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Monozygotic, monochorionic, and isosexual twins united by a part of their anatomy are known as Conjoined Twins. This is a rare and fascinating malformation that represents one of the more complex challenges of pediatric surgery. The twins are classified into two main groups: asymmetric and symmetric. Asymmetric ones are acardius acephalus, fetus-in-fetu, or heteropagus twins. In all these, only one component, the autositus supplying circulation, is viable. Symmetric twins are designated craniopagus, thoracopagus, omphalopagus, rachiopagus, ischiopagus, pygopagus, or parapagus according to the location of the joining bridge. This can be large and often contains shared organs. The cardiovascular systems of both components of the set are communicated and the internal environment is also shared to a variable extent.
Mortality is high before and after birth because of frequent and severe associated malformations. Viability of separation is difficult to determine and requires sophisticated imaging studies. Separation not only involves lengthy and complex operations but also difficult ethical decisions with familial, medical, and even court participation.
Separation, when possible, requires various groups of specialists under a strong leadership. Bony parts, nervous system, hearts, great vessels, digestive and genitourinary organs, as well as the skin and musculoskeletal tissues have to be divided and reconstructed to achieve separation with preservation for each component of as much function as possible. Survival is nearly impossible when the hearts are united, but it is possible for one or both twins in all the other forms. Complications are frequent and long-term quality of life is often burdened by fecal and urinary incontinence or by abnormal limbs and genitalia that are the price to pay for separation.
The quality of a pediatric surgical group is heavily put to test by these cases that can only be managed when outstanding expertise is available in the various specialties involved.
KeywordsConjoined Twin Acardius Acephalus Heteropagus Parasitic Craniopagus Thoracopagus Omphalopagus Ischiopagus Pygopagus Parapagus Separation Ethics
Conjoined twins are physically fused at birth. They share a single chorion, placenta, and amniotic sac (Arnold et al. 2018). Genetically identical individuals joined by a part of their anatomy and often sharing one or more organs are known as “conjoined twins.” This event occurs in 1:50,000 to 1:100,000 live births (Mutchinick et al. 2011), and it involves complex anomalies and technical and ethical issues that represent one of the hardest challenges of pediatric surgery.
This obvious condition that may involve dramatic obstetric issues was known from ancient times. Probably two-faced deities like Jano or multiple-headed creatures like Hydra were introduced into mythology after observation of such twins. There are pictures and carvings depicting conjoined twins in cultures from various continents. Conjoined twinning raised moral dilemmas and risky definitions (for instance, how many souls they have?). One of the first descriptions of esophageal atresia was based on the autopsy of a set of conjoined twins but they only became popular after certain sets were exhibited as freaks or circus attractions. This was the case of Chang and Eng Bunker, the original Siamese twins, who were taken for this purpose from Siam to the USA, where they eventually settled and lived for more than 50 years. Many examples have been publicized ever since and they are often addressed in the media.
Due to the complexity of the technical problems involved, it is understandable for the first separations to be relatively recent (17th century) (van der Weiden 2004). However, many unsuccessful separations were never reported and the high mortality of this condition is still largely hidden.
The current etiology of conjoined twins is still not fully understood. There are two theories for the pathogenesis of conjoined twins. The first one asserts that incomplete fission of the early embryo produces identical twins that shared anatomic structures (Spitz and Kiely 2003; Arnold et al. 2018). Monozygostic twins occur when an embryo divides before day 13. An embryo that divides on or after day 13 will not divide completely and will remain with fused organs of various degrees, producing conjoined twins. The extent of division and subsequent development will determine the degree of shared anatomy between the twins. The second theory states that conjoined twins are the result of secondary fusion of embryos from a completely separated fertilized egg (Arnold et al. 2018; Kobylarz 2014; Spencer 1996). The twins are always joined by central parts of their anatomies and they are always homologous in the sense that they never have the head or the lower limbs on opposite sides. This is consistent with the previously mentioned interpretation of the embryonic mechanism.
Some experiments in amphibians and a few modern molecular genetic observations suggest that fusion of two originally separated embryos may be the explanation for some rare cases in which there is sex discordance (Logrono et al. 1997; Martinez-Frias 2009).
The location, extent, and nature of the bridge that joins both twins vary widely and this complicates description of the anatomy of each individual set (Pierro et al. 2015). Several classifications attempted at simplifying description. Conjoined twins were divided into ventrally and dorsally joined and subdivided according to the level of fusion (Spencer 2003). It is probably simpler to divide them according to their asymmetric or symmetric nature and to the level of the fusion that is followed by the suffix pagus.
Asymmetric twins include “fetus in fetu,” acardius acephalus, and heteropagus parasitic twins. The adscription of the first variety of organoid teratomata to the family of conjoined twins is only acceptable when they are “organoid” and contain a more or less rudimentary spine (Spencer 2001). Acardius acephalus is a variety of parasitic twin devoid of heart and head that is connected by marginal placental vessels with the healthy twin (the autositus) that accounts for circulation and nutrition of both. Heteropagus twins are usually attached to the abdominal wall of an anatomically normal autositus twin, without or with exomphalos, and appear as organoid parasitic masses containing various organs and limbs unable to sustain independent circulation by themselves (Bhansali et al. 2005; Abubakar et al. 2011).
Symmetric conjoined twins are classified according to the body parts that are fused: cephalopagus (11%, head to umbilicus), thoracopagus (19%, thorax to umbilicus), omphalopagus (18%, umbilicus), ishiopagus (11%, lower abdomen and pelvis), paragagus (28%, lower abdomen and pelvis), craniopagus (5%, cranium, but not foramen magnum/skull based), rachipagus (2%, vertebral column), and pygopagus (6%, sacrum and perineum) (Arnold et al. 2018; Baken et al. 2013).
Nowadays, most conjoined twins are prenatally diagnosed by ultrasound and this allows prevention of potentially serious problems during vaginal delivery. Except in the thoracopagus twins with common heart and in the asymmetric twins, both fetal heart tones can be heard like in regular twins. The heads and the limbs of conjoined twins are on the same side (this is why they are termed “homologous”) in contrast with regular twins that are usually arranged in opposite directions. This allows fetal ultrasonographic (US) diagnosis that leads to more sophisticated US and/or magnetic resonance imaging (MRI) studies aimed at defining the anatomy of the fusion and the chances of separation (Andrews et al. 2006; Lopes et al. 2013). Associated anomalies that can be diagnosed readily in expert hands (Brizot et al. 2011) are more frequent in regular twins than in singletons and this is more so in conjoined ones. Since they may condition viability of the twins, their detection sometimes prompts termination of pregnancy.
Serious malformations or trauma suffered by only one of the twins may create difficult clinical situations because crossed circulation creates a single internal environment which is hard to manipulate: the healthier twin can compensate in part for the problems of the diseased one, but the latter may expose the former to disbalances, toxins, or medications (Lai et al. 1997).
The diagnosis remains easy, even if some of the associated congenital abnormalities cannot be seen at the early gestational stage. A comprehensive understanding of the anatomy of the organs and the distribution of their functions is necessary for planning viable separation strategies. Plain X-rays, gastrointestinal (g.i.), or urogenital (g.u.) tract contrast studies may depict the points of junction and other features of the corresponding organs but, due to the atypical anatomy (Kingston et al. 2001), incomplete understanding leads to unexpected surprises. Ultrasonographic (US) study helps at every diagnostic step (Andrews et al. 2006). Ultrasound enables an early and accurate diagnosis of conjoined twins. The first trimester ultrasound is the best method for diagnosing conjoined twins in early pregnancy (Mathew et al. 2017; Melo et al. 2018). Angiography, widely used in the past for imaging the nature of the blood supply in the shared organs, is currently replaced by computerized tomography (CT) or magnetic resonance angiography (angio-MRI) (McHugh et al. 2006). CT angiography is the best way for depicting the vascular arrangement (Ohashi et al. 2012; Tannuri et al. 2013). MRI is an excellent imaging modality for tissue characterization and better depicts the fused neural and meningeal tissues in craniopagus, rachiopagus, ischiopagus, pygopagus, or parapagus. Both CT and MRI are crucial for imaging the anatomy of conjoined hearts. Helical CT reconstruction of the bony junctions may help in preparing strategies of skeletal separation (Martinez et al. 2003) (Figs. 4 and 5). Nuclear imaging may help to define the functional anatomy of the liver, kidney, or other organs (Rubini et al. 1995; Chen et al. 2011). However, unexpected anatomical surprises that may change the order or the nature of the participation of the different specialists involved are frequent. In most cases, the expected anatomy does not fully fit the surgical findings and some ingenuity is required for improvising solutions.
Hematologic and biochemical studies are often misleading due to the situation of crossed circulation. When the vascular channels are large, parabiosis is complete, but when only minor territories are in connection, both twins maintain some internal environmental differences that can be relevant in cases in which blood tests are necessary for diagnosis. Other tests, like ECG, are challenging when the hearts are connected (Carton et al. 2011). Metabolic rate may show considerable differences between twins upon calorimetry (Powis et al. 1999).
Preoperative Ethical Issues
The principles that regulate the practice of medical profession are particularly difficult to respect in conjoined twins and serious ethical dilemmas are to be expected (Atkinson 2004; Lee et al. 2011; Spitz 2015):
The principle of autonomy (the decisions taken by the patient after honest and complete information should be respected) cannot be fully applied in children for obvious reasons and has to be exerted by proxy by the parents. This may be a source of conflicts among them (for instance, one may want a separation to be attempted and the other one may refuse it) or with doctors or the courts. Any effort to reach unanimous decisions agreed upon after informed consent should be made (Boudreaux and Tilden 2002).
The principle of justice (similar chances for both patients) is obviously at risk when it comes to separation that may involve mutilation or sharing of organs. Choices should be made taking into account that distribution of organs and tissues has to be fair for both members of the set. All possible actions should attempt at complying with this principle although the limitations are obvious.
The principles of beneficiency and non-maleficiency (the benefit of the patients should be sought and no harm should be inflicted to them), that are considered as the ethical backbone of medical decision-making process, are also difficult to apply if separation is necessary for the survival of only one twin, if distribution of organs is uneven, and if separation involves, as it is usually the case, loss of some functions that might be preserved without separation.
When separation of conjoined twins is considered, the patients are usually too young for deciding by themselves, the parents are heavily influenced by information delivered by doctors, and the team involved is usually so large and often ethically discordant that keeping a unified line of decision becomes difficult. Acknowledgement of a strong moral leadership after open discussion of every issue is required before providing information about the chances and the consequences of separation to the caretakers. In case of serious discrepancies among all participants in the process of decision, the courts might be involved (Gillon 2001).
Furthermore, the media (whose interference is difficult to avoid due to the large amount of people involved) almost constantly creates new difficulties. The twins and their family have to be protected from these agents and, if possible, the entire process of decision-making and even the separation should be kept in the shade. Unfortunately, this is difficult to put into effect. Too many people are involved in the treatment of conjoined twins while being mesmerized by them. Corruption by the media can easily put unauthorized pictures and films in circulation and sometimes, the families themselves cast information in exchange of economic support. All these actions may be damaging for the twins and should be prevented whenever possible.
When separation has been decided, one or more meetings with scrub nurses, nurses, anesthesiologists, and surgeons of the specialties involved (general pediatric, orthopedic, plastic, urologic, neurologic and cardiovascular surgery) should be scheduled (Al Rabeeah 2006). Technical aspects should be discussed, and the operation itself should be rehearsed because installation of the set of twins on the table, skin prep and draping, as well as transport of one twin with the corresponding anesthetic equipment to another table for reconstruction after separation should be carried out according to a previously established plan (Kiely and Spitz 2015). The expected order and extent of the participation of each specialist team in the separation should be scheduled as well. The surgeon in charge of the direction of the operation acts as an orchestral conductor and his/her coordinating activity extends well beyond the end of the separation itself.
Recent advances, such as 3D printing, may aid in surgical pre-planning, thereby enabling successful surgical separation of conjoined twins (Mathew et al. 2017).
Anesthesia is a serious challenge not only because of the obvious anatomical difficulties for intubation, insertion of lines, and invasive monitoring but mainly because of the previously mentioned situation of parabiosis in which one single internal environment is shared to variable extents by the twins. The drugs administered to one pass on into the other one and biochemical and gas monitoring may be confusing (Thomas and Lopez 2004; Szmuk et al. 2006). In difficult cases, it may be worth to proceed with preanesthetic manipulations and line insertions one day before the operation itself in order to leave time enough for this.
Asymmetric conjoined twins represent in general surgical challenges that are not unlike other ones met in this specialty. The Acardius acephalus parasitic twin is inviable and dies upon clamping the umbilical cord of the host (autositus). Intrauterine occlusion of the umbilical cord of the parasitus allows termination in cases in which cardiac failure of the autositus threatens survival. It should be pointed out that a considerable proportion of host fetuses have severe cardiac problems at birth as a result to adaptation of the new hemodynamic situation after separation. The Fetus in fetu is treated as a tumor. In fact, it is a teratoma with organoid tissues and a more or less rudimentary spine. Depending on size and location, the operation may be variably hazardous. Most cases are central or paraspinal and they may have close relationship with large vessels. Heteropagus asymmetric parasitic twins are removed with attention at preserving as much tissue of the host as possible in order to respect the organs and allow for wall reconstruction. Survival of the parasitus devoid of heart and brain is impossible and this allows for a large use of its tissues. After excision of the membrane of the exomphalos, the abdominal wall can be reconstructed with aponeurotic and/or muscle flaps using skin of the parasitus for coverage. Sometimes, bony parts of this have to be removed. In cases in which wall closure is impossible with autologous tissues, synthetic grafts can be used as in symmetric forms of conjoined twinning.
Separation of Craniopagus may be extremely difficult or even impossible given the complexity of the neural, arterial, and venous connections involved. Modern imaging and sophisticated neurophysiologic monitoring are particularly useful in these cases. The final amount and nature of the brain tissue and the vascular network shared by the twins set the limits for separation that may involve several stages (Browd et al. 2008; Staffenberg and Goodrich 2012). Serious difficulties are to be expected for separation, particularly venous and neurologic deficits, determined by the location and size of the brain junction, are very likely even after successful operations.
Separation of Omphalopagus twins involves variable difficulties depending on the extent of organ sharing. These twins have more often fused livers and g.i. tracts. It is customary to start separation by the liver, where more difficulties are to be expected. A small liver bridge without major vascular connections is relatively easy to take down but a large mass of anatomically atypical liver with wide arterial, venous, and biliary connections (Meyers and Matlak 2002) may be a formidable undertaking. Perioperative ultrasonography and parenchyma dividing devices used for liver resection (ultrasonic or water jet knives) are very useful for this purpose. The surgeons should ensure that adequate arterial and portal inflows, hepatic veins outflow, and patent biliary tracts are preserved in each half of the liver mass. Anatomic orientation may be difficult and all precautions are justified. In a number of cases, a large arterial trunk joins the abdominal aortas of both twins and temporary clamping is advisable before division. The raw liver surface is treated like in any other major liver resection. Careful ligation of the vascular and biliary radicals and coverage with fibrin adhesive in some cases will limit complications. As far as the gastrointestinal tract is concerned, the most common form of connection involves fusion of the small bowel from the upper jejunum down and divergence near the distal ileum. Separation consists in most cases of allocating half the available gut to each twin. Additional problems may be met when atresia of one of the tracts or a common cystic dilatation of the mid bowel are present. Regular techniques used in digestive neonatal surgery are also indicated in these cases (Cywes et al. 1997; el-Gohary 1998; Spitz and Kiely 2003; Rode et al. 2006).
Thoracopagus twins without connected hearts are separable in contrast with those with common myocardium (Thomas Collins et al. 2012). Only a few of them are amenable to surgery under cardiopulmonary bypass. Except in very rare cases in which narrow atrial or ventricular bridges exist, the only chance of separation involves using the bulk of myocardial material for one of the twins. Even if separation is attempted, the conduction system is heterotopic, and severe arrhythmias can intervene during surgery. In addition, these twins often have cardiovascular defects that may further complicate or preclude separation (Lopes et al. 2013). The aorta and the pulmonary arteries may be hypoplastic and, as described above, there may be communications between the infra-diaphragmatic aortas. In the very few cases successfully separated, only one twin survives and the tissues of the other one, including the sternum and/or ribs, can be used for bridging the large defect created in the thoracic wall during separation. Of those twins that cannot be separated, most die of the associated heart defects in the first months or years of life.
Rachiopagus, Ischiopagus, Pygopagus, and Parapagus twins share to different extent parts of the spine, central nervous system, gastrointestinal, and genitourinary tracts and they may represent formidable challenges. The separation of the bony parts requires highly skilled orthopedic surgeons. Careful design of the operation is necessary because osteotomies or synthesis of osseous tissue should aim at reconstructing the pelvis or the limbs, and this may require planned coverage with the available tissue. In some cases, the reconstruction of the pelvic rim requires bilateral iliac osteotomies and pubic fixation (Fig. 4). In other cases, even refashioning a bony pelvis is impossible and the subsequent prosthetic treatment is difficult (Kim et al. 2002; Fieggen et al. 2004) (Fig. 5). When the twins are united side by side, splitting the sacrum is necessary. Sometimes, this is better performed in two operative steps: one at the time of insertion of skin expanders and the other one during separation itself. The spine has often malformations at other levels, including asymmetric vertebra, anomalies in number, or malposition, and scoliosis has to be taken into account during follow-up.
Neurosurgical separation may involve dividing a common brain tissue or a spinal cord. In both cases reconstruction of the dura or dural sacs on each side directly or using biological prostheses is necessary (Fieggen et al. 2004). The motor and sensitive effects of separation of nervous tissue are variable depending on the location and extent of the fused tissue. Fused spinal cords (end-to-end in pygopagus and side-to-side in parapagus) are usually quite distal and separations have limited neurological effects. The neurosurgical part of some separations is particularly delicate because of the contaminated environment that is unavoidable when the gastrointestinal or genitourinary tracts have to be divided and particularly when enterostomies are established and when prosthesis are used for bridging dural defects.
Sharing the common lower g.i. tract between both twins entails the loss of continence for one or both of them. In twins joined by the lower abdomen or pelvis, there is often a single colon. The functional reconstruction of the colorectal area is therefore rarely possible. Rectal function can be seldom preserved in one twin but more often this is impossible in both and enterostomies have to be fashioned at some stage. Even if reconstruction of the anus and rectum are feasible, patients will only have half the colon or less and achieving reasonable continence is often impossible. All refinements of advanced bowel management (diet, enemas, antegrade wash-outs through a continent apendiceal stoma or a cecal button) are necessary to obtain subsequent adaptation of these patients to a more or less normal social life (Kim et al. 2002).
The same can be said about distributing the urogenital tract structures between the twins. Keeping a bladder and urethra for one of them is rarely possible in most frontally united sets. Again, all refinements of reconstructive urology, bladder augmentation, clean intermittent catheterization, and continent urinary diversion may help to readapt these patients (Holcomb et al. 1989; McLorie et al. 1997; Lazarus et al. 2011). The native genital tract can be reconstructed if duplicated but sometimes vaginal replacement is necessary (Kim et al. 2002).
One of the major technical problems posed by separation of conjoined twins is the coverage of the huge parietal defects left. When only one survives, part of the wall of the other one can be used to bridge the defects but in other cases, additional procedures are necessary. Several types of muscle and/or fascial flaps have to be fashioned, and in a number of cases, only the use of biologic or synthetic prostheses allows closing the gaps. When planning the separation, the availability of skin and subcutaneous tissue necessary for the type of closure elected should be estimated. Skin expansion with subcutaneous inflatable silicone expanders is often useful prior to separation. However, the same limitations mentioned for neurosurgical or bone procedures apply for expanders since the risk of bacterial colonization and infection with loss of the expansion is considerable when the operative field is contaminated by opening the gastrointestinal tract or simply by enterostomies.
The nature of these risky operations involves a large number and variety of possible complications. Intraoperative hemorrhage and damage to vital structures is always possible due to the atypical anatomy. Bone division or meningeal membrane opening simultaneous to gastrointestinal or the genitourinary procedures increase the risk of serious infection. Wound closure avoiding compartment syndrome may necessitate synthetic materials that are also exposed to contamination. Wound disruption and infection are therefore not rare. Finally, a wide range of complications not unlikely those seen after other major operations may occur: internal hemorrhage, abscesses, vascular thromboses, or postoperative intussusceptions, among others, are possible.
Early and Long Term Results
Overall mortality in conjoined twinning is high. When diagnosis is made during early pregnancy, interruption of gestation is common practice in developed countries particularly for the forms with poor prognosis (Martinez-Frias et al. 2009; Brizot et al. 2011). Fetal mortality or stillbirths are also frequent. Obstetric mortality or severe birth trauma remain a real risk when prenatal diagnosis was missed, and this happens more often in undeveloped countries in which pregnancies are not monitored. A considerable proportion of twins have multiple malformations that cause demise in the first hours or days of life (Kaufman 2004). When separation is deemed possible, it must be reminded that neonatal separations involve higher mortality mainly because they are only indicated for life-threatening reasons (for instance, one twin may be very ill or develop intestinal obstruction) but also because these complex operations are better performed when most anatomical and functional features of the set have been ascertained.
Thoracopagus twins with a common heart rarely survive because most have severe malformations. Of those sets in which separation is attempted, only a few individual twins survive (Chiu et al. 1994; Fishman et al. 2002). However, thoracopagus without shared heart can be successfully separated.
Most omphalopagus twins can be separated and survive if no obstetric trauma or severe associated malformation are present (Fig. 1). In all other forms of conjoined twinning a high proportion of the twins can be separated and survive although with more or less extensive deficits that require follow-up for life and often additional operations.
In the long term, separation of conjoined twins rarely produces independent individuals without sequelae. Some cases of asymmetrical twins and omphalopagi may survive separation and face a normal life. Most other cases keep orthopedic or neurologic sequelae or have fecal and urinary continence problems that become predominant with the passage of time. Orthopedic and motor deficits may require prolonged rehabilitation and/or prosthetic appliances. Permanent enterostomies are not rare and the most sophisticated procedures for obtaining urinary continence or dryness are necessary (Votteler and Lipsky 2005).
It is particularly discouraging that these pregnancies are often terminated in advanced medical and social environments able to provide lifelong assistance for rehabilitation and social integration whereas twins from less privileged countries that are diagnosed at term and eventually separated lack all the necessary facilities, all along their lives.
Conclusion and Future Directions
The intrinsic difficulties of separation of conjoined twins and the predictable deficits that will impair the quality of lives of survivors makes termination of pregnancy a widespread decision after prenatal diagnosis. Interestingly, this happens in developed countries where the health care systems and the social assistance institutions would allow the best integration of survivors. The majority of conjoined twins are born in less developed countries where often the expertise for separation and the framework of social assistance are lacking. These patients are often sent to the more experienced institutions, but it is difficult to offer them the life-long care that they require.
By any respect, conjoined twinning represents a major test for the quality of pediatric surgical care. Only institutions offering highly sophisticated pediatric surgical specialties can undertake these operations with a reasonable chance of success. It is therefore desirable to concentrate conjoined twins in only a few of them.
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