31.Vonderheide RH, Thadhani R, Kuter DJ. Association of thrombocytopenia with the use of intra-aortic balloon pumps. Am J Med 1998;105(1):27–32.

32.Jaron D, Ohley W, Kuklinski W. Efficacy of counterpulsation: model and experiment. Trans Am Soc Artificial Inter Organs 1979;25:372–377.

33.Jaron D, Moore TW, He P. Theoretical considerations regarding the optimization of cardiac assistance by intraaortic balloon pumping. IEEE Trans Biome Eng 1983;30(3):177–185.

34.Jaron D, Moore TW, He P. Control of intraaortic balloon pumping: theory and guidelines for clinical applications. Ann Biomed Eng 1985;13(2):155–175.

35.Niederer P, Schilt W. Experimental and theoretical modelling of intra-aortic balloon pump operation. Med Biol Eng Comput 1988;26(2):167–174.

36.Barnea O, Smith B, Moore TW, Jaron D. Simulation and optimization of intra-aortic balloon pumping. Proceedings. Computers in Cardiology (Cat. No.89CH2932-2). Los Alamitos (CA): IEEE Computer Society Press; 1990. p 237–240.

37.Sakamoto T, et al. Effects of timing on ventriculoarterial coupling and mechanical efficiency during intraaortic balloon pumping. ASAIO Journal 1995;41(3):M580–MM583.

38.Weller PR, Morrow DR, LeFe`vre JE. Evolution of a fuzzy controller for the intra-aortic balloon pump. Proceedings of 2nd European Medical and Biological Engineering Conference, EMBEC’02, Vienna, Austria, Hutten H, Krosl P. editors. ISBN 3-901351-62-0;4–8. December 2002; p 1588–1589.

39.Kane GR, Clark JW, Bourland HM, Hartley CJ. Automatic control of intra-aortic balloon pumping. Trans Am Soc Artif Int Organs 1971;17:148.

40.Martin PJ, Jaron D. New controller for in-series cardiac-assist devices. Med Biol Eng Computing 1978;16(3):243–249.

41.Barnea O, Smith B, Moore TW, Jaron D. An optimal control algorithm for intra-aortic balloon pumping. Images of the Twenty-First Century. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society (Cat. No.89CH2770-6). New York: Vol. 5.

IEEE; 1989. p 1419–1420.

42. Barnea O, et al. Optimal controller for intraaortic balloon pumping. IEEE Trans. Biomed Eng 1992;39(6):629– 634.

43.Smith B, Barnea O, Moore TW, Jaron D. An algorithm for optimal control of the intra-aortic balloon pump. Proceedings of the Fifteenth Annual Northeast Bioengineering Conference (Cat. No.89-CH2689-8). New York; IEEE. 1989; p 75–76.

44.Zelano JA, Li JK, Welkowitz W. A closed-loop control scheme for intraaortic balloon pumping. IEEE Trans Biomed Eng 1990;37(2):182–192.

45.Kantrowitz A, et al. Initial clinical trial of a closed loop, fully automatic intra-aortic balloon pump. ASAIO Journal 1992; 38(3):M617–M621.

46.Sakamoto T, Arai H, Maruyama T, Suzuki A. New algorithm of intra aortic balloon pumping in patients with atrial fibrillation. ASAIO Journal 1995;41(1):79–83.

Further Reading

Goldberger M, Tabak SW, Shah PK. Clinical experience with intra-aortic balloon counterpulsation in 112 consecutive patients. Am Heart J 1986;111(3):497–502.

McEnany MT, et al. Clinical experience with intraaortic balloon pump support in 728 patients. Circulation 1978;58(3 Pt 2):I124– I132.

See also ARTERIES, ELASTIC PROPERTIES OF; HEMODYNAMICS; VASCULAR GRAFT PROSTHESIS.

INTRACRANIAL PRESSURE MONITORING. See

MONITORING, INTRACRANIAL PRESSURE.

INTRAOCULAR LENSES. See LENSES, INTRAOCULAR.

INTRAOPERATIVE RADIOTHERAPY. See

RADIOTHERAPY, INTERAOPERATIVE.

INTRAUTERINE DEVICES (IUDS). See

CONTRACEPTIVE DEVICES.

INTRAUTERINE SURGICAL TECHNIQUES

JOSEPH P. BRUNER

Department of Obstetrics and

Gynecology

Nashville, Tennessee

R. DOUGLAS WILSON

N. SCOTT ADZICK

University of Pennsylvania

Philadelphia, Pennsylvania

LOUISE WILKINS-HAUG

AUDREY C. MARSHALL

Women’s and Children’s Hospital

Boston, Massachusetts

RUBEN A. QUINTERO

Florida Institute for Fetal

Diagnosis and Therapy

Tampa, Florida

M. YAMAMOTO

Y. VILLE

University of Paris

Paris, France

ANTHONY JOHNSON

University of North Carolina

Chapel Hill, North Carolina

JULIE S. MOLDENHAUER

Wayne State University

Detroit, Michigan

INTRODUCTION

Intrauterine surgery of the fetus or fetal adnexae is spreading rapidly throughout the world. In a broad sense, intrauterine surgery includes any procedure in which a medical device is purposely placed within the uterine cavity. For most physicians, however, the concept of intrauterine surgery excludes such commonly performed procedures as amniocentesis and chorionic villous sampling. Rather, the term usually refers to techniques requiring specialized knowledge, experience, and most especially, instrumentation. Procedures most commonly mentioned in discourses on intrauterine surgery include those specifically developed for the treatment of such serious anatomic defects as congenital cystic adenomatoid malformation (CCAM), sacrococcygeal teratoma (SCT), lower urinary tract obstruction (LUTO), myelomeningocele, aortic or pulmonic stenosis, gastroschisis, iatrogenic amniorhexis, twin-to- twin transfusion syndrome (TTTS), and twins discordant for severe anomalies. As no one person in the world is an expert in every one of these procedures, the remainder of

172 INTRAUTERINE SURGICAL TECHNIQUES

this chapter is divided into individual sections, each authored by someone widely recognized as a leader in the treatment of that particular anomaly.

CONGENITAL CYSTIC ADENOMATOID MALFORMATION AND SACROCOCCYGEAL TERATOMA

Most prenatally diagnosed malformations are managed by appropriate medical and surgical evaluation and treatment following planned delivery near term, with some cases requiring transfer of the mother to a tertiary referral center with obstetrics, maternal fetal medicine, medical genetics, neonatology, and pediatric surgery subspecialties. Certain anatomic abnormalities can have significant fetal developmental consequences, with emergency in utero therapy being required due to gestational age and mortality risks for the fetus. Open maternal fetal surgery poses additional risks to the mother. Maternal fetal surgery (1–4) should not be attempted until (1) the natural history of the fetal disease is established by following up on untreated cases, (2) selection criteria for cases requiring intervention are developed, (3) pathophysiology of the fetal disorder and its correction are defined in fetal animal models, and (4) hysterotomy and fetal surgery can be performed without undue risk to the mother and her reproductive potential.

Congenital cystic adenomatoid malformation of the lung (CCAM) (5) is a rare lesion characterized by a multicystic mass of pulmonary tissue with proliferation of bronchial structures. CCAM is slightly more common in males and is unilobar in 80–95% of cases. CCAMs derive their arterial blood supply from the normal pulmonary circulation. CCAMs are divided clinically into cystic and solid lesions, but have been divided traditionally into three types based on their pathological characteristics. Type 1 CCAM lesions account for 50% of postnatal CCAM cases and consist of single or multiple cysts lined by ciliated pseudostratified epithelium (5). These cysts are usually 3–10 cm in size and 1–4 in number (5). Type II CCAM lesions account for 40% of postnatal cases of CCAM and consist of more numerous cysts of smaller diameter, usually less than 1 cm. They are lined by ciliated, cuboidal, or columnar epithelium (5). Type III CCAM lesions account for only 10% of CCAM cases and are usually large, homogenous, microcystic masses that cause mediastinal shift. These lesions have bronchiolar-like structures lined by ciliated cuboidal epithelium separated by masses of alveolar-sized structures lined by nonciliated cuboidal epithelium (5). Prognosis in Type III CCAM is related to size.

Sacrococcygeal teratoma (SCT) (6) is defined as a neoplasm composed of tissues from either all three germ layers or multiple foreign tissues lacking an organ specificity. SCT is thought to develop from a totipotent somatic cell originating in Hensen’s node. SCT has been classified by the relative amounts of presacral and external tumor present, with Type I completely external with no presacral component, Type II external component with internal pelvic component, Type III external component with internal component extending into the abdomen, and Type IV completely internal with no external component (7). A Type I SCT is evident at birth and is usually easily resected and

has a low malignant potential (6). Type II and III SCTs are recognized at birth, but resection may be difficult requiring an anterior and posterior approach (6). A Type IV SCT can have a delayed diagnosis until symptomatic at a later age

(6). SCT is one of the most common tumors in newborns and has an incidence of 1 per 35,000 to 40,000 live births (6).

Evaluation of the fetal status for CCAM and SCT requires multiple imaging and functional techniques (8–10), including fetal ultrasound, fetal MRI, and fetal echocardiogram with arterial and venous Doppler assessments (umbilical artery, umbilical vein, ductus venosus). Measurements include combined cardiac output, cardiothoracic ratio, descending aortic blood flow, inferior vena cava diameter, placental thickness, umbilical artery systolic to diastolic Doppler ratio, and amniotic fluid index. Presence of ascites, pleural or pericardial effusion, and skin or scalp edema are important markers for the extent of fetal hydrops and its overall effect on fetal stability. Specific ultrasound imaging of the CCAM and SCT looks for the percentage of cystic and solid components in the tumors as well as an overall mass volume (cc) estimate (AP cm transverse cm height cm 0.52). The SCT consistency and size can be reflected directly in the combined cardiac output and amount of vascular shunting. The CCAM overall size can cause mediastinal shift with cardiac dysfunction and pulmonary deformation. Validated ratio of CCAM/head circumference (CVR) can be used for prognosis and follow-up planning (10). The specific lobar location for the CCAM may have a differential impact on cardiac function. The development of fetal hydrops is due mainly to cardiac dysfunction secondary to compression.

The physiologic changes required in the fetal status to move from expectant management to open maternal fetal surgery is generally dictated by fetal (gestational age and extent of fetal hydrops) and maternal factors (8–10). Criteria for consideration of maternal fetal surgery for CCAM resection (fetal lobectomy) require the absence of maternal risk factors for anesthesia and surgery, a singleton pregnancy with a normal karyotype (amniocentesis, chorionic villus sampling, or percutaneous umbilical blood sampling), no other anatomical abnormalities beyond the associated hydrops, gestational age of 21–31 weeks, and massive multicystic or predominantly solid CCAM (CVR > 1.6) (8–10). In selected cases, the failure of in utero therapy techniques, such as thoracoamniotic shunting or cyst aspiration for the large Type I lesions, to reverse the fetal hydrops would be required. Criteria for consideration of maternal fetal surgery for debulking of a SCT require the absence of maternal risk factors for anesthesia and surgery, a singleton pregnancy with a normal karyotype, the absence of significant associated anomalies, evidence of impending high output cardiac failure, gestational age of 21–30 weeks, and favorable SCT anatomy classification (Type I or II) (9).

The technique for maternal hysterotomy to allow access to the fetus has been well described and has evolved over 25 years of experimental and clinical work (1,8,9). The uterus is exposed through a maternal low transverse abdominal incision. If a posterior placenta is present, superior and inferior subcutaneous flaps are raised and a vertical midline fascial incision is made to expose the uterus for a convenient anterior hysterotomy with the uterus remaining

in the abdomen. Conversely, the presence of an anterior placenta necessitates the division of the rectus muscles so the uterus can be tilted out of the abdomen for a posterior hysterotomy. A large abdominal ring retractor (Turner– Warwick) is used to maintain exposure and prevent lateral compression of the uterine vessels. Sterile interoperative ultrasound is used to delineate the fetal position and placental location. The edge of the placenta is marked under sonographic guidance using electrocautery or a marking pen. The position and orientation of the hysterotomy is planned to stay parallel to and at least 6 cm from the placental edge but still allow exposure of the appropriate fetal anatomy. The hysterotomy is facilitated by the placement of two large monofilament sutures (PDS II 1 Ethicon; Somerville, NJ) parallel to the intended incision site and through the full thickness of the uterine wall and membranes under sonographic guidance. The electrocautery is used to incise the myometrium between the two stay sutures down to the level of the amniotic membranes. A uterine stapler device (US Surgical Corporation; Norwalk, CT) with absorbable Lactomer staples is then directly introduced through the point of fixation and into the amniotic cavity by using a piercing attachment on the lower limb of the stapler. The stapler is fired, thereby anchoring the amniotic membranes (chorion, amnion) to the uterine wall creating a hemostatic hysterotomy. Careful evaluation for the membrane adhesion status and for any myometrial bleeding sites is undertaken. If required, interrupted PDS sutures are used to control bleeding and membrane separation. The fetus and the internal uterine cavity are continually bathed in warmed lactated Ringers at 38–408C using a level I warming pump connected to a red rubber catheter that is placed in the uterine cavity through the hysterotomy.

For CCAM resection (1,8,11), once the appropriate fetal area is visualized in the hysterotomy site, the fetal arm is brought out for pulse oximeter monitoring, IV access, and fetal position control. Intraoperative fetal echocardiography is used throughout to monitor cardiac function. The fetal chest is entered by a fifth intercostal space thoracotomy. The lesion usually decompresses out through the thoracotomy wound consistent with the increase in the thoracic pressure from the mass (8). Using techniques initially developed on experimental animals, the appropriate pulmonary lobes containing the lesion are resected (1,11). Fetal resuscitation is performed if needed through intravenous administration of crystalloid, blood, and codeblue medications with fetal echocardiography providing functional information. The fetal thoracotomy is closed and the fetal arm is returned to the uterus.

The technique for debulking of an external fetal SCT has been described in detail previously (1,9,12,13). The fetal foot is used for pulse oximeter monitoring and IV access with intraoperative echocardiography. The fetal SCT is exposed and a Hagar dilator is placed in the rectum. Fetal skin is incised circumferentially around the base of the tumor and a tourniquet is applied to constrict blood flow. The tumor is debulked externally, usually with a 90 mm thick tissue stapler (US Surgical Corporation; Norwalk, CT). The objective of the fetal SCT resection is to occlude the tumor vascular supply and remove the low resistance

tumor vascular bed from the fetal circulation. No attempt is made to dissect the intrapelvic component of the tumor or to remove the coccyx (done with a second procedure after birth). Fetal resuscitation is performed if needed through intravenous administration of crystalloid, blood, and codeblue medications with fetal echocardiography providing functional information. The fetal sacral wound is closed.

Repair of the hysterotomy after fetal surgery (1–4) uses a water-tight two-layered uterine closure, with interrupted full thickness stay sutures placed first and untied using PDS II 1 (Ethicon; Somerville, NJ), and the uterus is then closed with a running continuous stitch PDSII 0 (Ethicon; Somerville, NJ) including the chorion-amnion membrane layer. The interrupted stay sutures are then tied after the amniotic fluid volume has been corrected with warm lactated Ringers through a red rubber catheter and volume confirmed by ultrasound visualization. The omentum is sutured in place over the hysterotomy closure to help seal the hysterotomy site with vascularized tissue and to prevent bowel adherence to the site, especially when a posterior hysterotomy is performed. The maternal laparotomy incision is closed in layers. It is important to use a subcuticular skin closure covered with a transparent dressing so that monitoring devices can be placed on the maternal abdomen postoperatively.

In some specific cases, when the CCAM lesion is not resected in utero, it continues to be a large space-occupying lesion with mediastinal shift. Thus, it might be anticipated that respiratory compromise will be present at birth, the delivery may be facilitated with an EXIT procedure (ex utero intrapartum therapy) (14). Uterine relaxation is maintained by high concentration inhalational anesthetics, with additional tocolysis if necessary. The EXIT requires only the head and chest to be initially delivered through, preferably, a low transverse hysterotomy wound thereby preserving uterine volume with the lower fetal body and continuous warmed lactated Ringers infusion to prevent cord compression. These maneuvers preserve the uterine-placental circulation and continue placental gas exchange. The EXIT procedure can be done through an anterior or posterior hysterotomy, but its location in the uterus may require that all future pregnancies be delivered by cesarean section with no trial of labor if a low anterior transverse location is not available.

All future pregnancies following maternal hysterotomy for maternal-fetal surgery require cesarean section at term with no trial of labor. Maternal obstetrical risks in a subsequent pregnancy are similar to risks following for a classic cesarean section (15).

LOWER URINARY TRACT OBSTRUCTION

The diagnosis and treatment of fetal lower urinary tract obstruction (LUTO) requires knowledge of the differential diagnosis and the natural history of the condition, a thorough understanding of the criteria for therapy, and management expertise. Fetal LUTO is one of the most commonly diagnosed birth defects. Untreated, and depending on the level of the obstruction, it may lead to hydronephrosis, renal dysplasia, pulmonary hypoplasia, and

174 INTRAUTERINE SURGICAL TECHNIQUES

perinatal death (16,17). The prognosis depends on the extent of preexisting renal damage and the effectiveness of therapy. Treatment with fetal urinary diversion procedures is aimed at preventing renal damage and pulmonary hypoplasia (18–20).

Obstruction to urine flow has been shown in animal models to result in hydronephrosis and renal dysplasia (21). Release of the obstruction is associated with no or variable renal damage depending on the timing of the release or the creation of the defect (21,22). Pulmonary hypoplasia is another major potential complication of fetuses with obstructive uropathy (23). The association probably results from the attendant oligohydramnios.

Urethral obstruction may result from posterior urethral valves (PUV), anterior urethral valves, megalourethra, urethral duplications, urethral atresia, obstructive ureterocele, or cloacal dysgenesis. Posterior urethral valves (PUV), first described by Young et al. (24), constitute the most common cause of lower urinary tract obstruction in male neonates, with an incidence of 1:8000 to 1:25,000 livebirths (25). The lesions occur only in males because the female counterpart of the verumontanum, from which the valves originate, is the hymen.

In utero therapy is usually limited to fetuses with bladder outlet obstruction. Fetuses with unilateral obstruction are not typically considered candidates for in utero therapy, regardless of the magnitude of the obstruction or renal findings. In these patients, the risk/benefit ratio of in utero intervention favors expectant management, even if it means loss of the affected renal unit.

Fetal renal function may be assessed by analysis of fetal urinary parameters via vesicocentesis. Patients are considered candidates for in utero therapy if fetal urinary parameters are below the threshold for renal cystic dysplasia. If the values are above the threshold, therapy should not be offered.

The application of selection criteria in patients with fetal LUTO for possible in utero therapy results in a significant attrition rate. Disqualification from therapy may result both from ‘‘too healthy’’ or ‘‘too sick’’ conditions. Examples of too healthy conditions include normal amniotic fluid volume or suggestion of nonobstructive dilatation of the urinary tract. Examples of too sick conditions include sonographic evidence of renal cystic dysplasia, abnormal fetal urinary parameters, abnormal karyotype, or the presence of associated major congenital anomalies. Of 90 patients referred to the Florida Institute for Fetal Diagnosis and Therapy from October 1996 to October 2003, more than one-half were disqualified from therapy from single or overlapping conditions.

Percutaneous ultrasound-guided vesicoamniotic shunting of fetuses with LUTO began in the early 1980s (16,19,23). The goal of therapy is to avoid development of pulmonary hypoplasia from the attendant oligohydramnios as well as to preserve renal function. Fetal bladder shunting should be offered only to patients without sonographic or biochemical evidence consistent with renal cystic dysplasia, normal karyotype, and lack of associated major congenital anomalies.

The procedure can be performed under local, regional, or general anesthesia. A minimal skin incision is made.

Ultrasound is used to identify the ideal site of entry into the fetal bladder, below the level of the umbilicus. Color Doppler ultrasonography is used to identify the umbilical vessels around the distended bladder and avoid them. Under ultrasound guidance, the trocar is directed through the maternal tissues and up to the fetal skin. Fetal analgesia is achieved with pancuronium 0.2 mg/kg and fentanyl 10 mcg/kg. The trocar stylet is used to enter the fetal bladder with a sharp, swift, and controlled maneuver. If a prior vesicocentesis had been performed, it is advisable to obtain a sample of fetal urine for microbiological purposes to rule out preexisting infection. A sample of fetal urine is sent for further biochemical testing. Placement of the double-pigtail catheter is monitored with ultrasound. After the distal loop is deployed in the bladder, the trocar is retrieved to the level of the bladder wall. A small amount of the straight portion of the catheter may be advanced into the bladder to avoid retracting the distal loop into the bladder wall. The trocar shaft is retrieved slowly while simultaneously maintaining pressure on the catheter to deploy the straight portion within the bladder wall and fetal skin. Once the shaft of the trocar reaches the fetal skin, entrance of the catheter, including the proximal loop, can be safely deployed. If complete anhydramnios is present prior to insertion of the catheter, it is advantageous to attempt an amnioinfusion with an 18 gauge needle prior to shunting to create the space for deployment of the proximal loop. Amnioinfusion is aimed at preventing misplacement of the proximal loop within the myometrium and fetal membranes.

Despite adequate placement, malfunction of vesicoamniotic shunting may occur up to 60% of the time (26). The shunt may pull from the skin into the fetal abdomen, resulting in iatrogenic ascites, or out of the fetal bladder, with no further drainage of urine. The shunt may pull out of the fetus altogether as well. Replacement of the shunt is associated with an additive risk of fetal demise, chorioamnionitis, premature rupture of membranes, and miscarriage or preterm delivery, for a total perinatal loss rate of approximately 5% per instance.

In 1995, we proposed the use of endoscopy to assess the fetal bladder for diagnostic and surgical purposes (27,28). Endoscopic visualization of the fetal bladder with a larger endoscope can be justified during vesicoamniotic shunting. Currently, we use a 3 mm or a 3.9 mm trocar with a 2.7 mm or 3.3 mm diagnostic or operating endoscope. This diameter is slightly larger than the 14 gauge (approximately 2.1 mm) needle used for the insertion of the dou- ble-pigtail catheter. Access to the fetal bladder allows remarkable evaluation of the bladder, ureteral orifices, and urethra as well as the opportunity to perform surgical procedures.

In normal fetuses, the urethra is not dilated, appearing as a small hole within the bladder. In patients with a true urethral obstruction, endoscopy will show a variable dilatation of the urethra at the level of the bladder neck. The urethra is located using a 258 or a 708 diagnostic rigid endoscope. Alternatively, a flexible/steerable endoscope may be used. The anatomical landmarks to identify at this level include the verumontanum and the urethral valves. The diagnostic endoscope is then exchanged for a rigid

operating endoscope. A 600 mm YAG-laser fiber is passed through the operating channel of the endoscope, and then ablated using 5–10 w and 0.2 s pulses in successive steps. The fiber is placed as anterior and medial as possible. It is not necessary to evaporate the entire valvular tissue. Instead, only a few defects to either side of the midline are necessary to establish urethral patency (27,29). The dilated urethra may collapse intraoperatively once patency is re-established, which may obscure the field of view and require frequent instillation of saline to the side port of the trocar to distend it. Color Doppler may also be used to document fetal urination through the penis.

A urethrorectal fistula may occur from thermal damage beyond the posterior wall of the urethra into the perirectal space. To avoid this complication, only 5– 10 w of energy in short bursts should be used while ablating the valves.

The management of fetuses with lower obstructive uropathy continues to be one of the most challenging subjects in fetal therapy. The difficulties include establishing the correct differential diagnosis, accurately predicting subsequent renal function, and providing the best treatment.

MYELOMENINGOCELE

Myelomeningocele results from the failure of caudal neural tube closure during the fourth week of gestation. The lesion is characterized by protrusion of the meninges through a midline bony defect of the spine, forming a sac containing cerebrospinal fluid and dysplastic neural tissue. Affected infants exhibit varying degrees of somatosensory loss, neurogenic sphincter dysfunction, paresis, and skeletal deformities (30). Virtually all such infants also have the Chiari II malformation, and up to 95% develop hydrocephalus (31). Although myelomeningocele is not a lethal disorder, the neurologic sequelae are progressive, and worsen until the lesion is closed. Observational and cohort studies have demonstrated improvement of the Chiari II malformation (32,33), decreased hydrocephalus (34), and improved lower extremity function after intrauterine repair of myelomeningocele (35).

On the day of surgery, the pregnant patient is taken to a standard obstetrical operating room. An epidural catheter is placed and, after induction of general endotracheal anesthesia, she is prepared as if for a cesarean section. Many of the general anesthetic agents cross the placenta and provide analgesia for the fetus, and the epidural catheter enables the administration of continuous postoperative analgesics if needed. The gravid uterus is exposed with a Pfannenstiel incision and exteriorized. The uterine contents are then mapped with a sterile ultrasound transducer, and the location of the fetus and the placenta are determined. Initial uterine entry is obtained with a specialized trocar developed at Vanderbilt University Medical Center (Cook Incorporated; Bloomington, IN). The Tulipan–Bruner trocar consists of a tapered central introducer covered by a peel-away Teflon sheath. Use of this trocar has demonstrated to reduce operative time and blood loss while providing atraumatic entry into the uter-

ine cavity (36). Two through-and-through chromic sutures are passed through the uterine wall and membranes on either side of the selected entry point. The introducer is then passed into the uterine cavity under direct ultrasonographic guidance using a modified Seldinger technique. The central introducer is then removed, leaving only the trocar sheath. Excess amniotic fluid may be aspirated and stored in sterile, warm syringes. The footplate of a U.S. surgical CS-57 autostapling device (United States Surgical Corporation; Norwalk, CT) is then inserted through the peel-away sheath, and the sheath is removed, leaving the stapler in proper position. When activated, the stapler creates a 6–8 cm uterine incision. At the same time, all the layers of the uterine wall are held together, much like the binding of a book.

The fetus is directly visualized and manually positioned within the uterus so that the myelomeningocele sac is located in the center of the hysterotomy. Proper position is maintained by grasping the fetal head and trunk through the flaccid uterine wall. During the procedure, the fetal heart rate is monitored by continuous ultrasonographic visualization.

The myelomeningocele is closed in routine neurosurgical fashion. Approximately 20% of patients will not have a wellformed myelomeningocele sac, but a crater-like lesion termed myeloschisis. As fetuses with myeloschisis have less viable skin for closure, it may be necessary to use bilateral vertical relaxing incisions in the flanks to create bipedicular flaps that can be advanced and closed over the dural sac. The resulting full-thickness cutaneous defects are covered with cadaveric skin (37).

After repair of the spina bifida lesion, the uterus is closed in layers using #1 PDS sutures. The first layer incorporates the absorbable polyglycolic acid staples left by the autostapling device. As the last stitches of this layer are placed, the reserved amniotic fluid or physiologic crystalloid solution, mixed with 500 mg of nafcillin or an equivalent dosage of an antibiotic effective against Staphylococcus species, is replaced in the uterus. The sterile, warm fluid is added until the uterine turgor, as determined by manual palpation, is restored to the preoperative level, which is followed by an imbricating layer. A sheet of Interceed absorbable adhesion barrier (Johnson & Johnson Medical, Inc.; Arlington, TX) or omentum is attached over the incision to prevent adhesion formation. The uterus is returned to the abdomen. The fascial layer is closed in routine fashion, and the dermis closed with a running subcuticular suture or staples. The fetus is monitored postoperatively using continuous electronic fetal monitoring (EFM) and intermittent transabdominal ultrasonography.

Postoperative uterine contractions are monitored using continuous EFM. Uterine contractions are initially controlled with intravenous magnesium sulfate and oral or rectal indomethacin, and subsequently with subcutaneous terbutaline or oral nifedipine, supplemented by indomethacin as needed. Patients are monitored with weekly transabdominal ultrasonographic examinations. Delivery of each child is accomplished via standard cesarean section. Although the same abdominal incision is used for the cesarean section as for the fetal surgery, the fetus is preferably delivered via a lower uterine segment incision.

176 INTRAUTERINE SURGICAL TECHNIQUES

The uterus and abdominal incisions are closed in routine fashion.

VALVULOPLASTY

Severe aortic stenosis in midgestation may lead to left ventricular myocardial damage and can ultimately result in hypoplastic left heart syndrome. Paradoxically, in these fetuses, which are likely to progress to HLHS, the left ventricle initially appears normal in size, or even enlarged, in the setting of left ventricular systolic dysfunction. As gestation progresses, diminished flow through the diseased left ventricle leads to decreased flow, and the ventricle experiences growth arrest, resulting in left heart hypoplasia at birth. Early relief of fetal aortic stenosis may preserve left heart function and growth potential by maintaining flow through the developing chamber. To this end, a number of operators have developed techniques to perform fetal aortic valvuloplasty in second trimester fetuses.

The mother is placed under general anesthesia in a supine position with left lateral uterine displacement. Transabdominal ultrasound imaging and external manipulation are employed to achieve ideal fetal position. In this position, a line of approach from the anterior abdominal surface traverses the apex of the fetal left ventricle (LV), paralleling the LV outflow tract, and crossing the valve into the ascending aorta. The fetus is given intramuscular anesthetic and muscle relaxant prior to catheterization. If unable to position the fetus using external maneuvers, the operators perform a limited laparotomy to enable direct uterine manipulation and transuterine imaging.

A low profile, over-the-wire coronary angioplasty catheter is chosen with a balloon diameter based on the measurement of the aortic annulus, using a balloon:annulus ratio of 1:2. The balloon catheter is mounted on a floppytipped guidewire, with 3 cm of distal wire exposed. The wire/catheter assembly is then advanced through the 19G 12 cm stainless-steel introducer cannula until the balloon emerges. Affixing a visible and palpable marker on the proximal catheter shaft allows the operator to reproduce this balloon/cannula relationship during the procedure without relying wholly on the ultrasound imaging.

The introducer is advanced through the fetal chest wall and to the LV epicardium under ultrasound guidance. The LV is entered with the introducer, and the obturator removed with the tip of the cannula just below the aortic valve (Fig. 1). Blood return through the cannula confirms an intracavitary position.

The wire/catheter assembly is passed through the cannula, and the tip of the wire is identified as it emerges. While maintaining imaging of the aortic valve and ascending aorta, the precurved wire tip is manipulated to probe for the valve. Valve passage, confirmed echocardiographically by imaging the wire in the ascending aorta, is followed by catheter insertion to the premarked depth. The balloon is then inflated, by hand or by pressure gauge, to a pressure at which it achieves the intended balloon:annulus ratio. Upon completion of the dilation, the entire apparatus is removed from the fetus.

Figure 1. Transabdominal ultrasound imaging during introducer cannula insertion into dilated fetal left ventricle. The tip of the introducer is positioned in the left ventricular outflow tract directed at the stenotic aortic valve.

When first reported in the 1990s, fetal aortic valve dilation was performed with minimal technical success (38). Using the technique described above, technical success rates are now over 80% in fetuses between 21 and 26 weeks (39). As the technical aspects of the procedure continue to be refined, and safety is established, issues of patient selection will become the major focus of ongoing research. Anatomic and physiologic variables predicting left ventricular normalization following successful fetal aortic valvuloplasty remain poorly understood.

AMNIOEXCHANGE

Gastroschisis is a paraumbilical defect of the anterior abdominal wall associated with intrauterine evisceration of the fetal abdominal organs. The incidence of gastroschisis is approximately 1:4000 births, with a 1:1 male:female ratio. Most cases are sporadic and aneuploidy is uncommon.

Gastroschisis is characterized by a full-thickness defect of the abdominal wall, usually located to the right of the umbilical cord, which has a normal insertion. The defect in the abdominal wall is generally quite small (3–5 cm). The herniated organs include mainly bowel loops, although, in rare cases, the spleen and liver may be involved. Intestinal atresias and other gastrointestinal disruptions are found in as many as 15% of cases, and malrotation is also universal.

Although the prognosis is excellent with an ultimate survival of greater than 90%, many factors may jeopardize the outcome of these infants. A chronic aseptic amniotic fluid peritonitis (perivisceritis) often occurs. The herniated organs become covered by an inflammatory peel in the third trimester, resulting from chemical irritation by exposure to digestive enzymes in the amniotic fluid. Thickening, edema, and matting together of the intestines occurs in these cases, and may result in a secondary ischemic injury

to the bowel as the abdominal defect becomes too small. Meconium is frequently found in the amniotic fluid of affected fetuses. Its presence probably reflects intestinal irritation. Intrauterine growth restriction (IUGR) is frequent, occurring in up to 60% of fetuses. Oligohydramnios can occur, and may lead to fetal stress by cord compression. Premature birth is a frequent and still poorly understood complication. At birth, infants have low serum albumin and total protein levels, which probably results from chronic peritonitis.

The obstetrical management of the fetus with gastroschisis is controversial. Some studies have shown no clear benefit of cesarean delivery over vaginal delivery, where as others demonstrate an improved perinatal outcome in infants delivered by elective cesarean section prior to labor. Postoperative infection and delayed total enteral nutrition are the major acute complications of the newborn. Although all neonates with gastroschisis require surgery shortly after birth, repair may be by primary fascial closure, or by delayed fascial closure using temporary coverage with a silastic/Dacron intra-abdominal pouch. The repair as a primary or secondary procedure depends on the degree of chemical peritonitis with matting of the bowel that is present. Delayed intestinal function with poor enteral nutrition is expected in most patients. Central venous access and early total parenteral nutrition are therefore usually required.

In a study by Luton et al. (40), gastroschisis was created at mid gestation in 21 lamb fetuses. Saline was amnioinfused in some fetuses every 10 days until term. Thickness of the bowel muscularis, thickness of the serous fibrosis, and plasma cell infiltration were all significantly improved in amnioexchanged animals when compared with fetal lambs that were not amnioexchanged (40). Histologic analysis of appendices removed from human newborns demonstrated increased fibrosis in those with gastroschisis; after amnioinfusion, the serosa was still edematous, but no inflammation was seen (41). In a pilot study in human pregnancies (42), the same authors investigated the effect of amnioinfusion on the outcome of prenatally diagnosed gastroschisis. Following up on their work showing that an inflammatory response exists in the amniotic fluid of fetuses with gastroschisis, they hypothesized that amniotic fluid exchange would improve the outcomes of prenatally diagnosed cases. The outcome of 10 amnioinfused fetuses with gastroschisis was compared with 10 nonamnioinfused matched controls. Results showed that fetuses undergoing amnioinfusion had a shorter duration of curarization after

(49.7 21.5 versus 72.3 56.6 days, NS) and a shorter overall length of hospitalization (59.5 19.7 versus 88.5 73.6 days, NS). The authors confirmed their previous data showing that amniotic fluid displays a chronic inflammatory profile, and they speculated that a reduction of the inflammatory response could improve the outcome of human fetuses with gastroschisis (42).

Amnioexchange for treatment of gastroschisis begins after 30 weeks’ gestation, and is repeated approximately every two weeks until delivery. A complete obstetrical ultrasound examination is performed prior to the amnioex-

Figure 2. Views of the uterus.

change. The patient is admitted to the labor and delivery suite, and a nonstress test is performed before and after the amnioexchange. An intravenous line or a heplock is placed, and a single vial of blood is obtained and held for routine admission laboratory studies, in the case that urgent delivery is required. Prophylactic tocolysis may be given in the form of intravenous or subcutaneous terbutaline. Light IV sedation may also be given if desired.

After performing a sterile abdominal prep and drape, amnioexchange is performed using a ‘‘closed system.’’ The closed tubing system materials are illustrated in Fig. 2. All of the materials are sterile except the graduated cylinder. Two sterile three-way stopcocks (b and c) are connected end-to-end. Sterile IV solution (a) is connected to stopcock

(c) by way of sterile IV tubing (a). Three lengths of sterile connecting IV tubing (b) are connected to the remaining exposed ports of the stopcock assembly. Tubing from the side port of stopcock (b) is allowed to drain to the graduated cylinder (d). A 60 mL syringe (e) is connected to the tubing attached to the inline port of stopcock (b). The tubing attached to the inline port of stopcock (c) will connect to the therapeutic amniocentesis needle. Stopcock (c) is closed off to the IV solution (a). Stopcock (b) is closed off to the graduate (d). Amniocentesis is performed under continuous ultrasound guidance. Once access is obtained, the stylet is removed from within the needle lumen and the connection tubing is attached. With the stopcocks positioned as noted above, amniotic fluid is withdrawn into the syringe (e) until the syringe is filled. Stopcock (b) is then closed off to the patient and the fluid is expelled into the graduate (d). Stopcock (b) is then turned off to the graduate (d), and this step is repeated until the desired amount of amniotic fluid has been withdrawn (300–900 ml). With stopcock (b) closed to the graduate (d), stopcock

(c) is closed off to the patient. The syringe is then filled with sterile warmed saline. Stopcock (c) is then closed to the IV solution (a) and the fluid is infused into the patient. This step is repeated until the desired amount of fluid is infused. These steps are repeated serially until the infusion procedure is complete. If the amniotic fluid volume falls within normal range, the amniotic fluid volume at the end of the amnioexchange should be the same as at the beginning of the procedure. In the presence of oligohydramnios, additional sterile warmed fluid can be added to the uterine cavity in order to achieve a normal fluid volume by the end of the procedure.

178 INTRAUTERINE SURGICAL TECHNIQUES

If the fluid volume is normal, the placenta is located posteriorly or fundally, and the fetus is quiescent, all of the toxic amniotic fluid planned for removal might be aspirated in one step. With an anteriorly implanted placenta, however, or in the presence of oligohydramnios or an active fetus, it may be necessary to remove a small amount of amniotic fluid, and then replace it with warmed normal saline, repeating the procedure serially until the amnioexchange is completed.

After completion of the amnioexchange, electronic monitoring of the fetal heart rate and uterine activity continues until the patient fulfills the usual criteria for discharge.

AMNIOPATCH

Iatrogenic preterm premature rupture of membranes (PPROM) occurs in approximately 1.2% of patients after genetic amniocentesis (43), 3–5% of patients after diagnostic fetoscopy (44), and approximately 5–8% of patients after operative fetoscopy. Although the membranes might seal spontaneously in this setting (45,46), most patients continue to leak fluid and are at a risk for pregnancy loss.

The overall perinatal mortality of previable PPROM managed expectantly is 60% (47,48). Nearly one-third of these deaths occurs in utero. Pulmonary hypoplasia occurs in 50% of cases diagnosed before 19 weeks (49). Serious sequelae in surviving infants include blindness, chronic lung disease, and cerebral palsy.

Patients with iatrogenic PPROM between 16 and 24 weeks gestation who do not have clinical evidence of intraamniotic infection are candidates for amniopatch therapy. PPROM is confirmed with a sterile speculum examination showing vaginal pooling of fluid, ferning, and a positive Nitrazine test. The maximum vertical pocket of amniotic fluid is measured sonographically. Patients are placed on intravenous antibiotics and bed rest for one week to allow for spontaneous sealing of the membranes. If spontaneous sealing does not occur, 1 unit of autologous platelets and cryoprecipitate are prepared if the patient is eligible for autologous donation. Otherwise, donor platelets and cryoprecipitate are prepared.

After informed consent, an amniocentesis is performed using a 22 gauge needle. The needle is directed into an available pocket of fluid regardless of the site of the previous invasive procedure. A K-51 tubing extension attached to a three-way stopcock is connected to the hub of the needle. Platelets are administered first, followed by cryoprecipitate. In our original protocol, 1 whole unit of platelets was injected. We have subsequently reduced the dose of platelets to one-half a unit because of an unexplained fetal death demise, an adverse effect probably caused by sudden activation of a large number of platelets.

In our series of 28 cases, the average gestational age at the time of the procedure was 19 weeks and 3 days. The average gestational age of delivery in patients who did not have an intrauterine fetal demise was 33 weeks and 4 days. Overall, membrane sealing occurred in 19 of 28 patients (67.9%). Of the 28 patients treated, 11 had a large membrane detachment but no overt leakage of fluid. The detachment of the membrane occurred from fluid escaping

the amniotic cavities through the membrane defect, causing dissection of the chorionic cavity. In these patients, only the chorion separates this fluid from leaking grossly to the vagina. In this group, the amniopatch was successful in resealing the amniotic membrane in 7 of the 11 patients (63.6%).

The precise mechanism by which the amniopatch works is unknown. Presumably, platelet activation at the site of rupture and fibrin formation initiates a healing process that enables the membranes to seal.

TTTS

Feto-fetal transfusion syndrome can be described in all monochorionic multiple pregnancies but has been extensively reported in twins. Twin-to-twin transfusion syndrome (TTTS) develops in approximately 15% of all monochorionic pregnancies (50), and carries a high perinatal mortality rate (50). The fetuses are morphologically normal, and inter-twin vascular communications on the chorionic plate are thought to be responsible for the development of the disease through unidirectional blood transfusion from the donor to the recipient twin. Besides the primary hemodynamic imbalance between the twins, the disease may lead to disruptive lesions in both twins. Before the development of antenatal ultrasound, TTTS was diagnosed at birth as a discordance of at least 20% in weight and 5 g/dL in the hemoglobin concentrations of two twins of the same sex (52). These criteria were abandoned because these features could not be consistently recognized in utero. With the development of ultrasound, the polyhydramnios-oligohydramnios sequence has been found to be the condition carrying one of the highest perinatal mortality rates in obstetrics, up to 90% without treatment.

Laser coagulation of placental anastomoses by fetoscopy is the most effective first-line treatment of FFTS, which leads to at least one survivor at birth and intact survival at 6 months of age in 76% and 76% respectively, as compared with 56% and 51% in cases treated by serial amnioreduction in the Eurofetus randomized trial (53).

The selection criteria to qualify for percutaneous endo- scopy-directed laser coagulation of placental anastomoses include:

1.Gestational age of less than 26 weeks.

2.Ultrasound diagnosis of a single monochorionic placenta by ultrasound in the first trimester of pregnancy.

3.Polyhydramnios in the recipient’s amniotic cavity with a deepest vertical pool 8 cm or 10 cm before or after 20 weeks of gestation, respectively.

4.Oligohydramnios in the donor’s amniotic sac with a deepest vertical pool 2 cm.

Preoperative evaluation consists of ultrasound examination, including morphological examination, fetal Doppler, cardiothoracic index, identification of placental location, and cord insertions. Amniocentesis or amniore-

duction prior to laser may cause intra-amniotic bleeding and therefore make the procedure more difficult, or even impossible, due to impaired visualization. The site of entry is chosen as demonstrated in Fig. 1, for the scope to be entered at a right angle to the long axis of the small twin in order to maximize the chance to ensure adequate visualization of the placental surface and intertwin membranes. Ideally, the scope should also be entered alongside a virtual line joining the two cord insertions. When these criteria are met, the vascular equator of the placenta as well as the vascular anastomoses on the chorionic plate are more likely to be visualized in the operative field.

Prophylactic cefazolin 2 g, indomethacin suppository 100 mg, and oral flunitrazepam are given before surgery and local anesthesia with nonadrenalinized xylocaine is injected down to the myometrium. A 10 Fr cannula for a central venous catheter loaded with a trocar is introduced percutaneously under continuous ultrasound guidance. A 2 mm 08 fetoscope (Storz 26008 AA) is passed down a straight or curved sheath to operate on posterior or anterior placentas, respectively. The sheath also has a working channel carrying a 1 mm diode laser fiber.

A systematic examination of the chorionic plate alongside the insertion of the inter-twin membrane is performed. Identification of crossing vessels and of their arterial or venous nature is possible because arteries cross over veins and show a darker red color than veins owing to a lower oxygen saturation in the circulating blood (54). Selective coagulation of anastomotic vessels is performed with the aim of separating the monochorionic placenta into two distinct fetal-placental circulations, sparing the normal cotyledons of each placental territory. Nonselective coagulation of crossing vessels is only performed when the distal end or the origin of the vessel cannot be identified. The power of the diode laser is set at 30–50 w. At the end of theprocedure, excessive amniotic fluid is drained through the sheath of the fetoscope until normal amniotic fluid volume is obtained with a deepest vertical pool of 5–6 cm.

BIPOLAR UMBILICAL CORD OCCLUSION

Selective reduction in complicated monochorionic (MC) multifetal pregnancies is performed to prevent the delivery of an anomalous or severely compromised fetus and improve the perinatal outcome for the surviving co-twin by delaying delivery or risk associated with spontaneous loss of the affected. The use of cardiotoxic agents, such as potassium chloride, is contraindicated in MC pregnancies because of the potential vascular transmission of the agent and compromise of the co-twin due to the presence of placental vascular anastomoses. Thermal vascular occlusive techniques, such as bipolar umbilical cord occlusion (BPC), have been shown to achieve the stated goals with minimal maternal morbidity. Indications for BPC that are unique to MC gestations include twin reverse arterial perfusion, discordant fetal anomalies, and isolated severe growth lag. BPC has also been used as a primary intervention in advanced twin-twin transfusion syndrome or as a secondary procedure when alternative therapies such as

amnioreduction or laser have failed to correct the disease process.

The procedure was originally described by Deprest et al. (55). In brief, using the standard sterile technique, the patient’s abdomen is properly prepared and draped. An abdominal ultrasound is performed to confirm fetal position, viability, and umbilical cord locations. General and conduction anesthesia may be used; however, intravenous sedation with local infiltration of 1% lidocaine or 0.25% bupivicane for subcutaneous, deep muscle, and fascia anesthesia is usually sufficient and is associated with less maternal morbidity. A small skin incision is made to allow insertion of an endoscopic trocar. Under continuous ultrasound guidance, the instrument is inserted through a placental free window toward the targeted umbilical cord, ideally avoiding the gestational sac of the normal co-twin. Once the trocar is secured in the amniotic sac, the obturator is removed. The bipolar forceps are inserted and advanced to the umbilical cord.

The cord is grasped and positioned away from the amnion before thermal energy is applied. The duration and wattage (W) necessary for occlusion will vary, from 20–60 s and 20–50 W, respectively, based on the gestational age and umbilical cord thickness. When a full-thick- nessgrasp exists, application of the thermal energy will result in turbulence and ‘‘streaming’’ of amniotic fluid adjacent to the forceps. It is not uncommon to have an audible ‘‘pop’’ secondary to the heating of Wharton’s jelly and subsequent rupture of amnion at the site of occlusion, which should not be perceived as a sign of completed coagulation. As a result of the natural spiral of the umbilical cord, complete occlusion of all vessels requires 2–3 applications of the forceps at adjacent sites. Pulse and color flow Doppler blood flow studies are performed to confirm cord occlusion at each site.

The size of the BPC forceps that have been used for these procedures has varied from 2.2–5.0 mm. The majority of procedures have been performed with commercially available single-use 3.0 mm bipolar diathermy forceps (55–58).

Intravenous prophylactic antibiotics and indomethacin for tocolysis are generally given prior to the procedure. Postoperative monitoring for uterine contractions and, depending on the gestational age, continuous or intermittent fetal heart rate should be done for at least 2 hours. The majority of programs will observe patients for an extended period of 12–24 h with limited activity. Subsequent doses of antibiotics and tocolytic treatment are given during this time. Prior to discharge, a limited ultrasound is performed to determine the amniotic fluid volume and assess for signs of hydrops and anemia, including Doppler velocemitry of the middle cerebral artery and, where appropriate, similar studies of the umbilical artery and ductus venosus. If no evidence of preterm labor, leaking of amniotic fluid, or bleeding exists, the patient is discharged with instructions to continue with modified bed rest at home for 7–10 days, take her temperature bid, and report an elevation, leaking of vaginal fluid, bleeding, or contractions. An ultrasound is performed in 10–14 days and then at a minimum every 4 weeks thereafter. Additional ultrasounds and fetal monitoring should be performed as clinically indicated by the primary disease and gestational age.

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