of the area are mandatory. CIRRHOSIS, ESOPHAGEAL VARICES AND PORTACAVAL SHUNTING.

The coexistence of cirrhosis and pregnancy has been rare in the past. This is due to the low incidence of nutritional cirrhosis in women and the usual development of the disease after the childbearing age. However, the increasing occurrence of subclinical hepatitis and postnecrotic cirrhosis may increase the frequency of pregnancy complicated by cirrhosis. Demonstrated esophageal varices c~rry a significant threat of hemorrhage. Although some obstetricians favor termination of the pregnancy even in the absence of bleeding, a pregnant patient with esophageal varices can be brought successfully to term if supervised carefully, ln the event of major hemorrhage, surgical decompression of the portal vcnous system can be performed. O'Leary and Bcpko (157~ described a side-to-side portacaval shunt in 1962. Two end-toside portacaval shunts performed during the second trimester have been recorded since (32, 102). A mesocaval shunt for blecding varices during the fourth month of pregnancy was recently reported by Jochimsen and Castaneda (101). All 4 patients stopped bleeding and delivered viable and normal infants subsequent to the shunt. The mesocaval shunt was chosen because of its ease of performance and the effective decompression possible with the large ana'stomotic stom,~. Leg edema, significant l a t h e last patient's late pregnancy, was not a problem postpartum. However, ligation of the inferior vena cava, which is inherent in the mesocaval shunt, may be a significant disadvantage to this procedure during pregnancy.

CEREBRAL VASCULAR ACCIDENTS

cases of cerebral arterial occlusion during pregnancy have been reported (169). Symptoms depend on the location of the occlusion and the amount of available collateral circulation. Convulsions are rare with arterial occlusion, although they may be: seen with other types of cerebral vascular accidents, l~n most cases, Ilo definite etiology c a n be found, but cerebral embolism ARTER.IAL

O C C L U S I O N . , . . . . Few

24

is the usual diagnosis. An embolus may originate from the heart, particularly with mitral stenosis or atrial fibrillation. Paradoxical embolism may occur through a patent for'amen ovale (45, 185). Amniotic fluid emboli can pass through the pulmonary circulation, and have been reported (4). Thrombosis within a cerebral artery may develop secondary to clotting mechanism changes that occur normally in pregnancy. Treatment should be the same as in the non-pregnant individual. Successful craniotomy with removal of the thrombus has been performed (57). Active physical therapy should be used after neurologic stabilization has occurred. Most patients attain partial recovery. Cesarean section should be done only for obstetric indications. VENOUS OCCLUSION. Thrombosis of one of the cranial venous sinuses is even less common during pregnancy and is a rare complication of the puerperium. Convulsions usually occur and may simulate eclampsia. Treatment is symptonaatic, although operative decompression has been reported (112). I

RUPTURE OF ANEURYSM OR ARTERIOVENOUS MALFORMATION.

Subarachnoid and intracerebral hemorrhage secondary to rupture of an arteriovenous malformation has been recorded 11 times (49). Since 25% of these patients, die in the first 24 hours, prompt diagn~is and treatment must be instituted. Angiography followed by surgical repair is recommended (49). The indications for sterilization, therapeutic abortion and cesarean section remain as obstetric ones. Rupture of an intracranial aneurysm is more common but'is still rare (81, 166, 189). Diagnostic tests and surgical treatment of this catastrophe are carried out as if the patient were not pregnant. Hypothermia has been employed successfully without apparent harm to the fetus (81, 166). Delivery and sterilization should be performed only for obstetric indications. The most common cayuse of intracerebral hemorrhage in pregnancy is eclampsia (112). lit is also the most difficult differential diagnosis. Any patient with convulsions and/or coma, with signs of intracerebral bleeding such as nuchal rigidity, Kernig's sign and localizing or lateralizing signs, requires carotid angiog~?aphy to establish the integrity of the cerebral circulation. If a surgically correctable lesion is found, appropriate operative treatment :~hould be performed. Coexistent eclampsia must be treated concurre~tly,

ENDOCRINE .DISORDERS The endocrine organs are basically a chemical regulatory system. As such, the fluctuations of female hormones in normal menstrual 25

cycles might be expected to influence the activity of these organs. The profound hormonal alterations during pregnancy regularly cause changes jn the endocrineglands. Abnormal function of these organs may occur in pregnancy, but the diagnosis of aberrations must take into account the "normal" changes. Although pharmacologic manipulation usually is effective in controlling the abnormal glandular activity, occasional surgical" management during pregnancy is necessary. Some endocrine lesions, e.g., pheochromocytoma, require operation as a life-saving measure. HYPERTHYROIDISM. Thyroid function is significantly altered by pregnancy. The signs and symptoms of hyperthyroidism are frequently present in pregnant women: emotional lability, tachycardia and excessive perspiration associated with a palpable thyroid gland. The basal metabolic rate (BMR), protein-bound iodine (PBI), butanol-extractable iodine (BEI) and thyroxine (T~) levels are all increased by pregnancy ( 6 , 127, 128, 130, 144, 168). Thyroid-binding globulin (TBG) is elevated by pregnancy (129, 144, 168), whereas thyroid-binding prealbumin (TBP A) is unaffected or slightly decreased (168). Triiodothyronine resin uptake (Ta-resin) and triiodothyronine red blood cell uptake (Ta-RBC) are both decreased by pregnancy (144, 168). Free thyroxine concentration (free T4) is slightly decreased (168). Serum cholesterol levels usually are increased, but.not significantly so (144). I TM uptake usually is not determified in pregnant humans because of possible damage to the fetal thyroid, but is reported to be elevated in gestating animals (6). Despite these changes, most pregnant women are clinically euthyroid. In patients in whom mild hyperthyroidism is suspected, nothing is lost by continuing to watch without specific therapy. There is no evidence that mild hyperactivity of the thyroid is a threat to an otherwise normal pregnancy. ii

i

i

i

,,

T A B L E 2.~COMPARATIVE VALUES OF TttYROID FUNCTION DURING NON-PREGNANT AND PREGNANT STATES THYROID FUNCTION TEST

N O R M A LVALUES

BMR PBI BEI "['4 TBG* TBPA* Tz,resin Ta-RBC Free T4 I TM uptake Cholesterol

--i0to +10% 4.0.7.5 #g.% 3.2-6.5 #g.% 3.2-6.5 #g.% 30 ttg.% 140 ,ug.% 25-30% 11-17% 2.76/0.5 ng.% 40% 216 rag. %

PREGNANCY VALUES

+ 1 5 to + 2 5 6.5-I 1.5

5.5.10.5 5.5-10.5 56 100 I0 10 2.35/0.7 40 231

*Binding capacity of T~, I

I

I

IIU

II I III

26

II I I I

Patients with clinically significant hyperthyroidism represent a greater problem. If maternal disease is allowed to go untreated or inadequately treated, the deleterious effects on the fetus arc notorious; abortion and stillbirths are common, or tile offspring may be born with thyrotoxicosis apparently from placental transfer of long-acting thyroid stimulator (LATS) ( 5 2 ) . Overtreatment with antithyroid drugs may cause neonatal hypothyroidism (216). Propylthiouracil can traverse the placenta and be incorporated into the fetal thyroid (80, I83). Finally, thyrotoxic crisis, a life-threatening situation, may develop in the hyperthyroid pregnant patient, unless treated promptly (93). The incidence of thyroid enlargement in pregnancy is estimatcd to be twice that in non-pregnant women ( 4 t ) . Petri believes symptomatic hyperthyroidism in pregnan6y to be 0.077% (165). At present, there are three forms of therapy available for hyperthyroidism: (1) 11:~; (2) antithyroid drugs; and (3) subtotal thyroidectomy after proper preparation with antithyroid drugs and iodine. I T M therapy during pregnancy should be avoided because 1TM does cross the placenta and after the twelfth week o'f gestation will be taken up by the fetal thyroid. Although I T M has been shown .to be harmful to the fetus (182), several instances of administration of I T M when it was not known that the patient was pregnant have been reported (35). The infants delivered later were normal. These experiences suggest that inadvertent radioactive iodine therapy in early unsuspected pregnancy is not an indication for interrupting the pregnancy. Current drug therapy consists of an antithyroid agent in doses adequate to suppress thyroid function to euthyroid levels over a period of several weeks. At this time, thyroid,replacement, usually triiodothyronine, is started to prevent maternal hypothyroidism. Antithyroid medication is stopped or reduced in the third trimester to mininaize suppression of the fetal thyroid gland. The perinatal loss rate is 9% (84, 95, 165, 168, 2116). With this regimen, symptomatic recurrence after discontinuing the drugs is 50% in the non-pregnant state; it is higher during pregnancy. Some endocrinologists prefer to use propylthiouracil ",.done to maintain the euthyroid state, but recurrence of thyrotoxicosis when the drug is stopped is still higher ( 2 1 6 ) . Medically treated mothers deliver infants who show a higher incidence of neonatal hypothyroidism and central nervous system injury, usually transient (85, 216). Two recent series of patients treated by partial thyroidectomy have renewed interest in the surgicalapproach (73, 7 9 ) . Hawe (79) reported 2 stillbirths in 38 of his own patients and review,; subtotal thyroidectomy in 199 patients who produced 186 live births. Hamil, ton et al. (72) had no ~fetaI complications in 24 patients undergoing thyroidectomy during pregnancy. : Both authors prefer to operate in 27

mid-pregnancy if possible: In fact, if the patient presents late in pregnancy with: thyrotoxicosis, she should be treated medically through labor and the postpartum period (72, 79; 169) Indications for operation peculiar to pregnancy are the prospect of a major obstetric operation late in pregnancy and diabetic or cardiac complications for which early establishment of a euthyroid state may be advantageous. The preparation of the pregnant patient for thyroidectomy is the same as in the non-pregnant condition. Antithyrok~. drugs are administered until-the patient becomes euthyroid. Iodine is given 10 days prior to operation to reduce gland vascularity.. Since maternal hypo.ttiyroidism is so deleterious to the fetus, thyroid replacement must be used as soon as possible postoPeratively: With either type of therapy, the patient must be closely observed. There.are occasional reports of thyrotoxicosis associated with hydatidiform mole or trophoblastic malignancy. Theplacenta probably does secrete a thyrotropic-like material, although it has not been completely characterized (86)..Whenever unexplained thyrotoxicosis occurs in pregnancy, the possibility of a mole or choriocarcinoma must be given serious consideration. HYPERPARATHYROIDISM,- Hyperparathyroidism is caused by excess of parathormone usu~illy due to an oxyphil cell adenoma of the. parathyroid glands and is characterized by hypercalcemia, hypophosphatemia and hypercalciuria, Renal calcinosis, renal stones and chronic pyelortephritis are frequent complications and may be irreversible. Characteristic.bone changes appear on x-ray tilms. Fatal hypercalcemic crises may occur. Neonatal tetany in the offspring of mothers with hyperparathyroidism may give the first clue to the existence of maternal disease. (77). Fetal outcome seems to-be related to the severity of maternal diseasei Stillbirth or neonatal death is extremely frequent when maternal bone disease is present and is rare without maternal bone disease (123, 210). Hyperparathyroidism associated with pregnancy is rare, only 39 or 40 cases having been reported (77). Only two cases have been reported (•80) in which the. adenoma was removed .during pregnancy. However, in view of the high fetal loss in the presence of severe maternal diseasc (217), surgical exploration should not be postponed because of pregnancy. If necessary, exploration must be carried into the mediastinum (3). Modern supportive therapy, shoutd prevent damage to the fetus. PRIMARY ALDOSTERONISM.-,-PrimaryaIdosteronism is an uncommon disease characterized by hypertension, elevated aldosterone secretion rate, subnormal plasma renin activity, hyp0kalemia and normal renal ffihction.. Fifty per cent of these patients have abnormal glucose tolerance curves. It is caused by an aldosterone-secreting adenoma of the adrenal, cortex and is cured, by removal of the adenoma (37). Occasionally, treatment with spironolactone will corn28

pletely suppress the adenoma (16). Corm (37) estimates that 3,000,000 people .with "essential" hypertension in the United States have hyperaldosteronism. Only four cases have been reported in association with pregnancy. In the first (40),. the fetus was lost.with an abruptio placenta during attempts to control the hypertension medicall),. Resection of ttae aden.om'a was done post partum. A second patient (21) was treated by resection of the adenoma. Pregnancy was diagnosed i n the postoperative period and terminated fox" other reasons. The third patient (65) underwent resection of the adenoma during pregnancy and apparently carried the pregnancy to term successfully without further complications. The fourth patient (16) was already being treated with spironolactone when she beca~le pregnant. During pregnancy, this patient improved enough so that spironol.actone could be discontinued until the postpartum period. Since progesterorie causes salt retention, it was hypothesized that enough salt must have been retained durIng the pregnancy to suppress the adenoma. This type of tumor, though rare, should be considered when "essential" hypertension is diagnosed in pregnancy. In patients who have not been taking diuretics, a serum potassium level is a good screening test and hypertension with hypokalemia is strongly suggestive of an adrenal adenoma. If an aldosterone-secreting tumor is a likely possibility, measurement of adrenal vein effluent for aldosterone is the most accurate diagnostic tesI. Egdahl et al. (51) have described the technic of percutaneous puncture or saphenous vein c u t d o w n t o gain access to the inferior versa cava. X-ray localization of the catheter tip must be kept to a minimum. Such a procedure m a y obviate an abdominal exploration in a pregnant patient. Since these tumors usually are small, angiography may, not be rewardJn~;. ~" " ' ", I n t h e absence of preoperative localization, the transabdominal approach should be used so that both" glands can be explored. If the diagnogis is firm and the patient is not improving during pregnancy, as in t h e fourth case above, the adenoma should be resected a s soon as possible during gestation. PHEOCHROMOCYTOMA....... This tumor is a rare, usually benign, tumor of the adrenal medulla or organ of Zuckerkandl which manufactures excess catecholamines from tyrosine. Ninety-one c a s ~ associated with pregnancy have bee0 reported ( 6 0 , 212), with 44 maternal and 40 fetal deaths. ThJs.tumor ma~,~p~esent dunng pregnant) lth sustained hypertenslon md~stmgulsh/abfe from essentml hypertenslon or preecI~mp'.sia or as the classic paro×ysmal hypertensive episodes with normal blood pressure or severe hypotension between attacks. M a n y of these patients have associated hyperglycemia and hypermetabolism. Palpitations, cold extremities and ot,her vasomotor symptoms are common. Excessive perspiration usually is present: Sudden suppression of the catecholamine effects by an alpha•

•

;

\

29

.

•

adrenergic blocking agent such as phentolamine (Regitine) may produce sufficient hypotension to injure the fetus, which may already be compromised. .~Demonstration of elevated catecholamines or their metabolic end-product, vanilmandelic acid ( V M A ) , in a 24-hour urine sample may be diagnostic. The normal level is less than 10 rag./24 hours. Some foods, such as bananas, can invalidate the test. Since these tumors generally are large and vascular, selective angiography ,will often localize the lesion if an intravenous pyelogram does not. Care must be taken during injection of the radiopaque dye, because sudden l~ypertension followed by a precipitous fall in blood pressure is frequently seen. Definitive treatment is total extirpation of the tumor, and both Walker ( 2 1 2 ) a n d Fox ( 6 0 ) b e l i e v e that this should be done as soon as the diagnosis is established. Preoperative preparation and appropriate intraoperative monitoring are the keys to successful removal of the tumor. Phenoxybenzamine (Dibenzyline) should be given orally in increasing doses'until the patient is receiving 4 0 rag. three times a day. By gradually raising the amount ingested, hypotensive crises are avoided. The patient is Urged to drink an extra volume of fluid, and occasionally intravenous administration of a balanced electrolyte solution will be necessary as the vascular bed expands (38), When a stable, a n d usually normal, blood pressure is reached while ~ e patient is on alpha-adrenergic blockade, she is ready for operation. An indwelling arterial needle for direct, continuous recording of blood pressure should be used in all patients. Halogenated hydrocarbons, particularly halothane, are the anesthetic agents t:~f choice,, because they tend to cause less release of catecholamines during administration (38). A transabdominal approach is preferred because 10% of the tumors are bilateral and 10% are extra-adrenal. Despite adrenergic blockade, tumor manipulation should be minimal. Occasionally, malignant tumors occur, and if the tumor cannot be resected in toto, the bulk of the tumor should be resected to reduce the amount of liberated catecholamines. With proper preparation before operation, the need for vasopressor medication postoperatively has been-virtually eliminated. A high index:of suspicion and careful evaluation and management should lead to the correct diagnosis and a maternal and fetal survival rate higher than that quoted in the literature 52 and 56% respectively.

CANCER IN PREGNANCY,,, SURGICAL ASPECTS

An abundance of literature i s accumulating dealing with the problems surrounding cancel in-the pregnant patient, or pregnancy in the 30

patient with cancer. While any malignancy can be "present in the pregnant patient, it has not been until the past several decades that such great.attention has been given to this combination of conditions. The most important reason for this is the fact that maternal 'mortality and morbidity from such obstetric complications as toxemia of pregnancy, hemorrhage and infection have progressively decreased to a point at which it is unusual to see death from these complications of the properly managed pregnancy. Although the incidence of the association of cancer and pregnancy may not have increased absolutely, its relative importance has become more apparent. At the same time~ increasingly sophisticated methods of diagnosis have made it possible to detect many cancers early or even in incipient stages of their dcvelopment. More adequate treatment methods have lowered the mortality rate from most neoplasms, making it even more important that they be diagnosed as soon as possible, whether the patient is pregnant or not. All these'factors combine to make cancer in pregnancy worth increased consideration. All too often the only time a young woman is subjected to a com~,~e physical examination is during her pregnancies. Any sust~icious lea~:.:',.:l must be thoroughly, investigated. The most common cancers in women of childbearing age are those of the cervix, breast, thyi*bid and, more infrequently, the gastrointestinal tract. All of these areas can be evaluated by relatively simple means. Changes in some tissues, e.g., breast and cervix, coincident with pregnancy may obscure the physical findings; but this does not lessen the obligation of the:physician to establish a firm diagnosis for every suspicious lesion or symptom. The importance of a firm diagnosis of any suspicious mass or persistent symptom ~canno{ be .stressed too stror~gly.. Just as a m a s s in the breast deserves excisional biRpsy and histotogic scrutiny in the nonpregnant state, so it does in pregnancy,: A single nodule in the thyroid gland, enlarging as it may be during gestation, requires diagnostic evaluation..If it is " c o l d " and single, on scan, biopsy, is imperative. Persistent epigastric discomfort or constipation, particularly when they do not respond:to the usual medications, may be the harbingers of a gastrointestinal malignancy. Vaginal s p o t t i n g may herald a threatened abortion or be the first sympt,om o f carcinoma of :the .cervix. T h e physician must maintain a high index of cancer consciousness and ignore the pregnancy wllile assessing the situation. T h e increasing awareness of cancer as a problem during pregnancy has produced a n enormous flow of papers a n d reports. A n a t t e m p t is made h e r e to select .representative studies concerned 7.with surgical aspects of cancer in pregnancy, and to synthesize some ~general guide, lines about the diagnosis and treatment of the more common cancers associated .with pregnancy.. Specific data about the effect of pregnancy on themalignancy, and the reverse, will be. indicated, 1

3]

THYROID CANCEI~..--While carcinoma of the thyroid during pregnancy is not common, Betson and Golden ( 1 5 ) reported 7 cases in a series of cancers ~lssociated with pregnancy, making it the third most common tumor in their group. Breesc ( 2 3 ) , in a report of 217 patients under the age of 45 with carcinoma of the thyroid, found 16 who were pregnant at the time of diagnosis and 44 who had been known to have thyroid tumors during onc or more pregnancies, but had not had the diagnosis made or treatment initiated for at least 6 months following pregnancy. Friedman (62) points out that the increased metabolism of the thyroid gland in pregnancy may enhance the probability of cancer developing at that time. The primary therapy for carcinoma of the thyroid is thyroidcctomy. Since the pregnant woman who might develop a thyroid malignancy is generally young, this discussion will be limited to papillary or follicular carcinoma. Controversy still highlights thc preferred proccdure even whcn not complicated by a pregnancy. The minimal surgica! procedure is thyroid lobectomy. Whether neck dissection is employed in addition depends on the surgeon's philosophy regarding the discase. If indicated by the presence of involved lymph nodes, then a ncck dissection should be undertaken. Radioactive iodine has no place in the primary treatment of thyroid malignancies and it should be avoided during pregnancy because of its documented effects on the fetus (181). However, it can be useful in the management of metast,'fses of thyroid tumors, particularly the papillary variety. All observers agree that postoperative thyroid supplement is essential to delay or prevent rccurrent disease. Some basic questions regarding the problem of thyroid carcinoma and pregnancy revoivc around the effect of e a c h condition on the other. The concurrence of the two is so infrequent that statistically valid conclusions cannot be reached from review of the-literature. Friedman (62) cornpilcd the answers to a questionnaire on this subject and came to the following conclusions: "The consensus holds that pregnancy concurrent with carcinoma of the thyroid has no adverse effect on the prognosis of the disease, nor does pregnancy subsequent to treatment alter the cure rate. Therapeutic abortion is usually not advocated for either concurrent or subsequent pregnancy. Nevertheless, waiting a varied period of time after treatme.nt of the thyroid malignancy before undertaking pregnancy is advised." CARCINOMA OF THE DIGESTIVE TRACT.--While carcinoma of the

rectum and colon is increasing in signiticance throughout the United States, there are few rcportcd cases associated with. pregnancy. In 1962, O ' L c a r y and Bepko ( 1 5 7 ) were able to collect fewer than 100 cases from the world literature, with an incidence varying between I in 50,000 pregnancies and 1 in 100,000 pregnancies. The true incidence is unknown bccause of the sparsity of reports (140). Tumors 32

of other portions of the gastrointestinal tract have been reported only sporadically. Management of these tumors in pregnancy is the same as in the non-pregnant state. The gravid uterus will cause variations only in the mechanics of the handling of the bowel, not in the principles. Undoubtedly the greatest difficulty resides in tile diagnosis. The patient should be questioned about symptoms, and those that do not respond to the usual measures must be investigated. Pernicious vomiting, persistent epigastric distress, unrelenting constipation, crampy abdominal pain or rectal bleeding cannot be disregarded. Proper diagnostic tests must be conducted whenever any suspicion of an underlying malignancy exists. Early diagnosis will lessen the tragedy of a lesion rendered incurable by neglect. O'Leary et al. (159) state tt'at Whenever a rectal lesion is suspected, proctoscopy and barium enema are essential. The proctosigmoidoscopic examination can bc done easily, even in late pregnancy, with the patient lying on her right side. Therapy is based primarily on wide extirpation of the lesion. In a recent review, Barber and Brunschwig (11) outlined their treatment of cancer of the lower large bowel occurring during pregnancy. During the first trinacster, the malignancies are removed as in the non-pregnant individual. The ovaries, tubes and uterus are resected as dictated by the findings at laparotomy. From 12 to 20 weeks, they advocate routine hysterectomy to provide better exposure and ensure adequate margins around the tumor. Oophorectomy is recommended for all low-lying colonic cancers, because of the high incidence of metastasis to the ovaries. O'Leary et al. ( 1 5 9 ) do not believe that the uterus needs to be removed during these weeks unless it is involved by the tumor. When the fetus has reached the stage of viability, the management is again relatively straightforward. The infant should be delivered via cesarean section to prevent trauma to the tumor. Abdominoperineal resection or a low anterior procedure is then performed with or without hysterectomy, depending on local conditions. Tile 20- to 28-week period has always presented a controversial problem. B S:rber and Brunschwig allow the pregnancy to go to the stage of fetal viability and then proceed accordingly. O'Leary et al. believe that with adequate exposure the malignancy can be removed without unduly disturbing the uteruS: and its co~atents. That the pregnancy can be ignored and the pa~iei~t :treated as at any: time is welt demonstrated by the case of Finn and L o r d (56). A woman in h e r sixth month o f pregnancy presented herself with acute colonic obstruction secondary to a sigmoid carcinoma. She underwent, successively, a decompressing transverse eolostomy, a curative resection of the sigmoid, closure of the colostomy and delivery per vaginam of a 3,360 Gin. infant. Again, it appears that, except for the patient who 33

is close to term, when simultaneous cesarean section should be considered, the pathologic condition should bc treated :is though the pregnancy were not present. Individual case reports of such tumors as rcticulum ceil sarcoma of the duodenum (82), argentattinoma of the appendix (188), primary malignant lymphogranulomatosis of the stomach (187) and others (133, 155) have been reported. These tumors, like carcinoma of the stomach, are difficult to diagnose because their symptoms mimic those ot' pregnancy so closely. Once the diagnosis is established, wide excision of the tumor is the proper treatment..:Interruption of, or interference with, the pregnancy should be done only when it is made necessary by inv'olvement of uterus, tubes or ovaries by the {ttmor. Whether pregnancy adversely affects malignancies of the gastrointestinal tract always poses a problem, in a report of 4 cases of abdominoperineal resection during pregnancy, Bacon and Rowe (8) reviewed the literature prior to 1947. Of 72 cases of rectal carcinoma occurring during pregnancy, 24 were inoperable and only 35 underwent curative resection, with a 15% fetal loss and a 10% operative mortality. On the other hand, Warren (214) reviewed 1,600 cases of rectal cancer seen at St. Mark's Hospital in London. Only 9 cases occurred during pregnancy; all were resected, and 6 of the 9 were long-termsurvivors. We favor the more optimistic views., l)elav in diagnosing the malignancy and not the pregnancy is the culprit in pre.,vious distieartening results. MELANOMA.---As with other tumors, there has been consid.erable speculation concerning the effect of pregnancy on malignant mela.noma and vice versa. The pigmentary changes that occur during pregnancy are well known. However, the incidence of malignant melanoma developing during pregnancy is difticult to establish. Pack and Scharnagel ( t 6 1 ) quote Cosgrove as having 3 s u c h cases in 122,000 pregnancies. In their group of 1,050 patients with malignant melanoma, 32 were associated in someway with pregnancy. Similarly, George et al. (163) reported on 115 patients who were pregnant sometime during the course of this disease, 77 prior to or during the treatment and 38 subsequent to treatment. White et al. (218.) described another 30 patients who had melanoma either during their pregnancy or within the 5 years immediately following. All patients were treated by ..radical operation wide excision, and lymph node dissection where indicated. In no case was there evidence that the pregnancy played any role in prognosis or had any effect on treatmerit. Shocket and Fortner (191) studied pregnancy in the hamster afflicted with transplanted hamster melanoma and found that pregnancy had no effect on the growth or metastasis of the tumor. All these data indicate that melanoma during pregnancy should be treated exactly as it would be in a patient who is not pregnant. Thera34

pcutic aborl.ion or" avoidance of pregnancy in the ftlltlrc is l~.ot warranted ( 2 1 8 ) , except ns one is intluenccd by the uncertain life span of the mother. Survival of pregnant paticnl.s is as good as th:.tl i~l the n o n - p r e g n a n t group when classified by extent of ~!le mcl.antm~.a. The only excel~lion is lhc possibility of earlier regional lymph node involvement in the pregnant group rc .w,rted by O~.osgc el a/. Pcrhap'.~ prophylaclic measures during pre.gnancy play a larger part in m e l a n o m a th,..~a' ' in many.. ¢)thc~'" tumor::. Pack suggests. . cleclive or prop!~ylactic removal of pigmentt:d moles in pregnant v¢o~en trader the following circumstances' ( 1 ) n~olcs on lhc lrunk subjecl to irriI.atior~, and all m+~lcs, " <.)n the genitals and feel; (21. moles thai arc smooth, blue-black, or dark t.zov, n ", , ' ' ( 3 ) ~nolcs :'" that e×hibil increased pigmentatior.~, elevation or enlargement in diameter, ~ r arc associated with ulceration pain or .flct:dzng. In this manm..r, it may bc possible to prcvOnt the devciopnmnt of m:alignancy in a lesion ~.thcr ~ ~' w i's e ~ l i k e l y to become cancerous. (...ARCINC~MA O!: Till" BI¢.EAST.~ I W(: ' : " "' ' ~; r~~ust be d~scussed. " .... :' assoc~atum, First, the coexistence of pregnancy ~r lactation with b.rcast c~mcer and, second, the occurrence of pregn~ncy at some time .following Ireatment of breast cancer. The prognoslic sig.nilicallce dill'ers greatly in these two groups. . In the l'orn~er jn..l.ance, " s ' "' there may be a. sig,tificant delay in diagnosis duc to the breast changes occurring with presnancy .or l,.lctat~on. In the latter situation, natural ,.e.lcct~ n destines those patmnts with the mcrc aggressive tumors ~o ,.,,uccumb before achieving pregnancy. Thus, only i.he better-risk patients ate exposed. "l"l.~cre have been a n u m b e r of excellent reports concerning the problem of breast cancer compl~catln,., pregnancy ('~8, 70. 76, 87, 91, 175,. 205, 219, °20)..,_ . Mosl. of these' quote and con<."' u r with the incidence figures given by \Vhitc in t 9 5 5 ( 2 1 9 ) . In .that review, hc .points out thal. one cm-~ exi_ect - ~-" to scc about: . three brea.~{ . - s cancers per 10,000 pregnancies~ and an iqcidence of pregnm~cy of 2 . 8 % in patients with t:reast'~ ~" " ' cancer. When patients in the childbearing age are separated out, it c',p be stated that one-third of tho..c wil:h breast can c e r ( l u r i n g t h a t perle -' "~" • ~pl i cation ~" . cl will have pregnancy as a con All authors agree that there is no real knewledge conce,'ning the effect 6~'the varying hormot:ms of pregnancy on the growth a~d de...., velopment of breast c,mcer. Ho~; e er. there does seem to be a higher incidence of advanced disease,,~manifest by lymph node metastases, in the pregnant and lactating ~'ornan when c o m p a r e d to the nonpregnant w o m a n , ht.the~, tht,..,s a result ot d~tlerenc.c in biologic potentiM, direct effect of hormorm,.'s or effect of delay in d~agnos~s", is not entirely clear. T h e latter factor probably is the m o s t important. B u n k e r and Peters ( 2 8 ) noted that in less than 3 0 % of their c o l 9

"

'

'

i~

• '11

"

•

.

"

¢,,.I 1

S"

'

.

V,~V~

~

~"

"O

r,

.

'

lected

cases

of

breast

cancer

in p r e g n a n c y ,

the definitive

""

diagnosis

was m a d e and treatment carried out within 3 months of the time ~t 25

mass was discovered in the breast, They also noted that the best survival was in the group lirst observed and trcatcd during pregnancy when compared lo those first observed during lactation. However, this survival ~as only half as good as that in the group whose cancer was evident prior to pregnancy. These data certainly point toward a delay factor in the outcome of such patients. In a similar vein, Holleb and Farrow (91) pointed out that of their 283 patients, 193 were considered operable ( 6 8 % ) , 73 were inoperable and 17 had been t~eated adequately elsewhere. Of the oper~able patients, ' "" ' however, 79% had positive axillary nodes and of ihe inoperable pdli~nt.s ' ",. all we/:.e dead within 4 years. This indicates 0aat delay in diagnosis, or some other fador, makes the pregnant patient with brc,"~st" cancer a worse risk than a non-pregnant individt, al. There has been a change in the attitudes of some authors over the years about the proper treatment of breast ,.ant.~.z "' "'" during pregnancy. Haagensen (70) recently reviewed the literature and discussed his criteria for treatment. He stated that some years ago he had oF,posed the operative treatment of breast cancer during pregnancy because he believed that the chance of survival w'as' so poor that radical operalion was not warranted. However, in the light of larger series and more recent results, he now believes that patients who are in the operable category shot~ld be treated by radical operation at the earliest possible opportunity. T h i s belief is supported b> all other authors reporting larg~ series. Thus, there is unaninaity of opinion regarding the p,'imary treatment of breast cancer during pregnancy. While there is considerable discussion regarding the management of the pregnancy in these patients, the consensus is that interruption of pregnancy offers no significant advantage regardless of the stage of pregnancy during which the rumor is discovered. Holleb and Farrow (91) b.lle'~c, e "~, ,* that if the patient has far-advanced disease, she should have therapeutic abortion and prophylactic oophorectomy. While they have not produced any long-term survivors with this therapeutic regimen, they argue that the patient's terminal period is more ccmfortable"r • - and more.s"atisfactory without the added burden of pregnancy and the subsequent newborn infant. In general, the religious, moral Jmp,lca-: ~" "" " and ~ . o c J"'" al tions, as well as the background of the patient, should be and often are the deciding f a c t o r s . Because of the high incidence of lymph node metas asls. the reported 5- and ]0-year survival figures are discouraging. In a study of 41 patients, 10 years or more following treatment, Haagensen relates survival to clinical stage. In the early-stage patients without positive nodes, the I0-year survival was 62.5% as compared to a 70% 10-year survival in the non-pregnant group. However, in the o ~ t',:' later-stage group, the 10-year survival was tess than I,:...-;~ as compared to 1 8 - 4 0 % in the control group. Holleb and F a r r o w report a 36

5-year survival rate of 21% of those patients with posit'~vc nodes as compared with 58% of tile patients with ncgalivc nodes. Unfortunately, 72% of the patients had posJtJv,~ " " ,~ m3dcs.. Hollcb and F:lrrow were unable to report any difference ia survival in patients whose pregn'a.ncm.-'*.s. were. terminated . . (one-laalf the cases). As previously noted, they reported tilat all patients who were primarily inoperable were dead within 4 years. Termination of pregnancy in 7 of these patt..nt., had no effect, as riley were dead within 2 years. In a previous study of young women with breast c,tncc~, Irc.vc, vnd Hollcb (205) reported a 5-year survival of 30.7%. in 54.9 women under 35 with breast Cancer. Of those who were simultaneously pregn~,nt, the survival rate was only t 7 . 9 % , whereas those who became pregnant subsequent to the radical mastectomy had a 5-year ,;urvival rate of 5 6 . 7 % . This, again, reflecl:.~ natmal selection Ire c. and Holleb were unable to determine any effect of therapeutic a b o f tion. These survival figures are fairly typical of those reported by others (75, 175, 220). However, i.a, a recc~ • 'r~t review of patients under 35 w,itt~ breast malignancies, Horslcy et al. (9,1.) described i7 patients who were pregnant or immediately post partum. Five of tl)ese patients were no{ operated on; all I2 of the remaining patient, • "~ s survived 5 years, and 10 of the 12 were long-term survivors. The treatment was radical ~nastectomy, and 5 patients received postoperative irradiation. Eight of the 12 specimens had positive axillary nodes. These reports are encouraging and once again stress the need for early diagnosis. Since this is the only aspect ~.ff the disease the physician can alter, any brea:st nodule must be exramined histologically. If cancer is found, radical maslectomy must be undertaken promptly. Despite va~atJ.on of ot~inh)n over t"t 1.c"~ 0years, it is now the consen"# " sus that pregnancy subsequent to the treatmen{ for breast cancer is without adverse affect. Some belie c that pregnancy should be allowed only to those who had p,cgat~ve nodes. Ol]crs believe that any patient who has surviveo-several years will be able to tolerate p~"egnancy without affecting, the malignant process. As f.greviousl"3 noted, those patients with aggressive disease will succumb prior to the advent of subsequent pregnancy, and, therefore, the long-term picture for those who become prce, nant following treatment for breast cancer is relatively good, .fnere is no evidence to suggest that abortion should be considered i n s u c h p,,hent": ~' .... s Although experience with bj:ea~st cancer in pregnancy is limited at the University of Kentucky, the general policy is to treat t m cancer as mdtcated and not interfere with t h e pregnan,-3. ' " , Abortion h a s . n o t •

been those tients for 2

"~

.

~V'~S

p e r f o r m e d o n such patients and o v a r i a n :ablation. is limited to in w h o m recurrent. or " -~'~ .develops. . . . . Y o u n g .p a . metastatic . . d.lscase w h o h a v e been treated for breast cancer .are-advised t o wait years before a t t e m p t i n g pregnancy, If their cancer involved 37

nodes, it is recommended that pregnancy should not be undertaken. Non-hormonal birth control methods are those recommended. In summary, breast cancer associated with pregnancy occms in about 3.8 per 10,000 pregnancies, and pregnancy can be expected to occur in about one-third of the patients in the childbearing age who have breast cancer. When diagnosed during pregnancy, the over-all survival is less satisfactory than in the non-pregnant state, primar!ly because there is a higher incidence of advanced, metastatic disease. Whether this is a function of delay in diagnosis or the effect of pregnancy on the tumor in these patients is not yet known. Treatment is directed at the ca.ncer as if the woman were not pregnant, and interruption of the pregnancy is not warranted. This entire attitude was well stated by Byrd et al. (29) after their rev.;ew of this problem as seen at Vanderbilt" "In the face of general enthusiasm for terminating the pregnancy, we believe the evidence is that 'the cancer should be terminated." CARCINOMA OF THE CrRV;X. Pregnancy affords the physician an opportunity to screen many young women for cervical cancer and its precursors. The aovent of the Papanicolaou smear opened the era of diagnosis before the existence of an apparent lesion. Unfortunately, a large number of women never find their way to a physician's office or to a clinic for proper evaluation and screening. However, the ~eatest proportion of pregnant patients do seek medical care at some time during their pregnancy. It is during this prenatal evaluation that each patient should be examined for any evidence of cancer, and, in particular, a Pap smear and adequate visualization of the cervix should be done. As a result, the seemingly increasing problem of cervical cancer, particularly in younger women, ultimately will be solved. CARCINOMA-IN-SITU. Although the entity of carcinoma-in-situ was described many years ago, the diagnosis has become generally accepted only in the past two decades. In the case of the pregnant patient, there has been considerable confusion and conjecture regarding this diagnosis until recently. In 1953, Greene et al. (67) discussed preinvasive carcinoma of the cervix during pregnancy and demonstrated the lesion in 14 pregnant patients. The patients were followed through pregnancy and the puerperiurn, and, in 12, similar lesions were again found in biopsy or operative specimens. Greene and his associates concluded that the lesions were not pregnancy changes as previously believed by others. The same authors (68, I62) discussed other abnormalities of the cervical epithelium related to pregnancy and increased the number of patients with pregnancy associated with carcinoma-in-situ with proved persistence. These reports, along with others, have gradually convinced even the most dubious observer, so that now the diagnosis of carcinoma-in-situ dur28

ing pregnancy is relatively commonplace and many reports have appeared in the literatqre. "File reported incidence of cervical carcinoma-in-situ associated with pregnancy varies widely. Incidence figures of 0.49% .(134) and 0.1 l% ('~v0)__ are not unu~ual..~ ~ On the other hand, tile incidence of pregnancy in patients with carcinoma-in-situ of the cervix may rersch as high as 9.3%. Diagnosis generally is n',~de in the asymptomatic patient by the Papanicolaou smear. Any suspicious cells in the smear must be followed up by adequate tissue study. Whether or not one performs multiple punch biopsies or conization of the cervix is a matter of personal preference. Jones et al. (103, 104) demonstrated that multiple punch biopsies are quite effective in the differeotiation between in-situ and invasive carcinoma during pregnancy. They believe that complications such as bleeding and premature labor are considerably less frequently seen than with conization. Others, however, believe that, in order to rule out invasive cancer, formal conization must be performed. Unfortunately, most operators take a far less sufficient cone in the pregnant than in the non-pregnant patient. Late .in pregnancy, with any de~ree of effacement of patulousnc, s of the cervix, adequate conization is impossible. However, most authors still believe that this is the method of choice, especially in the middle trimester of pregnancy. The cone specimens should be examined histologically in multiple blocks to rule out the rare possibility of concurrent invasive cancer and carcinoma-in-situ. Management of the patient with carcinoma-in-situ is strictly surgical. There has been considerable change in the past 20--25 years in the definitive treatment of this lesion. At the outset, it was believed that once the diagnosis was established, immediate hysterectomy should be done regardless of the length of gestation. Shortly it was realized that such drastic action was not warranted, and the patient with proved cervical carcinoma-in-situ was allowed to go to term, at which time cesarean hysterectomy was done. Even this relatively radical method of treatment bec~me obsolete rapidly; the patients were allowed to deliver either by cesarean section or vaginally with definitive treatment of the cancer post partum. More modern concepts preserve the childbearing function, provided the smear remains normal following conization ( 6 6 ) . Such patients are allowed to deliver from below and must bei.::f%llowed at regular intervals. When one does a hysterecto~n2¢ in patients with carcinoma-in-situ, either aI the time of or after delivery, simple abdominal or vaginal hyster~ectomy with the inclusion of a wide vaginal cuff is all that is required. No need for wide excision or lymphadenectomy exists. INVASIVE CANCER OF THE CEll.VIx.--Numerous reviews on the sub:39

ject of invasive carcinoma of the cervix during pregnancy have appeared in tile past few years (108, 110, 145, 167, 178, 195, 21 I). The incidence varies with tile clinic and tile area of tile country reporting. Figures from indigent population, show a high incidence, whereas those from ecoilomically favored populations are considerably lower. This corresponds to tile incidence figures in the nonpregnant population. The diagnosis of invasive cancer of the cervix is too often delayed during pregnancy ( I 1 5 ) . The physician confronted with a pregnant patient who has vaginal bleeding is frequently reluctant to undertake a pelvic examination for fear of producing premature labor or a,a abortion. Since bleeding or abnormal discharge is commonly the first symptom of invasive cervical cancer, only proper identification and early d~agnos~s", "'" of tile malignancy, can offer tile .patient any hope for recovery. The prognosis for invasive cervical cancer during pregnancy has long been considered worse than in tile non-pregnant woman. As with carcinoma of tile breast, this difference in prognosis probably is not due to any biologic difference in tile behavior of the disease, but ratller to the delay in diagnosis. If the dlagnosl~ "' "s is suspected, inlmcdiai:e speculum examination and biopsy of any visible lesion must be done. If no lesion is visible, a cytologic smear may demonstrate atypical cells, indicating further study. It should be remembered that in the presence of grossly necrotic lesions, Pap smears frequently do not show cancer cells because of the overabundance of debris. All suspected lesions o/ the cervix should be subjected to biopsy examination. Whether tile diagnosis of invasive cervical carcinoma has been made by biopsy or conization, treatment should be begun imnmdiately. The choice of surgery or irradiation is a matter of preference. However, it is becoming increasingly apparent that the operative management of invasive cervical cancer during pregnancy probably is superior to radiation therapy, at least: in the earlier stages of tile malignancy (108, 145, 178). Whether the irradiation is less effective during this time because of the large uterus and its contents or the postpartum slough and infection is unclear. Surgical therapy of invasive cancer of the cervix includes radical hysterectomy and pelvic lymphadenectomy. The basic principle involved in tile radical hysterectomy is wide excision of parametrial tissue from the paracervical arid paravaginal areas to the pelvic wall, in order to eliminate the primary area of spread of cervical cancer. At the s a m e time, the upper half to one-third of the vagina is sacrificed. Pelvic lymphatics and nodes tip to the bifurcation of the aorta, including those of obturator, internal and external iliac arid the deep pelvic chains are included in the dissection. This operation can be done at any time 40

during pregnancy, and with due care excessive blood loss need not be a problem. The edema of tile tissues and easy visibility of blood vessels make dissection relatively simple, and tile increased blood supply probably improves healing. Advantages of surgical therapy include preservation of ovarian function wilh better preservation of sexual function, relative shortening of the period of therapy and avoidance of secondary radiation problems. On the other hand, certain disadvantages exist. The danger of greater blood loss exists, the technics are difficult in all but the most experienced hands and some complications are inherent in the surgical procedures. However, when these factors are weighed again,:.z the superior results obtained, most gynecologic oncologists now believe that operative therapy is preferable to radiation in tile pregnant patient with invasive cervical cancer, if radiation therapy is chosen early in 'pregnancy, one must either perform a therapeutic abortion or give external radiation and allow spontaneous abortion to occur. Later in pregnancy, a hysterotomy should be done prior to external radiation therapy, which causes sufficient involution of the uterus to allow proper application of radium implants. These general principles are followed at the University of Kentucky in the management of the pregnant patient with the abnormal Pap smear or the cervical lesion: In tile former case, four quadrant biopsies are taken which will usually reveal either severe dysplasia or carcinoma-in-situ. In these cases, conization of the cervix is clone, preferably in the middle trimester of pregnancy. This conization is somewhat shallower than that (tone in t:he non-pregnant patient. Careful examination of tile cone specimen to rule out invasion is followed by watchful expectancy, vaginal delivery at term except for obstetric complications, and subsequent treatment depending on the age, parity and desires of the patient. In the young patient with persistently normal Pap smears, future childbearing will be allowed. In the older multiparous patient with carcinoma-in-situ, hysterectomy is recommended at 4 months post partum. Slmuld the Pap smear, biopsies or cone prove invasive cancer, radical hysterectomy is performed immediately without regard to the stage of gestation. Unfortunately, the over-all prognosis for invasive cervical cancer dur, ng pregnancy is not good. This probably relates to delay in diagnosis with attainment of a late,st{~ge of disease. There is no good evidence that pregnancy itself cause~ any biologic change in the cancer. Occasionally, a patient with stage I disease will have spread outside the pelvis (e.g., periaortic nodes). While lymph node metastases are present irt about 13-1.5% o f all patients with stage I carcinoma of the cervix, such metastases generally are limited to the pelvis. Whether increased vascularity in the pregnant patient allows more rapid or 41

earlier lymph node metastases has not been determined. It has been said that if a pregnant patient delivers through an invasive cancer of tile cervix, the prognosis is hopeless. This apparently is not the universal experience, because some observers advocate delivery from below in patients whose invasive cancer is found at term. The prognosis is not altered provided adequate cancer therapy is undertaken promptly after delivery. The poor results seen previously were more than likely. due to the fact th'a.t the diagnosis was not made at: the time of delivery. Such a patient might then complain of excessive discharge for several months before the underlying malignancy is recognized and treated. Again, delay in dmgnosls " "" and not birth canal trauma must be indicted for the unfavorable results. In summary, it can be said that pregnancy affords an opportunity for the early diagnosis of cervical cancer, and with prompt and adequate therapy results can be expected to be excellent. On the other hand, if a pregnant patient with cervical cancer is not evaluated properly, she can be expected to proceed to an early death. OTHER CANCERS COMPLICATING PREGNANCY. Almost any type of cancer, genital o r non-geni, tal, has been reported in association with pregnancy. Conversely, any woman of the childbearing age who has a malignancy may become pregnant. While reviews by Boronow (20) McGowan (138, 139) and Barber and Brunschwig (10) have emphasized the concurrence of neoplasia and pregnancy, few cases of ovarian (14, 69), vulvar (10), bone (138), soft tissue (31), lymph node (77, 83) and brain (174) tumors occurring during gestation haveappeared. In general, the consensus of these reports is that any patient with a malignant disease who is also pregnant must be treated appropriately for the cancer re'gardiess of the pregnancy. The gravid uterus may alter the mechanics or timing of procedures. If a patient with mediastinal or abdominal Hodgkin's disease requires radiation therapy, ports may be slightly changed and uterine shielding must be adequate. A patient who is found to have a vulvar cancer at term may be allowed to deliver before definitive therapy for the tumor is undertaken. Diagnosis of an ovarian cancer ,no3 be confused by the enlarging uterus, while the retention of fluid during pregnancy may lead to a diagnosis of a brain tumor earlier than might be expected in the non-pregnant state. In summar3,, cancer associated with pregnancy is assuming an increasin~y important role..While the pregnancy makes the patient seek a physician, malignancies are still being overlooked either because of a low index of suspicion, an inadequate examination or lack of evaluation of symptoms. All these factors lead to a delay in diagnosis that is probably the major cause o£ the poor results reported in the man42

agement of various carcinomas during pregnancy. More recent reports indicate that early diagnosis and prompt, approl)riate therapy disregarding the pregnancy can give as good survival figures as in nonpregnant women. Therapeutic abortion in thFse cases is being discarded. Obviously, a tumor of the genital tract or extragenital pelvic organs may require hysterectomy to accomplish an adequate cancer operation. The concept of eliininating the pregnancy to improve the outlook of patients with concon~tant cancer is no longer valid. Equally invalid is the belief that a patient who has been treated for a malignancy should for oncologic reasons not become pregnant. If sufficient time has elapsed to ensure a reasonable chance of cure, pregnancy may be undertaken.

CARDIOTHORACIC SURGERY TftORAClC SUP.GERY.--Thoracic lesions during pregnancy are pre-

dominantly of a rnedical nature and require non-operative management The need for operation in chronic lung infections such as tuberculosis is declining signiticantly and this is now a rare problem during pregnancy. However, pregnancy is not a contraindication to whatever thoracic surgical procedure is needed. Tarnoff et al. (203) reported on 29 pregnant women who underwent major thoracic procedures consisting of two pneumonectomies, eleven lobectomies, eight segmental resections, five wedge resections and three miscellaneous procedures. There were no maternal deaths, and 1 stillborn after a pneumonectomyo Trauma to the chest should be handled during pregnancy as it would be in the non-pregnant state. Avoidance of hypoxia is essential. One troublesome condition, often aggravated by pregnancy, is diaphragmatic hernia. Hiatus hernia is the most frequent variety and usually requires only symptomatic tlierapy .... antacids, small, frequent meals and elevation of the l!ead of the bed. The complications are treated Operatively, on appropriate indications, but operative management is rarely required during pregnancy. Traumatic or congenital diaphragmatic hernia presents another order of difficulty. As t h e pregnancy progresses, more abdominal contents enter the hernia and b ~ o m e more vulnerable to str'angu!ation. In.a 1951 review, Penman (1 64) found 13 instances of strangulated diaphragmatic hernia, all of the Bochdalek type. Eight of these patients died! Although successful repair of strangulated diaphragmatic hernia during pregnancy has been reported ( 2 2 ) , it would seem that the higl~ mortality rate reported by Penman would dictate elec43

Alive Alive Alive Alive Alive Alive Alive Delivered 6 too. postop.; died 4 days post partum Alive Alive

Initial v a l v u l o t o m y Aortic vaivuloplasty Closure of VSD Closure of VSD

Second Second First First First

Collins et al. (36)

Meffert and Stansel (141) First Second

First

Second First

Rheuma!ic ;tortic stenosis Rheumatic mitral stenosis

Ostium primum defect: cleft mitrai valve Rheumatic mitral stenosis Ostium secmidum defect

Second Second

Rhcumatic mitral stenosis Rheumatic mitral stenosis

Kozam eta!. ( 111 ) Mannix and Mahajan (132)

Zuhdi et al. (223) Jacobs et a!. (98)

Lee a L~d Pate (118)

Closure of defect; suture of valve leaflet Mitral valvulotomy Closure of defect

Mitrai valvulotonly M itral valvuloplasty; left atrial thrombectomy Aortic valve replacement M itral valvulop!asty

Alive Alive

Alive Alive

Alive

Abortion Abortion 1 mo. postop. Alive Alive Alive

Alive Alive

Postop. abortion Alive

9

Anomalous pulmonary venous return VSD Repair of traumatic aneurysm aortic arch Rheumatic Initral slenosis Congenital aortic sicnosis VSD VSD

Kay and Smith (107)

Alive

Aortic valvulotomy

Second

Congenital aortic stenosis

Lcyes et al, (120)

Alive

First

Complete correction

Alive Alive

I n fa at

Closure of VSD Excision of aneurysm

OLYICOME

Died postop.

Mother

Corn plete correction

OPERA'FION

Abortion 3 mo. postop. Delivered:at term; died 4 mo. Died postop.

TRtMES'rER

PREGNANCY

Triad of Fallot

DIAGNOSIS

Dul3ourg et al. (47)

AWfltOR

TABLE 3 . ~ O P E N HEART OI?F.RMrION OURING PREGNANCY

tive repair during pregnancy of a diaphragmatic hernia even accidentally discovered. CARDlaC SURGERY...The reporled incidence of concomitant heart disease and,pregnancy is between 2 and 4% (141). Mo,'.st of these patients suffer from rheurnatic heart disease, predominantl?, mitral stenosis. Heart disease in a pregnant patient may cause high maternal mortality Three therapeutic approacb, es arc ,.~ .affable (1) therapeutic abortion, (2)non-operative management and (3) surg~t,al correction of the lesions• Col fronted with a pregnant patient who has slgmhcant heart disease, the cardiologist, obstetrician and cardiac surgeon should jointly cor~sider the problem. The decision as to which form of therapy is to be used must rest on results, and will depend, among other things, on the length of gest.,~.tion when the patient is seen. Althougt~ an early pregnancy may, of course, be aborted, the risk to the patient may be ,-¢. a,, great as allowing the pregnancy to gc~ ._ tc, term . H.owever, often t l '" ~e heart disease is ;rot recognized until the pregnancy has produced,s.,~",,nificant blood volume increase an~l cardiac failure. At this time, aborlJcn may be out of the question. Only appropriate evaluation after the failure is reversed will direct the therapy into a surgical or medical approac.:~. " -I In mitraI valve disease, the 25th to the 27th week are critical; patients in whom cardiac failure develops at this time may not respond to medical therapy and may require an urgent operation. Patients with refractory failure shouid be considered for operat.on. Congestive failure occurring after the 30th week, although uncommon, usuall.3, wil! respond to drug therapy. What type of procedure should be done? What are the results of cardiac surgery during pregnancy? Conger~ital cardiac lesions usually will require cardiopulmonary bypass; only pregnant patiems who are not responding to drug therapy for their heart lesion should be considered for surgical correction. For the most frequently encountered lesion, mitral stenos~s, the debate over open vs. closed correction continues and will not be settled here. Either type of operative procedure can be followed by a complicated course (see the following Case R@brt). Harken and Taylor (75), reviewing Mendelsohn's series of 385 cases, reported a maternal mortality of 1:8% and fetal toss of 9 ~,~ fohowmg closed micra1 commisst~rotomy. Some cases of mitraI stenosis will require the~:~',pen technic. Table 3 shows the re-ported instances of open heart prdeedures duringpregnancy and indicates an, improvement, in maternal and fetaI survival. Replacement of vah, es ca~ be done, and the greatest concern is the necessity for lop,g-term anticoagulation and its effect on the fetus. ,Again, the axiom seems to be to ignore the pregnancy and treat the cardiac disease as it would be treated in the non-pregnam woman. 45

CASE REPORT

(R. L. B., U K M C #01-57-27 l ) , a 34-year-old, obese female had had known rheumatic heart disease for 7 years. She was admitted with congestive heart failure 18 October 1963 when she was 4a/5. months pregnant. She was taking both digitalis and diuretics. In addition to her obesity, she showed dyspnea, rales at both lung bases, irregular pulse, grade 2 / 6 harsh diastolic murmurs at the apex, intrauterine pregnancy with fetal heart rate of t40/rain, and pitting edema at the ankles. Laboratory values were normal. Chest x-rav showed pulmonary congestion and left pleur'al effusign. The E C G demonstrated a tachycardia with numerous atrial ectopic beats. A closed mitral commissurotomy was performed after pretreatment with progesterone. On the first postoperative day her temperature rose to ~.01° F. On the third postoperative day an episode of' vaginal bleeding was treated with another dose of progesterone. That same day she developed atrial fibriliation with rates of 180/rain. Her pulmonary cor, gestion increased and her liver enlarged. By the next day she was in pulmonary edema and was hypotensive. She required fluid restriction, increased digitalis, frequent correction of a low serum potassium, antibiotics, diuretics and eventually phlebotomy. Because of continued hypotension on her fifth postoperative day, she was placed on vasopressor drugs. Despite all these measures, her pO~ gradually" decreased ~o 105 ram. Hg on !00%, O.~ by respirator through an endotracheat tube. With the hypoxia. she became semicomatose. An emergency tracheostomy greatly improved h e r condition. The tracheal secretions cultured out Proteus 'h~cn was sensitive to kanamycin. On administration of this appropriate antibiotic, her fever, which had gone a s high as 105 ° F., subsided and she was discharged 23 days after her operation. Throughout this complicated postoperative course, there is cn the chart no mention of the 'pregnancy. Only on the day of discharge was it noted that the fetal heart rate was i 4 0 / m i n . She was readmitted on two occasions with failure, and on 11 April 1964 she underwent a cesarean section because o f premature rupture of the membranes without ensuing :labor and delivered a 3,210-Gm., Apgar ! 0 m a l e infant.

SUMMARY T h e a p p r o a c h to a n y s u r ~ c a l condition occurring d u r i n g p r e g n a n c y should be t h e same as in the n o n - p r e g n a n t state. T h e systemic changes a n d gravid uterus m u s t not be allowed to o b s c u r e or confuse the diagnosis. S y m p t o m s that would be readi!y evaluated in a n o n - p r e g n a n t w o m a n m u s t be as eagerly investigated. O n c e the diag'nosis is established, e x c e p t d u r i n g late p r e g n a n c y , p r o m p t a p p r o p r i a t e surgical t h e r a p y should be u n d e r t a k e n . T h e r a p e u t i c abortion as an integral p a r t of the t r e a t m e n t of most surgicaI conditions during :pregnancy is falling into disrepute. T h e policy of interdicr.ing f u t u r e p r e g n a n c y 46

in p a t i e n t s veho h a v e h a d a m a l i g n a n c y is a l s o i n v a l i d . If sufficient t i m e h a s e l a p s e d f o l l o w i n g t r e a t m e n t to s u g g e s t t h a t t h e l i k e l i h o o d o f r e c u r r e n c e o r m e t a s t a s i s is s m a l l , p r e g n a n c y s h o u l d b e al.lowed.

REFERENCES i. 2.

3.

5. 6.

7.

8. 9. i0. 1 I. 12. I3. 14. 15, 16. 17 18.

Aaro, L. A.... lohnson. T, R., and Juergen. J. I.,.: Acute deep venous !hrombosis associated with pregnancy, Obst. & Gynec. 28:553, 1966. Aaro, L. A.. Johnson, T. R,, and Juergen. J. I_." Acute superficial venous thrombophlebitis associated v¢ith pregnancy, Am, J. Obst. & G ynec, 99:514, 1967. Abrams, F. R." Ci:'rhosis of the liver in pregnancy. Obst. & Gynec, 10:451. I957. Aguilion. A. Andjus, T.. Gravson. A.. and Race. ' - G. J Amniotic fluid embolism: A review. ObsL & Gynec. Surv, 17:6t9. 1962. Alders. N." A sign for ditTerentiating uterine from extrauterine complications of pregnancy, and the pue,"perium, Brit. M. J. "~ , ' 1.1t94," !c~51 ..... Allen, E. L., and Miller, E. C." Thyroid functk)n in normal pregnant>. pathologic pregnancy and in patients on orat contraceptives, North Caro.. lina M. J, 2,8:417, !967. Ass::di. N. S.. Rauramo, L., and Pettonen, T." Measurement of uterine hlood tiow and uterine rnetabolisnt. VIII. Uterine and fetal blood flow and oxygen consunlplion in early human pregnancy. Am. J,. Obs',. & Gynec 79:86, i 96O. Bacon. H. E., and Rowe, R. J." Abdominot2.erineat proctosigmoidectomy for rectal carcinoma complicating pregnancy. Report of four cases, South. M. J. 40"471. 19,+;.*" Baer, J. L., Reis. R. A.. and Arens, R. A.. Aplmndici~is in pregnancy wfth changes in position and areas of normal appendix in pregnancy. J.A.M.A. 98" 1359. 1932. Barber. H. R. K.. and t2runschwig, A." Gynecologic cancer complicating pregnancy. Am. J. Obst. & Gynec. 85" 156, i963. Barber, H. R. K., and Brunschwig. A.: Carcinoma of the ooze,." ' " Radiation and surgical management and pregnancy, Am. J. Obst. & t_~ 'nee. 100:926, t968. l~aumgartner, L., Wallace, H. M., Landsburg, E., and Pessin, V.- The inadequacy of routine reporting of fetal deaths, Am. J. PtJb. Health 39: t549, !949. Beller?~F. K . Thromboembolic disease :in pregnancy, Clin. Obst, & G . nec. I l"~'~0 t968. Betson, J. R., Jr., and Golden, M. D." Primary carcinoma of the ovary coexisting with pregnancy. Repot.*, of three cases, Obst. & Gynec. 12:589. 1958. Betson, J. R., Jr., and Golden, M. i).: Cancer and pregnancy, Am, J. Obst. & Gy;mc. 81:718, I96i. Bigtieri , Eo G., a n d Staton, D. E., Jr.: Pregnancy and primary atdosteron-, ism, J. CJin. EndocrinoI. 2 7 : t 6 2 8 , I967. Black, W. P.: Acute appendicitis in pregnancy, Brit; M. J. 1"1938, 1960, Boba, A., Plotz, E . J . , and L,inMe, D, M." Effects of atropine on fetal bradycardia and arteriM o x y g e n a t i o n : E x p e r i m e n t a l stlld3: in the dog during graded hemorrhage and following vasoprt.~sor administration. Surger> 58:267, i965. 47

19. Boba, A., Linkie, D. M., and Plotz, E. J." Effects of vasopressor administration and fluid replacement on fetal bradycardia and hypoxia induced by maternal hemorrhage, Obst. & Gynec. 27:,108, 1966. 20. Boronow, R. C." Extrape!vic malignancy and pregnancy, Obst. & G.vnec. Surv. 19:1, 1964. 21. Boucher, 13. J., :lnd Mason, A. S." Conn's syndrome, with associated ,.,',re,,-o nancy, Proc. Roy. Soc. Med. 58:575. 1965. 22. Bourgeois. G. A., and lqood, W. T.: Strangulated diaphragmalic hernia complicating pregnancy, New England J. Med. 241"150. 1949. 23. Breese, M. W." Cancer of the thyroid in wornen of childbearing age, Am. J. Ohst. & Gynec. 86: 616, 1963, 24. Br'lnschwig, A., and Barber, H. R. K." Cesarean section immediately followed by radic,iI hyslerectomv and pelvic node excision, Am. J. Obsi. & Gynec. 76" 199, 1958. 25. Bryan, W. M., Jr.: Surgical emergencies in pregnancy and in the puerperium, Anl. J. Obst. & Gynec. 70: 1204, 1955. 26. 13uchsbal.lm, H. J." Splenic rupture in pregnancy, Obst. & Gynec. Surv. 22" 381, 1967. 27. 13uchsbaunl, H. J." Accidental injury complicating pregnancy, Am. J. Obst. "). '3 & Gynec. 10_,75,., 1968. 28. Bunker, M. L., and Peters, M. V." Breast cancer associated with pregnancy or lactation, Am. J. ObsI. & Gynec. 85: 312, 1963, 29. Byrd, 13. F., Jr., Bayer, D. S., Robertson. J. C.. and Stephenson. S. E.. Jr.: "rreatment of breast tumors associated with pregnancy and lactation, Ann. Stir& 155"940, 1962". 30. Cannell, D. I_:., and Tovee, E. B." Post-partum obslruction of the large bowel, Postgrad. Meal. 21 "231, I957. 31,. Cantin, J., and McNeer, G. P." The effect of pregnancy on the clinical course of sarcoma of the soft somatic tissues, Surg., Gynec. & Obsl. 125" -), ..8, 1967. 32. Chapis, N.' Portacaval shunt performed during pregnancy, Am. J. Obst. & Gynec. 90:272, 1964. 33. Chikl, C. G., II1, and Douglas, P,. G.: St, rgicai problems arising during pregnancy, Am. J. Obst. & Gynec. 47:213, 1944. 34. Clarke, D. H." Peptic ulcer in women, Brit. M. J. 1"1254, I953. 35. Clever, J. E.: Radioactive iodine for hyperthyroidisn'~ administered during early pregnancy, Am. J. Obst. & Gynec. 61 '217, 1957. 36. Collins, !-t. A., Daniel, R. A., Jr., and Scott, H. W., Jr." Cardiac surgery during pregnancy, Ann. Thoracic Surg, 5"300, 1968. 37. Corm, J. W." Hypertension, the potassiuna ion and impaired carbohydrate tolerance, New England J. Med. 273" 1135, 1965. 38. Cooperman, L. H., Engelman, K., and Mann, P. E. G." Anesthetic management of pheochromocytoma employing halolhane and beta adrenergic blockade. A report of fourteen cases, Anesthesiology 28"575, 1967. 39. Cosgrove, S. A., and Brooks. R." Management .of surgical complications of pregnancy, Connecticut Med. 24:244, 1960. 40. Crane, M. C,,., Andes, J. P., Harris, J. K., and Slate, W. G.: Primary aldosteronism in pregnancy, Obst. & Gynec. 23 : 200, 1964. 41. Crooks, J., Aboui-Khair, S. A., Turnbull, A. C., and Hytten, F. E.: The incidence of goitre during pregnancy, Lancet 2:334, 1964. ,12. Danforth, D. N., Manalo-Estrella, I'., and Buckingham, J. C.: The efl'ects of pregnancy and of Enovid on the rabbit vasculattire, Am. J. Obst. & Gynec. 88'952, 1964. 43. Dills. P. V., Jr., Coopersmith, B., and Sweitzer, C.: Perforated peptic ulcer in pregnancy, Am. J. Obst. & Gynec. 99:293, 1967. 48

44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54.

55. 56. 57. 58. 59. 60. 61.

62. 63. 64. 65. 66.

Dilts, P. V.. Jr., Brinkman, C. R., III. Kirschbaum, T. H., and Assail, N. S.' Uterine and systemic hemodynanlic interrelationships and their response t o hypoxia, Am. J. Obst. & Gynec. 10.1" 138, 1969. Dimsdale, L. J." Valvular endocarditis with paradoxic emboli .I. Iowa M. Soc. 25 '448, 1935. Douglas, R. G." Surgical problems arising during pregnancy, Arn. J. Surg. 80: I, 1950. Dt:bourg, G., Broustet, P., Bricaud, H., Fontati, F., Trarieux, M., and Fontauille, P.: Correction complele d'une triade de Fallol en circuhiiion extra. corporelle, chez une femme enceinte, Arch. real. coeur 52: 1389, 1959. Dt, ncan, S. k. B.: Forearm venous tone in pregnancy, J. Physiol. 191"122 p. 1967. Dunn, J. M., and Raskind, R.: Ruplure of a cerebral arteriovenot, s malformation during pregnancy, Obst. & Gynec. 30:423, 1967. Dtinn, k. J., and Van Voorhis, L. W." Enigmatic fever and pelvic thrombophlebilis, New England J. Med. 276:265, 1967. Egdahl, R.. H., Kahn, P. C., and Melby, J. C.' Unilateral adrenaleciomy for aldosteronomas localized preoperaiively by differential adrenal vein catheterization, Surgery 64"117, 1'968. Elsas, L. J., Whittemore, R., and Burrow, G. N." Maternal and neonatal Graves' disease, J.A.M.A. 200"250, 1967. Embrey, M. P., GarreW W. J., and Pryer, D. L." Inhibitory action of halothane on contractility of human pregnant utert, s, Lancet 2" 1093, I958. Evans, G. k., Dalen, J. E., and Dexter, L.: Pulmonar.y embolisnl during pregnancy, J.A.M.A. 206:320, 1968. Fanfera, F. J., and Palmer, L. H " Pregnancy and varicose veins, Arch. Surg. 9 6 3 3 , 1968. Finn, W. F., and I.ord, J. W." Carcinoma of the colon producing acule inteslinal obstruction during pregnancy, Surg.. Gynec. & Obsl. 80:545, 1945. Fire, J. M., and Gould, P. k.: Thrombosis of the middle cerebral artery during pregnancy, Obst. & Gynec. 14:371, 1959. Fleischner, F. G." Recurrent pulmonary embolism and cot pulmonale. New England J. Med. 276" 1213. 1967. Flessa, H. C., Kapstrom, A. C., Glueck, H. i., and Will, J. J." Placental transport of heparin, Am. J. Obst. & Gynec. 93:570, t965. Fox, L. P., Grandi, J., Johnson, A. H., Watrous, W. G., arid Johnson, M. J." Pheochromocytoma associated with pregnancy, Am. J. Obst. & Gynec. 104" 288, 1969. Fred, H. L., Burdine, J. A., Jr., Gonzalez, D. A., Lockhart, R. W., Peabody, (2. A., and Alexander, J. K.: Arteriographic assessment of lung scanning in the diagnosis of pulmonary thronaboembolism. New England .I. Med. 275" 1025, 1"966. Friedman, E. W.: in Medical,.Surgical and Gynecologic Complications of Pregnancy, J. J. Rovinsky and A F. Guttmacher (eds.) (Baliimore: The Williams & Wilkins Company, 1962~). George, P. A., Fortner, J. G., and t<".ack, G. T." Melanoma with pregnancy. A report of i 15 cases, Cancer 13:854, 1960. Goodl'ich, S. M., and Wood, J. E." Peripheral venous distensibility and velocity of venous blood flow dtiring pregnancy or during oral contraceptive therapy, Am. J. Obst. & Gynec. 90:740. 1964. Gordon, R. D., Fishman, L. M., and Liddle, G. W." Plasma renin activity and aldosterone secretion in a pregnant woman with primary aldosieronism, J. Clin. Endocrinol. 27:385, 1967. Green, G. H." Pregnancy following cervical carcinoma in siiu. A review of 60 cases, .I. Obst. & Gynaec. Brit. Commonwealth 73"897, 1966. 49

67.

68. 69.

70. 71. ,,. 73. 74. 75. 76.

77.

Greene, R, R.. P e c k h a m , B. M., C h u n g , J. "r.. Bayly. M. A,. itcnar~m. It. B. \V., C a r r o w , L. A,, and G a r d n e r , G, H." Preinvasive carcinom;~ of the cervix during p r e g n a n c y , Surg,, (}.vnec. & ()bs!. 9 6 : 7 1 , 1953. Greene, R. R., and P e c k h a m , B. M." Pre;nva,~ive cancer of the cct~,x and p r e g n a n c s , A m . J. Obst. & Gynec. 7 5 : 5 5 1 . 195;~. G u s l a f s o n . G. W., G a r d i n e r , S. H., and Stoul. F. E." O v a r i a n tumur,~ c~mi. plicating pregnancy. A review of 45 surgically proved c,ses, Arll. J. f.~b,,l. & Gynec. 67: 1210. 1954. Haagensen. C. D.: C,mcer of the breast in p r e g n a n c y arm during lactati'.m. Am. J. Obst. & Gynec. 98: 141. 1967. H a e m m e r l i , U. P.: Ja,.,~dice l)t~rinl4 I"rc.k'luitlcy I N e w "Ym k Splio.gcr Verlag, 1967). i-lamiiIon, N. 7".. Paterson, I'. J . and Breid~hl, H ]). " l h y r o i d c c t c m y du~. ing pregnancy. M. J. Au~,tralia 1.,131. 19(~. Hamlin, E., Barlietl. M. K., and Smith, J. A • Ac'lle suxgical erectgentle'-. of the a b d o m e n in pregnancy. New En,gl..q~:d J..Med. _4 " 4. t 28.. 195 ". H a t e r , W. B.: Intestinal obstruction assocb~Icd ~ith prcgnanc.v. (.)~,,t. & Gxnec. !9:11. 1962. H a r k e n , D. E.. and "Fayler~ W. j • C a r d i a c surger,, d i n i n g j.~rcgrlar;c3. (.'!in. Obsl. & G y n e c . 4:697. 19bl. HarrJngton, S. W." C a r c i n o m a of the breast. Result.,, of ,,urgical ttg'atn~enl when lhe c a r c i n o m a occurred in the course of prcgnanc.~ t,r ],,oration anti ',,,hen p r e g n a n c y occurred subsequent to operation. I':~lO-1933. Ann. bt~rg. 106:690. t '937. tqarten.,,tcin, H.. and G a r d n e r , L. J " 'Fetany of the ncv, borl~ axsocialed with m a t e r n a l p a r a ; h v r o i d a d e n o ; n a New i.:.nv,)and J ,~lcd. 27.'1.,.~'~ ,, I ) 6 6 . Has'~elbach. K. A.. ~nd (.;ammellofl, ,'5. A • I)ie nculT;..lilat,,,~egui,~llon de, gr:tx'iden organi,.rnu~, i~iochem. Zschr. ~',8"206. ; 9 t 5. Halve. P." l"he m a n a g e m e n t of th.vromxicosis during p r e g n a n c y . B~it. J. ..%urg. 52:'7,31. 1965. Hayashi. T. T.. and Gilling. B," P!acental tran.,,fer of thi~>t:ra~.ii, f)b,,~. 8: Gynec. 30:736. 1967. Hehre, F. \ V . "ltmrapeulic d i l e m m a " R u p t u r e d inltacranial ::neurv,,rn in pregnancy. C o n n e c t i c u t Med. 2'9:859. i 965. H e n d e r s o n , M.. and Paterson. W. G . Perfor~.qion of }ciunurn by ret~cutun~ cell ::a~coma io. p r e g n a n c y . A m . J. Surg. I 15"3X5. ]96R. 14enne,,sy, J. P., :rod RollJno. A . ' H o d g k i n ' s disea.~e in pregnar, c : . ,,\ :¢p,.,rl of t _~ c~-scs. A m . J . Obs~. & Gvnec. . 6 3 : 7 5 6 . i'4~'~. .,_. b . . • . Hc~ .s., A I_.. and Selenkow. t*l A ('o:nt-.ined an~ithvr',',id-thvro~d t h e r a r,.w of h.vperthyroidism in pregmmcy. Ob.,,t. & Gvnec. " 1 ' 5-~ l.:ar,; Herbst. A. L., and Selenkow, H. A." H}~"~'rlhvroidism duzing p,rcgnar~cv N e w Engl~nd .I..Meal. .":'~~." . . . 6,.. " "z. 196s_ . H e r ~ h m a n . J. M.. and Starnes. "W. R . E x t r a c t i o n and char.'.,clerie'~:tior~ t~l" z, th.vrotropic maleriM iron~ the bun~an placenta.,, J. C'Iin. inve,,l, ax-~,"?. •

7g. 7% gO. 81. g2. ~3. ,,R"-~.

•

~

.

g5. ?,(~.

.

,-g

.

.

.

.

.

~l

('

¢

.

I u69.

g'r,. Hicke.v, R. C." Discus..,,ion f r o m s y m p o s i u m on cancer ol ,he b~easl. (Tuncer 20" !06f), 1'a67. 8g. Hil(tner. F . . I . . and O r m o n d , R. S.' Accuracx of 1he clinicai di;t,:nr~,,i~ r d p u l m o n a r y e m b o l i s m . , . A . M . A . 2 0 2 : 5 6 7 . 1967. ~. Hodgkinson, C. P.. and Krol]. J " lnguinul swelling during pregr:ancv...5,m. J. Obst. & Ci.vnec. 73:966. 1957. 0(!. t--l,:~ffmam. IS. S.. and Suzuki. M." Acute appendicitis in nregnvnc>'. :; ten .xeat survey. Am. J. Obst. & Gvnec. 67" 133~;, 195zi. 01. Hoileb, A. I.. and F:.,rrow. J. H.: ! b e re.~e.,ion of c~,rcinom;~ :ff ~hc brca,,: and p.regna'acy in 283 patients, Surg.. Gxnec, & ¢)bst. I t 5 6 5 , i962. 50

V2.

[~]uJlz+U",. I'.: T h e st.+p+n+ hypoten.~iun .~,lldrofIIc. 11~ inllX..,ft~+s~.ceto lh+ am:.;th,:ti~,t.Anc+lhe,,ia i ~"tpS 190(} I-lortoc~,,,, P.. und ]+co.nald. J. (~." "I }~.~.r~toxJc t::i.,,++aim II;~I~,'.~¢:IIm),,.~IIlc nia g~ a',.i.,in i)tegnanc'.,'. Po,~igJad. M . J. ,.12:,i(~. I9h~. tt~,.,,ie.~, J. S.. III. Airich. I:, ).I., and C+elg!lt~.,tl. i+. \¥." (;hl,~I~Itm,u ()I tl,, brci,~t in w'onlcn 35 }ca~:. ~)faye o~ )u~Jl|~el. ,'~nn. S,t,~,. )ht~.~~'~. l~/(,'.: .

94.

oa...

,

.

""

|

t

v5 2 i,-15. 1.95x | . t o ; v ~ d . B. K.. (juotlbor~, .I.l.)., umI :~e~tg~:r!. ~" %V i'." ',SUps:;,". il~,l)(~letl.',it)~ . ',~ n d ; ~ . ~ c in !ale l.)~egnanLy. ()bxI. & (,.~ n c c . I "37 I. I ~.5 .~. /It~ar.,i, I..A... I'em:. [. I, and I.enhe~I. A, !-." II)~t)r,il~t>j)/iI,.'|:i(~x~,i I~¢~ na~c t. A m . J. ()h~t. & (,Jyncc. 9T:t)II!. 1.9(,7. ()Is Jl,c~t,,. • , V,'. ~1., C o o J c } ' , I.)., a n d Ch,t.n. ( , . P.: ,..dltll,lt. ". " " N|IItL~I'V ~,','illIt';i.{llz,.;(~ porc;,I ,.:iicLliati~n dui Ing pl e.~g~;,v~c}'. ¢ )t)'~t. & C.}v~lcc. 25 " i ~q',;. 1')f,~' J a m , : - . t.. %. l hc etlec~, ol p a i n r c h ~ l l t , t a t , ) ~ a n d dcti~-t:ty u n liie lcl~:x ;~ n d ' ll,.:'ev t'~ ~j Ii. A;icxlJiesio]~12: . . . . ., I (){~. J e n ~ i n g , . . J. A.. aml ttt)(|gl,~llst,~ll. (. I'~. " A111it2Oalltlihll~ll I'o~ lltlllli~:Itar~, cmboli.,,m ~n p r e g m ~ n c y . ()b.',I. & (i.~ nec. 2.1:,x~. I t)t~,,l. l~!. IUllllCtl d t i r i n y pr~=gnanc.v, f o l l o w e d t,y argo,,! (>f :,a,h.e;~l i~e~(-rl~:,,u,~, a n d u~)e~,eili ltit deli~,cr.v, S ~ r g c : y (,3 : (,() I, ! 9(,S. l(t2 J o h f l s l o D , (i. "t,k'., (..iLl, doll, ,"~. (.J.. hIid R~2,/_,elx. H. '~¥.: i>ot-|;~cstv;~i ,d~l~tal I)elf()~ m e t | (.juJ i;)g ~ u ~ g e r } . . | . ( ) b s i . & (~y~)c~.'. " : 2 ?'-,'2. t ' ) / , ' ; Its3 Jonc,.. t ,:;., \ ; a l g , , , A.. l.elI, I. ( i , .".~'iJV~il)l'~. ('. I'..~late. \~,,'. (.,.. "VVa~g,l'... I. I . . ~:nd B t , / l o c k . 'W. K.' t'.ltici~:ncV (~f ~ l t t i p t e t,~lI~tII t;~lr~y 1,~ ~.,,~tc,:~ dc~.e;:l,,.,n d u ~ i n g IIlL'~{llill)~.'% ,/~ I)l',~y~~cy,', I~j|)t.)ll. (.}i1'-:I. ~( (.i>lIeC. 2;,"~:(). ]t)f'5 I().; Join:'-. t : (.,., , S c h w m n . ( . P.. Uuliuct<. W. K , V,~r/..':,. A.. 13u~In..I. I . . ] t i e d . n~ap.. H • . i , . , a n d W t : i r . J " to, ""~ nc~t " de~.cct.i(m, d u ~ i n g i)l~2~,:lt,lf!I2'v, . . r'~II. ~. ('}1.)~[. & (.i}r)cc. 11~1 "298. t968. 105 Joule'.. P. I-... Mcl-.van..'~,. B.. a n d }~,t:In~,rd. P.. M." li,,t.~n(.,rlhafe a n d p c r t:~ra,~iu:~ coml)l~cat;IW i)Cl)iic: t1](.ci ~ f~lcL,,l~allc?,. IA~nc,.'! I ' 3";(}. l'¢Gb'. i~apJ,~}, N.. l . ) i M a r c , S.. a n d i.)t'l~I,l~,t.)f;, ( , " 'l h(omt:ophlei:)i~.i.,, ~ t Ii:¢ ov'-~. ri;.~v) vclr!. :\:}1. J. (.)b51. t~;:(..iynL'C. I II:~ "V35, I'~1'~'} I(17. l'(~.~ r h. ~nd Slllilll, N.' ,). (gCI~ ill ltte. f)rci:F~iitll Cu!di>,c Imtien!, A~:~..I C;d(.ii(.:'} ~""~(~'~ i;)¢;'; ! (.)~. KeJ.',.<:. 1. ~A.. an(I i : u n n e i ] . J. W (_~r~,~:om;, o f tl),: c c r v , x c(u~)plic~,linv p~¢gm~nc'...I O k J a ! ~ o m a .%1 ,\ (~1.~:51}~ ,t,, ~, . tJit:,,=l will, ~n;.~'s~,c I(~,. Kit]~.:. C. (i.. Slerdn~an.. I'C,.,a n d l:Itn;-,..I. f!. ". l)uod,'n:~l h c ~ n o r r h u t , c c:ui11/')licalirig I'uegn;~nc). C a l i l u ~ m a M e d . II)(~'40i, ]Vf,':" ~, ;(} KiSlHCI'. R ~',V (.iOl"I.~i.tCIi. ,'X (. itnd ,N,I;iI}~, (..,. \ ' ( ~ct vic;,i ~'aVi(l~," ill j~l~.~,,.. ;)a~IC','. (.)i3sI. & ()}1?t:C. t~.55A. 195"" Iii. K ~ z a m . t?,. [... C o n k l i n . I'. I"., C i i ~ n n e l l i . S.. I;....~t'tcV. P., a n d ( . h ~ . I ) . O l ~ e n - h c a r l sutlecrv foz ~nitr;ii .,,t~t~u.,,i,. du!in.u i)re,g.'n,~ncy, J. | h u r a c i c t~ (;ardiova-:.. Surg. 53"5.x7. t9f,'7. Kricge.r.H.P." in A~ed~ca/. ~.,;,-~.-:~ca: am/" (.;.~'i(.ru,,~,~; ('_,-/~p,~,a/~,-~(.~ ,.,t f-':'eA,n a m ~. J. J. Rovir),&y a n d A. F. (..~tlti~:li~cl~er f t:',is..~ (BaJli~Ii(>rc: I h , : vvirlit, mx 6: W i l k i n x ('_()ml)arsy. 19(,5 ) I13 Kri~,,.e/~zaard, N.. a n d Mt.,y:~. i . " InvcM~gali~m,. o f p / a c e ~ l a I Ihte.~i~oJd.~ I(.~ s~ccin3'lci~oline..hnt:'~the:,~ol,,gy 22"'7 19r~7. ] I,I. l . ; , c k n e r , f. l-' . a n d I u'.,.,,k). /\. t~.- Ai)t~rlion a~ ;, comp/ica~.ion of ,.,p~:ralion in Ihe p r e y n a n ~ v, u m n n . A m . J. S u r g . 4(,:3~;2. ! 9 3 2 . I.anc. !:. \V.. Jr., a n d N e v i c i l e . I). W.. l r . ' l:acl,.~r.s ;,iieciinL.' It~c l)rogr~o-~i~ I !5 in the lre'~l,m:n', o f ,:arcirlom~.; o f lhc u l c r i n c ccrvi.x. I t . N,~vv t.(n.u..land ()b:~I. & C;vnec. Soc. ;~" l ? , 1965. •

"

•

51

•

f

¢

•

I "

116. Langmade, C. F.: Epigastric pain in pregnancy toxemia. A report of fatal peptic ulcers in toxemia, West. J. Surg. 64:540, 195(}. I17. Langmade, C. F., and Edmondson, M. A . Acute pancreatitis during pregnancy and postpartum period, Surg,, Gynec. & Obst. 92:43, 1951. 118. Lee, W. H., Jr., and Pate, J. W." Surgical aspects of heart disease in pregnancy, GP 28"78, 1963. I19. l_e Winn, E. B.: Peptic ulcer with hemorrhage during pregnnncy and fetal death, Am..1". Obst. & Gynec. 54"t 14. 1947. 120. I..eyes, R., Ofstun, M Dillard, D. H., and Merendino, K. A.: Congenital aortic stenosis in pregnancy, corrected by ext~acorpc~e,~l circulation, J.A.M.A. 176: 10(}9, 1961. 121. Lloyd, T. S., Jr.' The safety of surgical operations during pregn~ncy, South. NI. J. 58' 179,-1965. 122, Lotze, E. C., Kaufman, R. H., and Kaplan, A. L..: Postpartum ovarian vein thrombopblebitis, Obst. & Gvnec. Surv. 21 85.., 1966. l_udwig, G. D." Hyperparathyroidism in relation to pregnancy, New England J. Med. 267"637, 1962. 12.4. Lynch, J. K., Sreenivas, V., and Pelliccia, O." Ovarian-vein thrombophlebilis, New England J. Med. 275 : 112, 1966. 125. MacFar!ane, J. R., and Tho~'bjarnarson. B . Ruptt~re of splenic artcry aneurysm during pregnancy, Am. J. Obst. & Gynec. 95"!025, 1966. 126. MacMahon, B," Prenatal x-ray exposure and childhood cancer, J. Nat. Cancer Inst. 28: 1173, 1962. 127. Man, E. B., Reid, W. A., and Jones, W. S." Thyroid function in human pregn~ncy. [. The significance of serum butanol-extractable iodines in the last: trimester, Am. J. Obst. & Gynec. 90:474, i964. 128. Man, E. B., Reid, W. A., Hellegers, A. E., and Jones. W. S." Thyroid function in human pregnancy. II. Serum butanol-e×tractable iodine values of pregnant women 14 through 44 years, Am. J. Obst. dr Gynec. 103"3z8, 1969. 129. Ma1~, E. B., Reid, W. A., and Jones, W. S.: T17.yroid function ir~ human pregnancy. 1II. Serum thyroxine-binding prealbumin (TBPA) and thyroxine-binding globulin (TBG) of pregnant women 'age 14 through 43 ye~lrs. Am. J. Obst. & Gynec. 103:338, 1969. 130. Man, E. B., Reid, W. A . , and Jones, W. S." Thyroid function in human pregnancy. IV. Serum butanol-extractable iodine drop with weight gain, Am. J. Obst. & Gynec. 102: 244, 1968. 131. Manalo-Estrella, P,, and Barker, A. E.: Histopathologic findings in ht, man aortic media associated with pregnancy" A study of 16 cases, Arch. Path. 83:336, 1967. 132. Mannix, E. P., Jr., and Mahajan, D. R." Open heart surgery during pregnancy, J. Thoracic & Cardiovas. Surg. 53" 592, 1967. 133. Marcus, M. B., Cibley, L. J., and Brandt, M. L." A case of carcinoma of the rectum complicating pregnancy and a review of the literature, Am. J. Obst. & Gynec. 73: 1337, 1957. 134. Marsh, M., and Fitzgerald, P. J." Carcinoma in situ of the human uterine cervix in pregnancy, Cancer 9:1195, 1956. 135. McCausland, A. M . , Hyman, C., Winsor, T., and Trotter, A. D., Jr.: Venous distensibility during pregnancy, Am. J. Obst. & Gynec. 81"472, r

1961.

136. McCorriston, C. C.. Non-obstetrical abdominal st, rgery during pregnancy, Am. J. Obst. & Gynec. 86:693, 1963. I37. McDonald, A. L.: Appendicitis in pregnancy, Am. J. Obst. 18: I I 0, 1929. 138. McGowan. L.: Cancer and pregnancy, Obst. & Gynec. Surv. 19:285, 1964. 5"2

139. McGowan, L.: Cancer in Pregnancy (Springfield, 111.: Charles C Thomas, Publisher, 1967). 140. McLean, 13. W., Arminski, T. C., and Bradley, G. T.: Management of primary carcinoma of the rectum diagnosed during pregnancy,,Am. J. Surg. 90:816, 1955. 141. Meffert, W. G., and Stansel, H. C., Jr.: Open heart surgery during pregnancy, Am. J. Obst. & Gynec. 102:I116, 1968. 142. Meiling, R. L.: Appendicitis complicating pregnancy, labor, and the puerperium, Surg., Gynec. & Obst. 85:512, 1947. 143. Merkatz, I., Martin, K. A., and Beal, .I.M.: Gastric secretion during pregnancy and lactation, Obst. & Gynec. 24:587. 1964. 144. ,Mestman, J. H., Niswonger, J. W. H., Anderson, G. V., and Manning, P. R.: Ewduation of thyroid function ,:luring and after pregnancy, Am. J. Obst. & Gynec. 103:322, I969. 145. Mikuta, J. J., Enterline. H. T., and Braun, T. E., Jr.: Carcinoma in situ of the cervix associated with pregnancy. A clinical-pathological review, J.A:M..A. 204:763, 1968. 146. Mikuta, J. J.: lnvasive car.,:inoma of the cervix in pregnancy, South. M. J. 60:843, !967. 147. Millen, J. W . Irradiation and congenital malformation, Practitioner 191" 143, 1963. 148. Miller, J. R., Stoelting, V. K., Stander, R. W., and Warring, W,: In vitro and in vivo responses of the uterus to halothane anesthesia, Anesth. & Anal& (Cleveland 45:533. 1966. 149. Montgomery, J. B.: The effects of halothane on the newborn infant delivered by caesarian section, Brit. J. Anaesth. 33:156, 1961. 150. Moore, J. G., O't.eary, J. A., and Johnson, P. M.: The changing impact of pulmonary thromboembolism in obstetrics, Am. J. Obst. & Gynec. 97:507, 1967. 151. Moya, F., and Thorndike, V.: ~issage of drugs across the placenta, Am. J. Obst. &: Gynec. 84:1178 (part 2), 1962. 152. Moya, F., and Spicer, A. R.: An Appraisal of Halothane in Obstetrics. Chap. 8 in Clinical Anesthesia, N. M. Greene (ed.) (Philadelphia: F. A. Davis Company), pp. 173-180, 1/1968. 153. Nabatoff, R. A.: Varicose veins of pregnancy-, J.A.M.A. 174: 1712, 1969. 154. Nabatoff, R. A.: in Medical, Surgical and Gynecologic Complications o] Pregnancy, J. J. Rovir, sky and A. F. Guttmacher (eds.) (Baltimore: The Williams & Wilkins Company, 1965). 155. Nash, A. G.: Perforated large bowel carcinoma in late pregnancy, Proc. Roy. Soc. Med. 60:504, 1967. 156. Oberst, F. W., and Plass, E. D.: The acid-base balance in the plasma and blot~d cells of normal nonpregnant, pregnant and puerperal women, J. Lab. & Clin. Med. 26:513, 1940. 157. O'Leary, J. A., and Bepko, F. J., Jr.: Portacaval shunt performed during pregnancy, Obst. & Gynec. 20:~43, 1962. O'Leary, J. A., and Bepko, 'F. '~1., Jr.: Rectal carcinoma and pregnancy, 158. Am. J. Obst. & Gynec. 84:459, I962. O 159. ' ¢ 't.ear),r J. A., Pratt, J. H., and Symmonds, R. E.: Rectal carcinoma and pregnancy: A review of 17 cases, Obst. & Gynec. 30:862, 1967. 160. Olley, P. M., and Whitaker, W. L.: Postpartum pulmonary hypertension. Obst. & Gynec. 29:369, 1967. 161. Pack, G. T., and Scharnagel, I. M. : The prognosis for malignant melanoma in the pregnant woman, Cancer 4:324, 1951. 162. Peckham, B., Greene, R. R., Chung, J. T., Bayly, M. A., and Benaron, 53

163. 164. 165. 166. 167. 168. 169. 170. 171-. 172. 173. 174. 175.

1:/6. 177. 178. I79. 180. I81. 182. 183. 184. 185.

186.

187.

H. B. W.: The relation of pregnancy to abnormalities of the cervical epithelium, Surg., Gynec. & Obst. 99:40l, 1954. Peckham, C. H., and King, R. W.: A study of intercurrent conditions observed during pregnancy, Am. J. Obst. & Gynec. 87:609, 1963. Penman, W. R.: Hiatus hernia. A cause of persistent gastrointestinal disturbances in pregnancy, West. J. Surg. 59:622, 1951. Petri, K. E.: An evaluation of the medical management of thyrotoxicosis in pregnancy, J. Arkansas M. Soc. 62:230, 1965. Pool, J. L.: Treatment of intracranial aneurysms during pregnancy, J.A.M.A. 192: 209, 1965. Prem, K. A., Makowski, E. L., and McKeevey. J. L.: Carcinoma of the cervix associated with pregnancy, Am. J. Obst. & Gynec. 92:99, I966. Prout, T. E.: Thyroid disease in pregnancy, Am. J. Obst. & Gynec. 96: 148, 1966, Prowse C. M., and Gaensler, E. A.: Respiratory" and acid-base changes during pregnancy, Anesthesiology 26:381, 1965. Pruitt, A. B., and Mole, H. W.: Middle cerebral artery occlusion in pregnancy, Obst. & Gynec..29:545, 1967. Quattlebaurn, F. W., and Hodgson, J. E.: Vein stripping in pregnancy, Minnesota Med. 49:245, 1966. Quilligan. E. J., and Tyler, C.: Postural effects on the cardiov~ascular stattzs in pregnancy. A comparison of the lateral and supine postures, Am. 3. Obst. & Gynec. 78:465, I959. Radman, H. M.: Pregnancy complicated by nonobstetric surgical disease, Arch. Surg. 88:279, 1964. Rand, C. W., and Andler, M.: Tumors of the brain complicating pregnancy, Arch. Neurol. & Psychiat. 63:1, 1950. Randall, L. M.: Carcinoma of the breast and pregnancy, Am. J. Obst. & Gynec. '78:1353, 1959. Reed, T. P., Wasylenki, M., Brod, R. C., and Marchant, D.: Vena caval plication during pregnancy, Obst. & Gynec. 29:838, 1967. Riva, H. L., Anderson, P. S., and O'Grady, J. W.: Pregnancy and Hodgkin's disease, Am. J. Obst. & Gynec. 66:866, 1953. Roddick, J. W., Jr., and Crossen, P. S.: Invasive cervical carcinoma during pregnancy, Am. J. M. Sc. 25I :736, 1966. Romney, S. L., Gabel, P. V., and Takeda. Y.: Experimental hemorrhage in late pregnancy, Am. J. Obst. & Gynec. 87:636, 1963. Rubin, A., Chaykin, L., and Ludwig, G. D.: Maternal hyperparathyroidism and pregnancy, J.A.M.A. 206: 128, 1968. Rubin, H. W.: Ligation af the inferior vena cava in early pregnancy, Am. J. Obst. & Gynec. 80:542, 1960. Russell, K. P., Rose. H., and Star:r, P.: The elTect of radioactive iodine on maternal and fetal thyroid function during pregnancy, Surg., Gynec. & Obst. 104:560, 1957. Sabbagha, R. E., and Hayashi, T. T.: Transfer of C14-thiouracil during pregnancy, Am. J. Obst. & Gynec. 103:t2I, 1969. Saidi, P., H o a g , M. S., and Aggeler, P. M.: Transplacental transfer of bishydroxycoumarin in the human, J.A.M.A. 191:761, 1965. Sandweiss, D. J., Podolsky, H. M., Saltzstein, H. C., and Farbman, A. A.: Deaths from perforation and hemorrhage of gastroduodenal ulcer during pregnancy and the puerperium, Am..1. Obst: & Gynec. 45:131, 1943. Sauer, H. A.: Paradoxical embolism in pregnancy, J. Obst. & Gynaec. Brit ~. Emp. 62:902, 1955. Schuller, T.; Cojolaru, I., Lorincz, 1., Olariu, S., and Schapira, T.: Primary 54

188 189. 190, 191. 192. t93. 194. 195. 196. 197. 198. i99. 200. 201. 202. 203. 204. 205. 206. 207. 208, 209. 210. 211. 212. 213. 214. 215.

malignant lymphogranulomatosis of the stomach associated with pregnancy, Oncologia (Basel) 20:291, 1966. Scott, R. C., and McElin, T. W.: Argentaffinoma of the appendix in pregnancy: A report of a case, Illinois M. J. 133: 181, 1968. Scudamore, J. H., and Molt. J. C.: Rtlpture of an intracranial aneurysm during pregnancy, J. O,bst. & Gynaec. Brit. Commonwealth 73: 1019. 1966. Shires. T., Cola. D., Carrico, V., and Lightfoot, S.: Fluid therapy in hemorrhagic shock, Arch. Surg. 88:688, 1964. Shocker, E. C., and Fortner, J. G.: Melanoma and pregnancy. An experimental evaluation of a clinical impression, S. Forum 9:671, 1958. Smith, J. A., and Bartlett, M. K.: Acute surgical emergencies of the abdomen in pregnancy, N e w England J. Med. 223:529, 1940. Sparkman, R. S.: Gallstones in young women~Ann. Surg. 145:813, 1957. Speert, H., Graft, S., and Graft. A. M.: Serum phosph~ltase relations in molher and fetus, Am. J. Obst. & Gynec. 59: 148, 1950. Stander, R. W., and Lein, J. N.: Carcinoma of the cervix find pregnancy, Am. J. Obst. & Gynec. 79:164, 196(}. Sterling. T. D., Saenger, E. E., and Phair, J. J.: Radiation epidemiology, Cancer i5:489, 1962. Stewart, A., Webb, J.. and Hewitt, D.: A survey of childhood malignancies, Brit. M. J. l :495. 1958. Stewart, A.: Etiology of childhood malignancies. Brit. M. J. 1:452, I96I. Stone, S. R., Whalley, P. J.. and Pritchard, J. A.: Inferior vena cava and ov~lrian vein Iigation during late pregnancy, Obst. & Gynec. 32:267, 1968. Strange, S. L." Massive hemorrhage from duodenal ulcer in pregnancy, Proc. Roy. Soc. Med. 55:798, I962. Strauss, M. B., and Castle, W. B.: Gastric secretion in pregnancy and the puerperitm'J, Am. J. M. Sc. ! 84:655, 1932. Swenson. A. O., and Runquist, J. M.: Spontaneous rupture of the splenic artery, Minnesota Med. 49: 1701, 1966. Tarnoff, J.. Less, W. M., and Fox, R. T.: Major thoracic surgery during pregnancy, Am. Rev. Resp. Dis. 96:i 169, 1967. Thomford, N. R., Patti, R. W., and Teteris, N. J.: Appendectomy during pregnancy, Surg., Gynec. & Obst. 129: 489, ! 969. Treves, N., and Holleb, A. L.: A report of 549 cases of breast cancer in women 35 years of age or younger, Surg., Gynec. & Obst. 107:271, 1958, Ullery, J. C.: Thromboembolic diseases complicating pregnancy and the ptlerperium, Am. J. Obst. & Gynec. 68: I243, 1954. Varner, J. B.: In disct~ssion of paper by Bryan, W. M., Jr. ( # 2 5 ) . Villa Santa, U.: Thromboembolic disease in pregnancy, Am. J. Obst. & Gynec. 93:142, 1965. Vincent, C. R.: Jaundice in pregnancy. A review from the Charity Hospital, New Orleans, 1941-1956, Obst. & Gynec. 9:595, 1957. Wagner, G., Transbol, I., and Melchior, J. C.: Hyperparathyroidism and pregnancy, Acta endocrino~. 47:549, 1964. Waldrop, G.. M., and P Nr~er; J. P.: Carcinoma of th~ cervix associated with pregnancy, Am. J. Obst~i,,& Gynec. 86:202, t963. Walker, R. M.: Pheochromocytoma in relation to pregriancy. Brit. J. Surg. 51:590, 1964. Warfield~ C, I,: Acute appendicitis complicating pregnancy. Po~tgiaa. Med. 8:10, 1950, Warren, R. P." Carcinoma of the rectum and pregnancy, Brit. M. J. 45:61, 1957. Wells, J., and Steer, C. M.: Relationship of leukemia in children to abdom55

216. 217. 218.

219. 220. 221. 222. 223.

inal irradiation of mother during pregnancy, Am. J. Obst. & Gynec. 81: 1059, 1961. Werner. S. C.: Panel discussion on hyperthyroidism. 1. Hyperlhyroidism in the pregnant woman and the neonate, J. Clin. Endocrinol. 27: 1637, 1967. Whailey, I'.: Hyperparathyroidism and pregnancy, Am. J. Obsl. & Gynec. 86:517, 1963. While, L. P., l.inden, G., Breslow, L., a:,d H;irzfeh.1, L.: Studies on melanoma. The effect of pregnancy on survival in human melanonla, J . A . M . A . 177:235, 1961. White, T. T.: Prognosis of breast cancer foF pregnanl and nursing women. Analysis of 1,413 cases, Surg., Gynec, & Ob:~t. 100:661, 1955. White, T. T., and White, W. C.: BFeast cancer and pregnancy. RcpoFt of 49 cases follm,ved 5 years, Ann. SuFg. 144 : 384, 1956. Williams, T. J., and "Turnbvll, K, ['.: Carcinoma in situ and pregnancy, Obsl. & Gynec. 24:857, 1964. Wylie, I. G.: Spontancot,s rupture of the splenic artery in early pregnancy, Postgrad. M. J. 43:662, 1966. Zuhdi, N., Carey, J., Schmidt, A., and Greer, A. : Total body perfusion and pregnancy, J. Internat. Coll. Surgeons 43:43, 1965.

56