699 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 49 Fetal Surgery Procedures and Associated Maternal Complications Robert H. Ball 1 & Michael A. Belfort 2 1 HCA Fetal Therapy Initiative, St Mark ’ s Hospital, Salt Lake City and Division of Perinatal Medicine and Genetics, Departments of Obstetrics, Gynecology and Reproductive Sciences, UCSF Fetal Treatment Center, University of California, San Francisco, CA, USA 2 Department of Obstetrics and Gynecology, Division of Maternal - Fetal Medicine, University of Utah, Salt Lake City, UT and HCA Healthcare, Nashville, TN, USA Introduction A discussion of the potential maternal complications of fetal surgery is pertinent given the fact that such complications are in theory absolutely avoidable. As the term suggests, fetal surgery is performed for the sole physical benefi t of the fetus, and any risk to which the mother is exposed is for a purely altruistic purpose. There is no direct health benefi t to the mother. Many of the fi rst fetal surgical procedures depended on mater- nal laparotomy to expose the uterus and hysterotomy to expose the fetus. This approach then evolved into laparotomy with uterine endoscopy rather than hysterotomy to preserve the integ- rity of the uterus. With further experience laparotomy has been for the most part been replaced with percutaneous procedures using telescopic devices with a diameter of 3 mm or less. The progression to microinvasive fetoscopic approaches has reduced the potential for morbidity, but not eliminated it [1] (Table 49.1 .). Each one of these approaches and associated complica- tions will be discussed in more detail below. Hysterotomy Hysterotomy, while less frequently used now, is still employed in some cases where endoscopic techniques are not possible. These include repair of neural tube defects, and the removal of sacro- coccygeal teratomas and other masses. Hysterotomy - based pro- cedures are usually dependent on intraoperative ultrasound guidance (both before and after abdominal wall incision). Once the patient has had anesthesia (general endotracteal) and the sterile fi eld has been established, ultrasound is used to determine the fetal lie. If the lie is unsuitable for the proposed surgery, external version and transabdominal manipulation is employed under ultrasound guidance to position the fetus such that the fetal surgical site is near the fundus. Depending on the maternal body habitus and fetal size and position this may be quite chal- lenging. Laparotomy is then performed and the ultrasound trans- ducer, covered in a sterile sleeve, is placed directly on the surface of the uterus. The placental edge is identifi ed, a critical step in making the decision on where to perform the uterine entry. Ideally the uterine incision is best centered as far from the pla- cental edge as possible because once amniotic fl uid escapes the uterus defl ates. Despite taking this precaution the uterine incision will almost always still be in relatively close proximity to the placental edge – which increases the risk of bleeding and abrup- tion. If signifi cant bleeding cannot be readily controlled immedi- ate delivery will be required for maternal safety. Generally the incision in the uterus will have been made such as to have optimal access to the fetal part to be surgically addressed. Ultrasound is used for transuterine monitoring of the fetal heart during the procedure. Following completion of the fetal intervention, the membranes and myometrium are closed with several layers of suture. A cath- eter is left in the uterine cavity to allow lactated Ringer ’ s solution to be infused together with antibiotics. Ultrasound is used to determine the volume of “ amniotic ” fl uid, which generally is left at a low normal level to minimize stress on the suture line. Postoperative management usually involves tocolytic therapy of some sort. The regimen in San Francisco included 24 hours of intravenous magnesium sulfate and oral indomethacin for a total of 48 hours. Long - term tocolytic maintenance with nifedipine is then substituted and continued until delivery. Prophylactic anti- biotics are continued for 24 hours. Ultrasound monitoring is used daily to evaluate fetal health (biophysical profi le and ductus arteriosus patency), amniotic fl uid volume, and cervical length. Hospital discharge generally occurs 4 – 5 days after surgery. If all goes well long - term monitoring with ultrasound continues at a weekly frequency. Chapter 49 700 labor, premature rupture of the membranes, and preterm deliv- ery. Infectious complications are rare, except when premature rupture of the membranes leads to prolonged latency. An impor- tant additional discussion point is that all subsequent deliveries, including the index pregnancy, must be by cesarean section. Data regarding future fertility are reassuring, with no increased inci- dence of infertility in the UCSF experience in those patients attempting pregnancy [6] . Experience from the Children ’ s Hospital of Phildelphia (CHOP) suggests a concerning risk for uterine rupture/dehiscence in subsequent pregnancies that may be as high as 6 – 12% [7] , which would be considerably higher than the risk after previous low transverse cesarean section (1% or less) [8] or classical cesarean section (5 – 10%) [9] . Another theoretical risk in subsequent pregnancies is placenta accreta. This is because the hysterotomy performed in the second trimester is never in the transverse lower uterine segment and therefore the patient is exposed to two uterine incisions during the pregnancy. The risk of accreta increases when implantation is in an area of uterine scarring and multiple incisions will increase the likelihood of implantation in such an area. To our knowledge there has not been a single case of placenta accreta in a fetal surgical patient from UCSF in a subsequent pregnancy. Fetoscopy The growing popularity of videoendoscopic surgery in the 1990s, combined with the earlier experience with fetoscopy, paved the way for endoscopic fetal surgery. The belief was that a smaller disruption of the amniotic membranes would ameliorate some of the limiting steps in fetal surgery, viz. (i) preterm labor, which was believed to be triggered by the large uterine incision required We have recently reviewed our experience at UCSF with mater- nal hysterotomy [1] (Table 49.1 ). Eighty - seven hysterotomies were performed between 1989 and 2003. There were signifi cant immediate postoperative complications. In the early experience, pulmonary edema was common and is believed to be related to the use of multiple tocolytic agents (particularly nitroglycerin and beta stimulants) combined with steroid use and aggressive fl uid management [2] . Thirteen per cent of women having a hyster- otomy required transfusion for intraoperative blood loss. Fifty two per cent of these patients suffered postoperative preterm premature rupture of the membranes (PPROM) and 33% devel- oped preterm contractions refractory to maximal therapy and delivered preterm. The mean time from hysterotomy to delivery was 4.9 weeks (range 0 – 16 weeks). The mean gestational age at the time of delivery was 30.1 weeks (range 21.6 – 36.7 weeks). Others [3,4] have had similar experience with preterm delivery following hysterotomy. With experience much of the morbidity associated with hysterotomy has decreased and clinically signifi - cant pulmonary edema and blood loss are now less common. The mean gestational age at the time of delivery following repair of meningomyelocele (MMC) is now approximately 34 weeks [5] . Discussion of the risks, benefi ts and alternatives of the proce- dure are important, and must include a clear disclosure of the experimental nature of the surgery. The risks to the mother are similar to those seen in any major abdominal surgery, although in this case as mentioned above, there is no direct physical benefi t to her. She should understand the risks associated with aggressive tocolytic therapy and those resulting from bed rest in a hyperco- agulable state (venous thromboembolism). The risks to the fetus are primarily the result of intraoperative vascular instability and hypoperfusion (leading to injury or death) and the pathology of preterm delivery. The risks to the pregnancy are primarily preterm Table 49.1 Maternal morbidity and mortality for 178 interventions at UCSF with postoperative continuing pregnancy and divided into operative subgroups. Operative technique Open hysterotomy Endoscopy FETENDO/Lap - FETENDO Percutaneous FIGS/Lap - FIGS All interventions Patients with postoperative continuing pregnancy 79 68 31 178 Gestational age at surgery [wks] 25.1 24.5 21.1 24.2 Range [wks] 17.6 – 30.4 17.9 – 32.1 17.0 – 26.6 17.0 – 32.1 Gestational age at delivery [wks] 30.1 30.4 32.7 30.7 Range [wks] 21.6 – 36.7 19.6 – 39.3 21.7 – 40.4 19.6 – 40.4 Interval surgery to delivery [wks] 4.9 6.0 11.6 6.5 Range [wks] 0 – 16 0 – 19 0.3 – 21.4 0 – 21.4 Pulmonary edema 22/79 (27.8%) 17/68 (25.0%) 0/31 (0.0%) 39/178 (21.9%) Bleeding requiring blood transfusion 11/87 (12.6%) 2/69 (2.9%) 0/31 (0.0%) 13/187 (7.0%) PTL leading to delivery 26/79 (32.9%) 18/68 (26.5%) 4/31 (12.9%) 48/178 (27.0%) Preterm premature rupture of membranes (PPROM) 41/79 (51.9%) 30/68 (44.1%) 8/31 (25.8%) 79/178 (44.4%) Chorioamnionitis 7/79 (8.9%) 1/68 (1.5%) 0/31 (0.0%) 8/178 (4.5%) FETENDO, fetal endoscopic procedure; Lap - FETENDO, laparotomy and fetal endoscopic procedure; FIGS, fetal image - guided surgery; Lap - FIGS, laparotomy and fetal image - guided surgery. Fetal Surgery Procedures and Associated Maternal Complications 701 cavity. It may also improve placental perfusion and makes the patient more comfortable. In many cases little or no tocolytic medication is needed and patients are generally discharged within 24 hours or less of the procedure. The risks of fetoscopy are related to uterine puncture as well as to the specifi c procedure that is being treated. In some cases adverse outcomes may be inherent in the disease state itself such as mirror syndrome (Ballantyne syndrome) in TTTS [11] . Preoperative measurement of the cervix can be used to assess the risk for premature delivery after fetoscopy [12] . When the cervix is less than 30 mm the data suggest a 74% risk for delivery prior to 34 weeks. If the cervix is shorter than 20 mm the vast majority of patients miscarry. After fetoscopy the risk for preterm premature rupture of membranes (PPROM) is estimated to be approximately 10 % or less and the risk for abruption is 1 – 2%. The rate of abruption is believed to be related more to the amnio- reduction than the use of the fetscope. Less common complica- tions are chorioamnionitis and hemorrhage. Shunts and r adiofrequency a blation Shunts are used for chronic drainage of fl uid - fi lled fetal cavities, organs and cysts. The fi rst shunt was developed by Harrison at UCSF in the early 1980s [13] . This was essentially a double pigtail shunt introduced through a 14G introducer (Cook Medical, USA). The Rodeck shunt, developed during the same time period in the UK, is also a double pigtail shunt, but is longer and has a greater diameter (Rocket Medical, UK) than the Harrison shunt, and it uses a larger diameter introducer [14] . These shunts are placed in fetuses with an obstructed bladder, pleural effusion(s) and large type I congenital cystic adenomatoid malformations (CCAMs). With most shunt procedures, a small incision is made in the maternal skin, and the introducer with the trochar in place is advanced into the amniotic cavity. Care is taken to evaluate the myometrium that will be traversed with a high - frequency trans- ducer (to improve the resolution of the tissue) and with color fl ow Doppler with low fl ow settings, to avoid damaging large veins. We generally avoid a transplacental approach but if no other approach is available shunts can be placed transplacentally. The trochar and introducer are then advanced into the area to be drained. Once in position the trochar is removed and care is taken to not allow sudden decompression of the fl uid - fi lled cavity by placing a fi nger over the end of the introducer. The shunt is then loaded into the introducer and advanced using a pusher until the internal coils exit the introducer. It is critical to continuously image this process with ultrasound. Once the inner coils are appropriately positioned, the introducer is carefully withdrawn, while at the same time advancing the shunt so that the outer coil is positioned on the skin of the fetus, within the amniotic cavity. Care must be taken to have suffi cient amniotic fl uid between the for open fetal surgery, and (ii) signifi cant maternal morbidity associated with a large laparotomy. The ultimate hope was that fetoscopic interventions would be possible by a percutaneous approach. Patients are given a preoperative tocolytic agent, often indo- methacin, and also receive prophylactic IV antibiotics. The pro- cedures are performed under local or regional anesthesia. Depending on the gestational age and the tradition of the center, the surgery may be performed in the surgical operating rooms, the labor and delivery operating room, or the ultrasound suite. The endoscopes and fetoscopic instruments have under- gone tremendous development and improvement over the last decade. Operative fetoscopy has now evolved into a combined sono - endoscopic procedure in which the fetal surgical team use both the ultrasound and fetoscopic images simultaneously to perform the operations. Purpose - designed embryo - or feto- scopes typically have remote eyepieces, to reduce weight and facilitate precise movements. Nearly all are bendable fi bre - endoscopes rather than conventional rod lens scopes, and as the number of pixels increases over time, image quality improves. Typical diameters are between 1.0 and 2.0 mm. Thin - walled semi - fl exible plastic cannulas (7 – 10 French diameter) are used to provide access to the amniotic sac and this allows different instruments to be inserted into the uterus without multiple puncture wounds. Ultrasound is used to identify an appropriate entry point and is then used to direct the trochar into the amniotic cavity, avoid- ing the placenta, fetus, and maternal organs such as bowel and bladder. One group has documented the safety, in their hands, of a transplacental approach [10] but most operators still avoid deliberate transplacental passage of instruments if at all possible. Ultrasound is initially used to direct and position the fetoscope within the uterus, since its fi eld and depth of view can be relatively limited. These procedures are truly “ sono - endoscopic ” . One of the most commonly performed fetoscopic procedures is laser ablation of placental blood vessels in twin – twin transfu- sion syndrome (TTTS). In these cases the endoscope is placed into the sac of the recipient twin, which is the sac with polyhy- dramnios. The insertion point of the fetoscope is determined by placental location, the lie of the donor baby, the umbilical cord insertion sites and the presumed membrane and vascular equa- tors between the twins. Once the fetoscope is positioned and the placental surface is being visualized, the whole vascular equator is then explored. Unpaired vessels consistent with abnormal com- munications are ablated using a laser fi ber that is advanced through the operating channel of the endoscope sleeve. After ablation of the abnormal communications the endoscope is with- drawn and the polyhydramnios is then drained through the cannula under ultrasound guidance. Once the fl uid has reached a normal level (deepest vertical pocket of around 5 – 6 cm) the cannula is removed. This amnioreduction reduces the risk of port - site leaking and amniotic fl uid irritation of the peritoneal Chapter 49 702 is based on contraction activity. Frequently no further medica- tion is necessary. Maternal vital signs should be followed carefully as direct observation of the uterine puncture is not possible to determine hemostasis, because of the percutaneous approach. One benefi t of not needing tocolysis is that the hemostatic mech- anism of the uterus in response to a puncture is a localized contraction. In summary, the fact that many fetal and particularly placental procedures can now be performed using microendo- scopes and that hysterotomy is infrequently needed except for a few rare indications, has improved the rate and severity of mater- nal complications. Nevertheless none of these procedures are risk free. There have been intraoperative maternal deaths reported and this must be discussed with a patient and her family in balancing the risks and benefi ts of a prospective intervention. References 1 Golombeck K , Ball RH , Lee H , et al. Maternal morbidity after mater- nal - fetal surgery . Am J Obstet Gynecol 2006 ; 194 ( 3 ): 834 – 839 2 DiFederico EM , Burlingame JM , Kilpatrick SJ , Harrison MR , Matthay MA . Pulmonary edema in obstetric patients is rapidly resolved except in the presence of infection or of nitroglycerin tocolysis after open fetal surgery . Am J Obstet Gynecol 1998 ; 179 : 925 – 933 3 Wilson RD , Johnson MP , Crombleholme TM , et al. Chorioamniotic membrane separation following open fetal surgery: pregnancy outcome . Fetal Diagn Ther 2003 ; 18 ( 5 ): 314 – 320 . 4 Bruner JP , Tulipan NB , Richards WO , Walsh WF , Boehm FH , Vrabcak EK . In utero repair of myelomeningocele: a comparison of endoscopy and hysterotomy . Fetal Diagn Ther 2000 ; 15 ( 2 ): 83 – 88 . 5 Johnson MP , Gerdes M , Rintoul N , et al. Maternal - fetal surgery for myelomeningocele: neurodevelopmental outcomes at 2 years of age . Am J Obstet Gynecol 2006 ; 194 ( 4 ): 1145 – 1150 . 6 Farrell JA , Albanese CT , Jennings RW , Kilpatrick SJ , Bratton BJ , Harrison MR . Maternal fertility is not affected by fetal surgery . Fetal Diagn Ther 1999 ; 14 : 190 – 192 . 7 Wilson RD , Johnson MP , Flake AW , et al. Reproductive outcomes after pregnancy complicated by maternal - fetal surgery . Am J Obstet Gynecol 2004 ; 191 ( 4 ): 1430 – 1436 . 8 Macones GA , Peipert J , Nelson DB , et al. Maternal complications with vaginal birth after cesarean delivery: a multicenter study . Am J Obstet Gynecol 2005 ; 193 ( 5 ): 1656 – 1662 . 9 McMahon MJ . Vaginal birth after cesarean . Clin Obstet Gynecol 1998 ; 41 ( 2 ): 369 – 381 . 10 Yamamoto M , El Murr L , Robyr R , et al. Incidence and impact of perioperative complications in 175 fetoscopy - guided laser coagula- tions of chorionic plate anastomoses in fetofetal transfusion syn- drome before 26 weeks of gestation . Am J Obstet Gynecol 2005 ; 193 ( 3 Pt 2 ): 1110 – 1116 11 Gratacos E , Deprest J . Current experience with fetoscopy and the Eurofoetus registry for fetoscopic procedures . Eur J Obstet Gynecol Reprod Biol 2000 ; 92 : 151 – 160 . 12 Robyr R , Boulvain M , Lewi L , et al. Cervical length as a prognostic factor for preterm delivery in twin - to - twin transfusion syndrome fetus and the wall of the uterus during this procedure to prevent the outer end of the shunt from being left in the myometrium or maternal abdominal wall. In the case of the shunt penetrating the uterus there is the risk of an amnioperitoneal shunt. Shunt place- ment procedures may be the most frequently performed fetal surgical intervention. Complications from shunt placement include maternal and fetal bleeding, placental abruption, amniotic – peritoneal shunt, and infection. Radiofrequency ablation (RFA) is most commonly used for destruction of tumor tissue in solid organs such as the liver. This technique was fi rst used for localized cautery of fetal vascular communications. Additionally it has been used for ablating the feeding vessels to the anomalous fetus in twin reversed arterial perfusion (TRAP) sequence [15,16] . Further applications include selective reduction in monochorionic twin gestations discordant for severe anomalies, and in severe twin – twin transfusion without hope for salvage of one of the twins. The RFA device that we currently use is a 17G needle device (Rita Medical, USA). The perioperative management is identical to that discussed above with shunts except that local anesthesia alone is usually suffi cient. In the case of TRAP, the instrument is guided into the tissue of the acardiac twin at the level of the cord insertion. The prongs are deployed and energy transmission to the device initiated. Because of the heat generation there is out- gassing that is readily visible with ultrasound. The procedure is considered completed when there is no evidence of fl ow in the acardiac twin (or in the cord leading to it) as evidenced by color and pulse Doppler ultrasound. The prongs are then retracted and the device withdrawn. Postoperative monitoring is similar to that used in shunt placement cases and further tocolytic management is rarely necessary. The patients can generally be discharged within hours of the procedure. The risks of complications following shunt placement and RFA are lower than for the more invasive fetal surgical interventions requiring hysterotomy. Obviously, by defi nition, all invasive pro- cedures involve a risk of hemorrhage and infection (Table 49.1 ) [1] . The triggering of preterm delivery by these procedures is also quite unusual, although the risk of PPROM remains. There is also the risk of fetal injury, which in cases of monochorionic twins generally is related to hypotension from acute hypovolemia in the normal cotwin secondary to exsanguination into the placental vascular bed and the other fetus. Over time, as teams have become more comfortable with feto- scopic procedures, the length of hospitalization, complexity of perioperative management and type of anesthesia have changed. In many cases these operations can be performed under ultra- sound guidance as an outpatient procedure (23 - hour admission) with a single dose of indomethacin for tocolysis. Routine preop- erative antibiotic prophylaxis is given. For most procedures spinal or local anesthesia is suffi cient. Postoperative management involves maternal and fetal moni- toring (in cases of fetal viability). Further tocolytic management Fetal Surgery Procedures and Associated Maternal Complications 703 15 Tsao K , Feldstein VA , Albanese CT , et al. Selective reduction of acar- diac twin by radiofrequency ablation . Am J Obstet Gynecol 2002 ; 187 ( 3 ): 635 – 640 . 1 6 L e e H , W a g n e r A J , S y E , e t a l . E f fi cacy of radiofrequency ablation for twin - reversed arterial perfusion sequence . Am J Obstet Gynecol 2007 ; 196 ( 5 ): 459 . treated by fetoscopic laser coagulation of chorionic plate anastomo- ses . Ultrasound Obstet Gynecol 2005 ; 25 : 37 – 41 . 13 Harrison MR , Golbus MS , Filly RA , et al. Management of the fetus with congenital hydronephrosis . J Pediatr Surg 1982 ; 17 ( 6 ): 728 – 742 . 14 Nicolini U , Rodeck CH , Fisk NM . Shunt treatment for fetal obstruc- tive uropathy . Lancet 1987 ; 2 ( 8571 ): 1338 – 1339 . 704 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 50 Cancer in the Pregnant Patient Kenneth H. Kim , David M. O ’ Malley & Jeffrey M. Fowler Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA Introduction The diagnosis of cancer in pregnancy complicates anywhere between 1 in 1000 and 1 in 2000 live births. According to the 2004 Annual National Vitals Statistics Report Provisional Data, malig- nancy is the second most common cause of mortality in repro- ductive - age women aged 25 – 44 years; however, it is a rare cause of maternal death in pregnancy [1,2] . As the trend continues toward delaying childbearing, the incidence of malignancy occur- ring in pregnancy is expected to increase. The most common type of cancer diagnosed during pregnancy is melanoma (complicat- ing approximately 1 in 350 pregnancies), followed by cervical cancer (1 in 2250), Hodgkin ’ s lymphoma (1 in 3000), breast cancer (1 in 7500), ovarian cancer (1 in 18 000), and leukemia (1 in 75 000) [3] . Cancer in pregnancy can be categorized into those discovered during the antenatal period, those discovered at the time of deliv- ery, and those discovered up to 1 year postpartum. In over 50% of cases, cancers complicating pregnancy are found in the post- partum period, within 1 year of delivery. At least one - quarter of cancers are found in the antenatal period, and a small minority are found at the time of delivery [4] . When the diagnosis of a malignant neoplasm is made in preg- nancy, particular care must be taken to balance both maternal and fetal well - being. This often leads to an extremely challenging therapeutic dilemma. In the antenatal period, the clinical picture is simplifi ed if the fetus is mature and can be delivered prior to any treatment initiation, or if the pregnancy is unwanted and the fetus is not viable. When cancer is diagnosed in a desired preg- nancy, and the fetus has not achieved maturity, the clinical situ- ation is more complex. If prognosis is such that delaying treatment will not affect or worsen maternal outcome, treatment may be deferred until the fetus has achieved maturity. However, if the prognosis will deteriorate with a delay in treatment, the risks and benefi ts of more immediate treatment must be weighed against the risks to the pregnancy and the fetus. Certainly, a patient should not be penalized for being pregnant and the necessary steps required to assure appropriate manage- ment and therapy should be taken. Treatment should be indi- vidualized with emphasis on the parents ’ participation in the decision - making process. In addition, a multidisciplinary team must be utilized to ensure that the patient, the physicians, and all else who are involved are well informed of the risks, benefi ts, and alternatives to the treatment choices. It is important to not only consider the medical aspects of the condition but also to consider ethical, moral, spiritual, and cultural issues of the patients. Physicians may be faced with unique psychosocial challenges in addition to the clinical diagnosis of cancer, or fi ndings that are suspicious for cancer in pregnancy. Examples of this may include those patients who are carrying their fi rst, and potentially only pregnancy, or those who have had diffi culties with conception and have undergone assisted reproductive technologies to achieve pregnancy, both cases in which the pregnancy is truly desired. There are also patients that may be opposed to terminating the pregnancy regardless of gestational age for various personal, reli- gious or ethical reasons. The patient ’ s goal may not necessarily be to undergo curative therapy for their malignancy, but to give birth to a healthy infant, no matter what the risk. Some patients may not believe in cesarean delivery for cultural or other reasons and choose to defer any surgery until after delivering vaginally. A small subset may also refuse not only cesarean delivery, but any labor - inducing agents as well, preferring to go into “ natural labor. ” There may be those who refuse blood products of any sort on the basis of religion or culture and may also choose to deliver vaginally, deferring surgery to the postpartum period to reduce the risk of blood loss. In these cases, the patient must be thor- oughly informed of the risks, benefi ts, and alternatives of therapy for their specifi c clinical scenario while heeding their cultural, ethical, religious, and moral beliefs. Cancer in the Pregnant Patient 705 Surgical risks inherent to minimally invasive surgery do not appear to be increased in pregnancy. Laparoscopic techniques in pregnant patients should not differ greatly from that of open procedures. As with open procedures, fetal heart tones should be obtained before and after the procedure. In those cases where the fetus is viable continuous monitoring of the fetal heart rate is advised so that intervention can be undertaken in the event of fetal decompensation. Naso/orogastric decompression should be utilized, and the patient should be placed in a leftward tilt to minimize aortocaval compression. The primary port should be inserted via the open technique or the left upper quadrant direct technique to decrease the risk of uterine perforation or laceration. There has been one reported case of incorrect placement of the Verres needle, leading to pneumoamnion that contributed to fetal loss [15] . Ancillary ports should be placed under direct visu- alization in the cephalad direction, and then rotated carefully. Due to an intra - abdominal space that is progressively compro- mised, laparoscopy should generally not be attempted after 26 – 28 weeks gestation [14] ; however, this should be evaluated on a case - by - case basis. Promising reports of robotic gynecologic surgery are now appearing in the literature but there is no information yet on the use of this novel technique in a pregnant patient to date. Another theoretical risk of laparoscopy is that the developing fetus could potentially be susceptible to acidosis caused by mater- nal absorption of the carbon dioxide gas with subsequent hyper- carbia and serum conversion to carbonic acid. There have been two studies performed in pregnant ewes to evaluate the response in fetal sheep to the use of CO 2 insuffl ation. In the fi rst study [16] , one fetus that was compromised prior to the study succumbed during the pneumoperitoneum. The second study [17] had no such complications. There have been no subsequent reports of fetal loss attributable to acidosis secondary to pneumoperito- neum, and this risk appears to be theoretical. Notwithstanding, if the duration of the case is anticipated to be rather lengthy, it may be prudent to employ traditional open methods of surgery. Until randomized trials are available, the decision of surgical approach should be individualized and made in consultation with the perinatologist and the surgeon, ensuring that the risks, ben- efi ts, and alternatives are discussed at great length with the patient. Cervix In 2007 there will be approximately 11 000 new cases of cervical cancer in the United States with an estimated 3600 deaths from the disease according to the National Cancer Institute. The inci- dence of invasive cervical cancer in pregnancy is low, comprising only approximately 1% of total cervical cancers diagnosed; however, preinvasive cervical neoplasia is quite common in reproductive age women, occurring in 5 – 50 cases per 1000 preg- nancies [18 – 20] . The recent downward trend in the incidence of cervical neoplasia in pregnancy coincides with the general Surgical p rinciples d uring p regnancy While every pregnancy comes with inherent risk such as stillbirth or preterm labor, patients generally never expect to require surgery during this time. It is clear that pregnant patients are not immune to processes that require surgical intervention, whether it be gallbladder disease, appendicitis or invasive cancer. Pregnant patients generally tolerate surgical procedures well, depending on the nature and complexity of the surgery performed. Moreover, the risks of adverse pregnancy outcomes appear to be small when uncomplicated, non - emergent surgical procedures are performed. Nevertheless, the ramifi cations can be grave if the surgery becomes complicated secondary to the clinical scenario (e.g. ruptured viscera) or the procedure itself (e.g. postoperative bleeding, infection or anesthetic complications). Various non - obstetric surgical procedures have been per- formed and reported in the literature. The largest study involves 5405 patients undergoing a large variety of procedures through- out pregnancy, with the majority occurring in the second trimes- ter [5] . This study, which employed the Swedish Birth Registry, observed that the difference in rate of stillbirth and congenital anomalies was insignifi cant, although an increase in the rate of low birth weight and preterm delivery was noted. Factors associated with an increased risk of pregnancy loss include fi rst - trimester surgery, peritonitis, and longer procedure times [6] . Thus if the surgery is needed, recommendations for timing of surgery have generally been to electively defer procedures until the second trimester under controlled circumstances. The use of prophylactic tocolytics at the time of surgery in the second tri- mester has not been shown to decrease the risk of preterm labor or preterm delivery in these patients, but may be benefi cial in the third trimester [7] . However, there are no randomized or pro- spective trials to address this specifi c issue. Clearly, these deci- sions must be individualized for each patient. If the patient is unstable, or requires emergent surgery, this should be carried out in an effi cient, timely manner. When counseling patients it is important to note that intra - abdominal surgery, as opposed to extra - abdominal sites, is associated with a higher risk of preg- nancy - related complications. With advancing technology, the use of minimally invasive laparoscopic and robotic techniques have entered the surgeon ’ s armamentarium. The complexity of the decision to proceed with surgery during the gestation is therefore further layered with what surgical approach to employ. Abundant case reports and studies are present in the literature regarding the well - tolerated nature of laparoscopic surgery during pregnancy [8 – 12] . Benefi ts of the minimally invasive approach include less pain in the postopera- tive period, less use of analgesics, less use of tocolytics, and overall shorter length of bedrest and hospitalization as compared to lapa- rotomy. The most common indications for laparoscopic surgery during pregnancy are cholecystectomy, evaluation of an adnexal mass, and appendectomy [13,14] . Chapter 50 706 Biopsies should be taken of the most suspicious lesions seen at the time of colposcopic evaluation. Multiple biopsies at one examination and use of the endocervical curettage should be avoided [26] . Colposcopic diagnostic accuracy, with or without biopsy, is 95 – 99% and complications rarely arise [27] . The most common complication associated with colposcopically directed biopsy is hemorrhage secondary to the hyperemic state of the cervix during pregnancy. Should this problem present itself, a number of methods can stop the bleeding including direct pres- sure to the site, Monsel solution, silver nitrate, vaginal packing, and/or rarely suture. When the possibility of invasive disease has been excluded, con- servative management with close observation of cervical intraepi- thelial neoplasia is reasonable and acceptable [27 – 32] . While an inadequate colposcopic evaluation is indication for loop electrical excisional procedure (LEEP) or cone biopsy in the non - pregnant patient, this approach can be modifi ed during pregnancy. Pregnant patients with unsatisfactory colposcopic evaluation may undergo repeat colposcopic examination 6 – 12 weeks from the initial col- poscopy. As the transformation zone undergoes further eversion through the gestation, a repeated colposcopy may subsequently yield a satisfactory examination. In pregnancy, the biopsy - proven progression rate from lower - grade to higher - grade dysplasia was found to be approximately 7%, and there was no progression to invasive disease [31] . However, it has also been demonstrated that regression rates of moderate and even severe dysplasia 6 months after delivery appear higher than regression rates in the non - preg- nant population [31,33] . Regression rates in these studies were found to be 68% in patients with CIN 2, and 70% in CIN 3 [31] . Therefore, biopsy - proven dysplasia may be followed with serial colposcopic examinations during pregnancy. The patient may be allowed to have a vaginal delivery, and then followed up 6 – 8 weeks postpartum for defi nitive management. In the pregnant state, LEEP and cone biopsy should be reserved for excluding invasive disease. Risks of these procedures in preg- nancy include cramping, bleeding, infection, preterm premature rupture of membranes, spontaneous abortion and/or preterm labor, and subsequent loss of the pregnancy. Comparatively, the rates of complication with LEEP and cone biopsy are similar [34] . Cold knife cone biopsy may be favored over LEEP to allow for adequate assessment of the margins. If a LEEP or cone biopsy is indicated, this can be performed any time during the fi rst trimes- ter and up to 20 weeks gestational age. If fetal maturity is attain- able in a reasonable amount of time, these procedures can also be deferred until after delivery. Alternatively, cone cerclage, where a McDonald cerclage is placed at the time of conization, has been proposed to try and prevent hemorrhage, preterm labor, and pregnancy loss. While there were no complications in the study, it was quite underpowered, involving only 17 patients [35] . Cervical c arcinoma The occurrence of cervical carcinoma in pregnancy is rare, com- prising only 1% of all cervical cancers diagnosed per year. Presentation will usually be postcoital bleeding or persistent decreasing incidence of cervical cancer. Therefore the practicing obstetrician/gynecologist is more likely to encounter the issue of evaluation and management of an abnormal pap smear rather than management of a pregnant woman with invasive cervical cancer. While Pap smears and routine screening are readily avail- able in developed countries, most patients diagnosed with cervi- cal cancer have not had appropriate screening. Pregnancy and prenatal care affords an opportunity to screen and appropriately treat many patients who would otherwise not seek healthcare. Thus, at the antenatal visit, it is important to stress the impor- tance of cervical neoplasia screening and appropriate follow - up of any abnormal Pap results with colposcopic evaluation, in addi- tion to routine obstetric care. Intraepithelial n eoplasia As many as 5% of pregnancies are complicated by an abnormal Pap smear [20] . Cervical cytology and physical examination, com- plemented with colposcopy, are the mainstay for cervical cancer screening during pregnancy. Studies have shown that use of either spatula - or liquid - based smear methods result in similar detection rates. While an endocervical curettage should be avoided during pregnancy, an endocervical cytology brush should be employed as it improves the adequacy of the smear. Use of the brush may increase the incidence of post - collection spotting, but appears to have no effect on increasing the risk of serious adverse outcomes related to the pregnancy [21] . During pregnancy the emphasis is on evaluation and diagnosis of the extent of neoplasia while defi ni- tive therapeutic management is usually delayed until after delivery. This evaluation of an abnormal Pap smear in the pregnant patient mirrors the management in the non - pregnant state. The Bethesda system remains the standard for classifi cation and management of abnormal cervical cytology. Atypical squa- mous cells of uncertain signifi cance (ASCUS) should be managed in the same manner as in the non - pregnant state with high - risk human papilloma virus (HPV) type testing and colposcopy when indicated, immediate colposcopy, or colposcopy after a repeated abnormal Pap result. Pap smears revealing atypical glandular cells (AGC) of any variety, however rare in pregnancy, warrant further evaluation with colposcopic examination. In the case of AGC, pregnancy complicates the cytologic interpretation with sloughed decidual cells, endocervical gland hyperplasia, and/or cells dem- onstrating an Arias – Stella reaction, all of which are benign changes occurring in normal pregnancy. Compared to non - pregnant counterparts, AGC found in pregnancy may have decreased probability of being associated with malignancy, but should still be followed closely [22 – 25] . Patients who are found to have low - or high - grade intraepithelial lesions, or any other results that cannot exclude high - grade disease, must also undergo colposcopic evaluation. Colposcopic evaluation, which is facilitated in pregnancy by the fact that the transformation zone is everted, should be per- formed when indicated by the Pap cytology. Colposcopy should be performed by clinicians who are familiar with the cervical cytological and colposcopic changes associated with pregnancy. Cancer in the Pregnant Patient 707 demonstrated relative success with delivery once fetal maturity is obtained and delaying cancer therapy until that time or until the postpartum period, even if the cancer is diagnosed at an early gestational age [40,45,46] . Although the risk of recurrence is low in these relatively small case series, the recurrence rate of cervical cancer after intentional delay of treatment to optimize fetal matu- rity cannot be quantifi ed. Thus, if the pregnancy is desired, the patient must be thoroughly counseled on this unquantifi able but likely low risk of recurrence if therapy were to be delayed. If the malignancy is diagnosed in the latter half of the pregnancy, treat- ment can likely be delayed with only slight risk of progression and worsened outcome. With advancing neonatal intensive care technology, the threshold for fetal maturity will continue to decrease, and patients who present at less than 20 weeks will likely have improved risk/benefi t ratio with delay of treatment. In those patients who are diagnosed in the fi rst half of the gestation, and wish to terminate the pregnancy and future fertility, immediate treatment may be offered and recommended. The majority of patients diagnosed with invasive disease in pregnancy will be stage Ia2 to Ib1; in these patients, and those with up to stage IIA disease, standard treatment is usually radical hysterectomy with pelvic lymphadenectomy. Care must be taken in evaluating pelvic lymph nodes as they may contain decidual reaction from the pregnancy which can be confused with metastatic cells. Depending on the size of the uterus at the time of surgery, hysterectomy can be performed with the fetus in utero , or a hysterotomy may be performed immediately preceding hysterectomy. Defi nitive radi- ation therapy offers similar cure rates in these stages of disease; however, this has been avoided mainly secondary to the potential adverse effects of therapeutic radiation. Defi nitive surgical man- agement is associated with baseline perioperative morbidity but offers the advantage of surgical staging and preservation of ovarian function. Use of defi nitive radiation therapy exposes the ovaries, vagina, gastrointestinal and urinary tracts to high doses of radiation, leading to loss of ovarian function and risk of long - term chronic toxicity [47] . Mode of delivery with concomitant cervical cancer remains a controversial topic. There appears to be a slight trend toward worsening prognosis in vaginal deliveries through a cancerous cervix yet this is not well established [36,37,48] . A bulky, friable cervix is at risk for signifi cant complications with life - threatening intrapartum and/or postpartum hemorrhage that may lead to emergent hysterectomy in a less than ideal, uncontrolled and acute situation. In addition, case reports describe recurrence at the episiotomy site, most of which occurred within 6 months of delivery [49,50] . Thus close follow - up with careful palpation and inspection of any laceration or episiotomy site is recommended; if recurrence at this site is noted, management should entail exci- sion followed by radiation therapy. Vaginal delivery should likely be reserved for intraepithelial lesions and potentially early stage I candidates who wish to preserve pregnancy and fertility. Consequently, most clinicians favor abdominal delivery, espe- cially if radical hysterectomy with lymphadenectomy is indicated and can be performed at the time of cesarean delivery. bleeding during pregnancy, but many patients will be asymptom- atic. The vast majority of patients with cervical cancer found in pregnancy will be diagnosed with stage I disease. In the past it was thought that pregnancy altered the course of cervical cancer compared with non - pregnant cohorts. However, it has been dem- onstrated that there is no difference in survival outcomes when matched cohorts were studied [33,36,37] . When compared with non - pregnant counterparts, pregnant patients with cervical cancer are over three times more likely to be stage I, the majority having stage IB disease [36,38 – 41] . Because of the physiologic and anatomic changes that develop with pregnancy, indurations or nodularities at the base of the broad ligament will be less promi- nent during pregnancy, thus risking underestimation of the degree of involvement during staging of the tumor. Regardless, studies have shown that pregnancy does not affect overall survival rate when compared to non - pregnant women, with survival rates of 80% in pregnant subjects compared with 82% in non - pregnant control cohorts [42] . Cervical cancer is primarily staged by physical examination, but disease extent may be diffi cult to determine in the pregnant state. Ancillary studies that may aid in the evaluation of the extent of tumor involvement include limited CT scans of the lower abdomen and pelvis. Sigmoidoscopy and cystoscopy are safe in pregnancy for the evaluation of mucosal involvement, and, in some cases, MRI has been utilized to help determine the extent of urinary tract involvement [43,44] . Once staging has been determined, management must be indi- vidualized for each patient. A multidisciplinary team, which includes perinatologist, neonatologist, and gynecologic oncolo- gist, should be recruited to extensively counsel the patient on all of the treatment options available to her. These should take into account the tumor stage, her prognosis with immediate treatment versus delayed treatment, and the fetal issues including timing of delivery. The patient ’ s desire to continue or terminate the preg- nancy may impact treatment decisions. In most instances of inva- sive cancer, relatively prompt treatment is expected and ideal. During pregnancy, effecting defi nitive treatment will depend on the stage of disease and the gestational age of the fetus. Microinvasive disease may be suspected after colposcopy; however, the diagnosis is formally made only after cervical con- ization. If it is determined the patients has International Federation of Gynecology and Obstetrics (FIGO) stage Ia1 disease, she can be followed closely and delivered as obstetrically indicated with defi nitive management deferred to the postpartum period. However, if there is evidence of frank invasion (FIGO stage Ia2 or higher), further options must be discussed with the patient regarding defi nitive management, particularly if the patient desires to continue the pregnancy. Standard management for the non - pregnant patient would be prompt defi nitive therapy. However, with informed consent, the pregnant patient can be followed with close observation with defi nitive therapy deferred until after delivery once fetal maturity is attained. Fortunately, most pregnant patients diagnosed with cervical cancer have early stage disease. Case reports and small series have Chapter 50 708 rics. Prior to routine ultrasonography, these masses were usually found at the time of abdominal delivery, during the postpartum period, or during the gestation when associated symptoms prompted a physical exam. Currently, many asymptomatic masses that would otherwise be unrecognized are incidentally found at the time of fi rst - trimester sonogram. The actual inci- dence is not well documented since many masses that are inci- dentally discovered in pregnancy undergo regression, are not reported, or may not require/receive any intervention. It has been estimated that 0.2 – 2% of pregnancies are complicated by an adnexal mass, and that approximately 1 – 3% of these are malig- nant [56 – 63] . While a signifi cant portion of these masses are benign corpus luteum and other cysts that will undergo sponta- neous regression by the second trimester, a proportion of these masses will be neoplastic and persist through the second trimester and beyond, potentially causing major complications during the pregnancy. Some of these will need extensive surgical intervention. It has been demonstrated that approximately three - quarters of adnexal masses found in pregnancy are simple - appearing cysts measuring less than 5 cm in diameter. The remaining one - quarter of adnexal masses discovered in pregnancy are either simple or complex, and measure greater than 5 cm in diameter. Of all adnexal masses found in pregnancy, 70% will spontaneously resolve by the early middle trimester, becoming undetectable by 14 – 15 weeks gestational age [59,64] . Functional cysts, including theca lutein cysts, are the most common masses detected, while dermoid cysts are the most common neoplasm encountered in pregnancy. Other common benign fi ndings are cystadenomas, paraovarian cysts, endometriomas, and leiomyomas [64 – 66] . Adnexal masses measuring greater than 8 cm are at risk of complications, including pain, torsion, rupture, and hemorrhage. A minority of pregnant women with an adnexal mass will have an acute presentation where surgery is clearly indicated [67 – 69] . Rarely a mass can be associated with preterm labor, preterm premature rupture of membranes, pregnancy loss, obstruction of labor, and/or fetal/neonatal death [66,68,69] . The risk of torsion peaks in two periods during the pregnancy: the fi rst trimester or early second trimester, when the uterus is growing out of the true pelvis; and the puerperium, when the uterus undergoes rapid involution. If a patient develops clinical signs or symptoms con- sistent with torsion, emergent surgery is indicated and should not be delayed, regardless of gestational age. In the non - emergent setting, ultrasound, occasionally supple- mented with other imaging modalities, has been traditionally used to guide management decisions. Generally, if the mass appears benign on ultrasonographic evaluation, it is extremely unlikely to be malignant. Tumor markers including AFP, LDH, hCG, and CA - 125 levels may be elevated with pregnancy and are generally not reliable or useful. If the origin of the mass is not clear, occasionally, magnetic resonance imaging can be employed to differentiate between ovarian versus other possible sources. Masses that are simple and cystic in nature and which measure less than 6 cm have a low risk of malignancy (less than 1%) and For the subset of patients with early - stage tumors who wish to defer defi nitive treatment until the postpartum period and who wish to conserve fertility, radical trachelectomy performed vagi- nally or abdominally may be a viable option [51] . A total of 212 patients collected from six studies were evaluated for survival, fertility and pregnancy outcomes after radical trachelectomy. Of these 212 patients, 2% developed recurrence, and 56% delivered a viable pregnancy with 28% being full term, and 28% being preterm [52,53] . Advanced - stage cervical cancer is rare in pregnancy and there is a paucity of data in the literature regarding management. For higher - stage disease and those few patients who are medically unfi t for surgery, radiation therapy with concurrent chemother- apy is indicated. If this occurs in the third trimester, delay of therapy until after delivery is reasonable [46] . If the patient chooses not to continue the pregnancy, external - beam radiation with concomitant chemotherapy can be given in the fi rst trimes- ter, and if spontaneous miscarriage does not occur, dilation and curettage or extraction can be performed. In the middle trimes- ter, abortion may be induced or delayed, depending on spiritual/ religious, moral, and ethical considerations. If delayed, telether- apy may be administered; however, hysterotomy may be required for up to one - fourth of cases [45] . One week post - abortion, after uterine involution, external radiation can be administered, fol- lowed by brachytherapy. In general, the anatomic distortion that occurs in pregnancy must be taken into consideration to ensure that the radiation fi eld includes all targeted regions. The use of neoadjuvant chemotherapy without radiation may be helpful in the pregnant patient [54] . The most important factor in admin- istration of the chemotherapy during pregnancy is the gestational age of the fetus. If the fetus is exposed to chemotherapeutic agents within 2 weeks postconception, it will either spontaneously abort or develop normally. Organogenesis occurs in the fi rst trimester; thus, chemotherapy should be avoided during this period, as this is the most likely time that the fetus will develop a malformation. Though limited, reports have shown relative success with admin- istration of chemotherapy during the second and third trimesters, with very low risk of fetal malformations; however, there has been increased tendency toward interuterine growth restriction, low birth weight, spontaneous abortion, and/or preterm labor. Timing of chemotherapy administration with relation to the planned delivery date is also important. Chemotherapy given within 3 weeks of delivery may lead to maternal myelosuppres- sion with resultant neutropenia, thrombocytopenia, and/or anemia. Furthermore, the neonate may be incapable of handling such high levels of chemotherapeutic agents and metabolites because of its immature hepatorenal excretion mechanisms [55] . Management of a dnexal m asses o ccurring in p regnancy The fi nding of an adnexal mass during pregnancy has increased as ultrasound has become commonplace in the practice of obstet- . and Genetics, Departments of Obstetrics, Gynecology and Reproductive Sciences, UCSF Fetal Treatment Center, University of California, San Francisco, CA, USA 2 Department of Obstetrics and. 1982 ; 17 ( 6 ): 728 – 742 . 14 Nicolini U , Rodeck CH , Fisk NM . Shunt treatment for fetal obstruc- tive uropathy . Lancet 1987 ; 2 ( 8571 ): 1338 – 1339 . 704 Critical Care Obstetrics, 5th. 699 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy.