A model for fetal cleft lip repair in lambs.

Fetal wounds heal without inflammation and scar formation. This phenomenon may, in the future, be applicable to human cleft lip and palate repair. However, extensive experimental work must first be done to document the benefits of in utero repair. We developed a large animal model for creation and repair of a complete cleft lip and alveolus using fetal lambs. The cleft lip and alveolus deformity was created in eight 75-day-gestation fetuses (term = 145 days) and either repaired in three layers or left unrepaired. There were four sham-operated fetuses, and all animals were alive at harvest. Repaired, unrepaired, and control fetuses were harvested at 7, 14, 21, and 70 days following surgery. The unrepaired fetuses demonstrated a complete cleft lip and alveolus with an oronasal fistula. The maxilla was asymmetrical, with the greater segment deviated toward the cleft and with decreased anterior maxillary width. In contrast, repaired cleft lip and alveolus animals showed no scar, normal thickness of the lip, and a symmetrical maxilla. Histologic analysis of the repaired wounds showed evidence of tissue regeneration without scar formation. The results of this preliminary study indicate that the fetal lamb cleft lip and alveolus model is technically feasible with an excellent survival rate. Healing occurs without scar formation. In the repaired animals, the maxilla was symmetrical. This model will be used to document facial growth following in utero repair of a cleft lip and alveolus.     

In utero cleft lip repair in the mouse without an incision

In utero cleft lip repairs were done by full-thickness approximation of the cleft edges by 11-0 sutures in the A/J mouse on day 17 of gestation after Dilantin was administered on day 10. On day 20, a cesarean section was performed, the repair inspected, and the lip sectioned for histologic study. One-thousand one-hundred and thirty-nine mice were bred, and surgery was performed on 48. At least one fetus was present that had a cleft lip in 21 mice, and repairs were done on 16 fetuses. Ultimately, 9 viable fetuses were studied. In all cases, lip continuity was present where the suture had coapted the edges. There was little or no evidence of the lip repair despite no incision being performed. Histologic examination revealed epithelial and mesenchymal continuity with an occasional notch noted in the epithelium and soft-tissue asymmetry in complete clefts. The implications of these findings are discussed.     

A comparative analysis of healing of surgical cleft lip corrected in utero and neonates.

We studied the healing process in surgically created cleft lips in fetal mice and compared it with that in newborn mice with cleft lips. Our purpose was to determine the time for optimal healing, defined as minimal scarring, for a repaired cleft lip. Full-thickness paramedian lip incisions were made in NMRI mice in utero, in 2- and 4-day-old neonates, and in adults (n = 10 in each experimental and control group). The healing process was studied by biochemical analysis of hyaluronic acid and hydroxyproline content in the repaired cleft tissue. We found that the production of hyaluronic acid remained stable during the healing period and was similar in all experimental groups. However, there was an unexplained but consistent depression in the hyaluronic acid content of fetal tissue 2 days after repair. Hydroxyproline was present in the fetal healing tissue, but in a low concentration, starting 4 days after surgical incision of the lip. The production of hydroxyproline in 2-day-old neonates was similar to that in the fetuses throughout the healing period (p less than 0.0005). However, the production of hydroxyproline increased in 4-day-old neonatal and adult tissues. In conclusion, we found an optimal healing period for mice with minimal collagen production in the late fetal stage, and this lasted 2 days after birth.     

The fetal cleft palate: II. Scarless healing after in utero repair of a congenital model.

The role of fetal surgery in the treatment of non-life-threatening congenital anomalies remains a source of much debate. Before such undertakings can be justified, models must be established that closely resemble the respective human anomalies, and the feasibility and safety of these in utero procedures must be demonstrated. The authors recently described and characterized a congenital model of cleft palate in the goat. The present work demonstrates the methodology they developed to successfully repair these congenital cleft palates in utero, and it shows palatal healing and development after repair. A surgically created cleft model was developed for comparative purposes. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Six pregnant goats were gavaged twice daily during gestational days 32 to 41 (term, 145 days) with a plant slurry of Nicotiana glauca containing the piperidine alkaloid anabasine; the 12 fetuses had complete congenital clefts of the secondary palate. Repair of the congenital clefts was performed at 85 days of gestation using a modified von Langenbeck technique employing lateral relaxing incisions with elevation and midline approximation of full-thickness, bilateral, mucoperiosteal palatal flaps followed by single-layer closure. Six congenitally clefted fetuses underwent in utero repair, six remained as unrepaired controls. Twelve normal fetuses underwent surgical cleft creation by excision of a 20 x 3 mm full-thickness midline section of the secondary palate extending from the alveolus to the uvula, at 85 days of gestation. Six surgically clefted fetuses underwent concurrent repair of the cleft at that time; six clefted fetuses remained as unrepaired controls. At 2 weeks of age, no congenitally or surgically created clefts repaired in utero demonstrated gross or histologic evidence of scar formation. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. Cross-section through the mid-portion of the repaired congenitally clefted palates demonstrated reconstitution of a bilaminar palate, with distinct oral and nasal mucosal layers, after single-layer repair. In utero cleft palate repair is technically feasible and results in scarless healing of the mucoperiosteum and velum. The present work represents the first in utero repair of a congenital cleft palate model in any species. The use of a congenital cleft palate model that can be consistently reproduced with high predictability and little variation represents the ideal experimental situation. It provides an opportunity to manipulate specific variables, assess the influence of each change on the outcome and, subsequently, extrapolate such findings to the clinical arena with a greater degree of relevance.     

Growth of the cleft lip following a triangular flap repair

This study involves 50 children who had a triangular flap repair for unilateral cleft lip. They have been followed for 5 to 14 years by serial measurements, photographs, and clinical evaluation. During the first 5 years, the lips were designed to allow for future growth. The expected growth did not occur. During the second 5 years, the lip length was designed equal to the normal side with the belief that unequal growth does not occur. In this group, the results supported the premise that deviation from the correct lip length would now be equally divided between too long and too short. None of the entire group has a lip which started too short becoming equal or starting equal to become too long. It is the conclusion of the authors that a repaired unilateral cleft lip retains the configuration and length determined at the time of the initial repair.     

Upper lip measurements at the time of surgery and follow-up after modified rotation-advancement flap repair in unilateral cleft lip patients

The purpose of this prospective study was to determine whether unilateral cleft lip repaired by the rotation-advancement flap will grow short on the repaired side. This study involved 56 patients with nonsyndromic unilateral cleft lip (31 with complete and 25 with incomplete cleft lip) who underwent a rotation-advancement flap repair by a single surgeon between 1989 and 1997. Eleven patients were lost to follow-up. Forty-five patients have been followed for a varying period of between 8 and 84 months (mean = 37 months). The upper lip was measured immediately after the lip repair and follow-up using calipers. The growth ratios of vertical, horizontal, and nostril sill dimensions were compared between the cleft side and the noncleft side of the same face. Statistical analysis was performed to compare the growths between the cleft and noncleft sides. There was not a significant difference in the growth ratios of vertical (Wilcoxon signed rank test, p = 0.85) and horizontal dimensions (Student's t test, p = 0.18) between the cleft and noncleft sides. There was, however, a statistically significant difference in the growth ratios of nostril sill width between the cleft and noncleft sides (Student's t test, p = 0.02). Our findings indicated that a repaired unilateral cleft retained the vertical and horizontal dimensions determined at the time of the initial repair.     

The fetal cleft palate: III. Ultrastructural and functional analysis of palatal development following in utero repair of the congenital model

The role of fetal surgery in the management of congenital anomalies and intrauterine abnormalities is appropriately restricted on the basis of feasibility and risk-to-benefit analyses of intrauterine intervention. Recently, the authors demonstrated that in utero cleft palate repair of the congenital caprine model is technically feasible and results in scarless healing of the mucoperiosteum and velum, with subsequent development of a potentially functional bilaminar palate with distinct oral and nasal mucosal layers, following single-layer repair of the fetal mucoperiosteal flaps. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. The present work investigated the ultrastructural and functional aspects of the palate following in utero cleft repair to determine what benefits might be derived from fetal intervention. Six goats pregnant with twins were gavaged twice daily for 10 days (gestational days 32 to 41; term, 145 days) with dry, ground Nicotiana glauca plant delivering between 2.4 and 14 mg/kg per day of anabasine, doses that were adjusted in response to mater-nal toxicity. At 85 days' gestation, six fetuses underwent in utero palatoplasty using a modified von Langenbeck technique with elevation of bilateral mucoperiosteal flaps and lateral relaxing incisions. A single-layer repair of the mucoperiosteal flaps was performed using interrupted 6-0 Vicryl sutures. Six fetuses remained as unrepaired clefted controls. Six months after in utero palatoplasty, each group of goats underwent nasoendoscopy to evaluate palatal function; two unclefted 6-month-old goats served as controls. Subsequently, soft palate muscle was harvested from each of the goats and was evaluated by light and electron microscopy. Velar muscle was also harvested from the unclefted control goats and was similarly studied. Nasoendoscopy demonstrated functional palates capable of dynamic velopharyngeal closure following in utero cleft repair; this motion was similar to that observed in unclefted animals. Unrepaired clefted goats did not demonstrate any evidence of velar motion or velopharyngeal closure. Soft palate muscle from this group demonstrated evidence of myofibril degeneration, atrophy, and loss compared with unclefted control velar muscle. Ultrastructural changes included sarcomere "scalloping, " partial Z-line degeneration and loss, and progressive I-band degeneration and loss. Repaired clefted soft palate muscle was remarkably similar to unclefted control muscle. Significantly less myofibril, Z-line, and I-band degeneration and loss were observed with minimal evidence of sarcomere scalloping. In utero cleft palate repair results in a functional soft palate with restoration of ultrastructural architecture of the velum. These findings were attributed to reconstitution of the velar muscular sling, which is disrupted during the clefting process and remains abnormally inserted into the posterior edge of the palatal bone and along the bony cleft. Although repaired velar muscle does demonstrate some evidence of ultrastructural change compared with control muscle, these findings are significantly less pronounced than those observed in the unrepaired clefted muscle.     

In utero cleft lip repair in A/J mice

Reconstructive in utero microsurgery for repair of unilateral cleft lips has been technically achieved in the A/J mouse fetus. The period of gestation was undisturbed, and following birth, the gross and histologic appearance of the lips was nearly normal with no evidence of scar formation. The absence of a lip scar after human cheiloplasty may require the as yet undefined advantages of fetal wound healing.     

Nasal expansion in the fetal lamb: a first step toward management of cleft nasal deformity in utero

The cleft nasal deformity, a combination of malpositioned cartilage and tissue and postrepair scarring, is a difficult problem to correct. To harness the potential of scarless fetal wound healing, in utero repair of cleft lip and palate deformities has been studied but the fetal cleft nose deformity has not been addressed. The purpose of this study was to manipulate the fetal nasal shape in utero as a first step toward restoration of normal nasal form in cleft nasal deformities. To do this, preformed hypertonic sponges were placed into the right nostril of eight fetal lambs during the second trimester (when scarless cutaneous wound repair is known to occur). Then, the size and shape of fetal nasal structures were analyzed after selected time periods (1, 2, and 6 weeks) with measurements, routine histologic examination, and three-dimensional computed tomographic scans of the experimentally expanded noses compared with the control nonexpanded noses of the birth twins or age-matched specimens. Results showed that experimentally expanded nasal structures had markedly increased in septal length measurement, in nostril area (doubled), and in intranasal volume (more than doubled). Histology showed normal cellular elements without scarring in the tissue sections from the expanded nasal areas. In conclusion, the shape of nasal tissue can be manipulated without scarring in second-trimester fetal lambs after placement of a nasal expansion device. This study is an experimental first step toward restoring normal nasal form by repositioning alar cartilages and soft tissue during fetal cleft repair.     

Simultaneous cleft lip and palate repair: an experimental study in beagles

This study was designed to test the hypothesis that simultaneous lip and palate repair results in more severe craniofacial growth aberrations than lip repair or palate repair performed separately. Seventy-six purebred beagles were divided into five groups. Two of these groups were controls (unoperated and unrepaired animals); the three remaining groups were experimental (in one group only the lip was repaired, in another only the palate was repaired, and in the last the lip and palate were repaired simultaneously). Cephalometric measurements were analyzed using univariate and multivariate statistical techniques. In multivariate analysis, stepwise multiple regression and discrimination were applied to precisely assess the effects of the various surgical procedures. The results of this study indicate that simultaneous lip and palate repair results in more severe craniofacial growth aberrations than lip repair or palate repair performed separately.     

Primary repair of bilateral cleft lip and nasal deformity.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. List five principles that guide synchronous repair of bilateral complete cleft lip and nasal deformity. 2. Explain how different growth rates for the principal nasolabial features are applied during primary repair. 3. Describe two approaches for positioning the alar cartilages to form the columella. 4. Discuss the influences on referral patterns for a newborn with bilateral cleft lip. --Traditional repair of bilateral cleft lip focused on labial closure but accentuated the nasal deformities, which were addressed later. By the end of the past century, single-staged labial closure had replaced the old multistaged procedures and the technical emphasis had begun to shift from secondary to primary nasal correction. Now, presurgical maxillary orthopedics sets the bony foundation for synchronous nasolabial repair and for closure of the alveolar clefts. The study of normal nasolabial growth and the typical stigmata of the conventional methods provides the necessary foreknowledge to guide surgical sculpture in three dimensions and to anticipate the fourth dimension. The convergence of several forces are changing referral lines for children born with bilateral cleft lip. These include affirmation of centers of excellence, surgeons' self-regulation, prenatal diagnosis, economics of health-care delivery, and increasing parental sophistication. These pressures are not necessarily in conflict. Care by a subspecialized plastic surgeon and experienced team is in the best interests of the child and the third-party payer.     

The Tennison Lip repair revisited

Tennison presented his method for the repair of the single cleft. He was the first to recognize and to preserve the cupid's bow by lowering the peak in the margin of the cleft. He incised the medial side of the cleft and filled the space with a triangular flap from the lateral side. We have modified the Tennison repair based on the vertical height of the normal side, as did Randall and Hagerty. We make the lip 1 mm shorter in the vertical height than the normal side because some of our repairs were too long. Other modifications include a 1-mm offset at the vermilion, and in certain lips that are too long in the newborn, a triangle is excised beneath the alar base to shorten the vertical height. The details for planning the incisions and accomplishing the surgery are given. Certain patients required a V-to-Y procedure to augment a vermilion deficiency, but none of these patients required a secondary procedure. This emphasizes the need for careful planning to get it right at the primary repair. The operation is indicated for the incomplete cleft to the very wide cleft, and in no patient was a lip adhesion required. We no longer operate on the nose at the primary repair.     

Bilateral cleft lip and nasal repair

SUMMARY: The bilateral cleft lip and nasal repair has remained a challenging endeavor. Techniques have evolved to address concerns over unsatisfactory features and stigmata of the surgery. The authors present an approach to this complex clinical problem that modifies traditional repairs described by Millard and Manchester. The senior author (H.S.B.) has developed this technique with over 25 years of surgical experience dealing with the bilateral cleft lip. This staged lip and nasal repair provides excellent nasal projection, lip function, and aesthetic outcomes. Lip repair is performed at 3 months of age. Columellar lengthening is performed at approximately 18 months of age. A key component of this repair focuses on reconstruction of the central tubercle. A triangular prolabial dry vermilion flap is augmented by lateral lip vermilion flaps that include the profundus muscle of the orbicularis oris. This minimizes lateral lip segment sacrifice and provides improved central vermilion fullness, which is often deficient in traditional repairs. The authors present the surgical technique and examples of their clinical results.     

Functional cleft lip repair: a sequential, layered closure with orbicularis muscle realignment

A lip repair based on anatomic and electric stimulation studies of the orbicularis muscle in unilateral cleft lip has previously been reported by one of the authors. Following some early modifications, this technique has been used on 125 primary lip repairs. The details of the present technique are described here. The advantages of the procedure, in addition to its functional reconstruction of the orbicularis muscle, are in its applicability to clefts of all widths and superior scar formation. The sequential nature of the procedure and freedom from commitment to a fixed, measured pattern at the outset makes the teaching of the method easier and the achievement of a pleasing result more predictable.     

The influence of lip repair with and without soft-tissue undermining on facial growth in beagles

The present study was designed to test the hypothesis that undermining of the soft tissues on the surface of the maxilla at the time of lip repair in unilateral cleft lip, alveolus, and palate results in more severe craniofacial growth aberrations than lip repair alone. Sixty-seven purebred beagles were used in this experiment. The animals were divided into four groups: two control groups (unoperated and unrepaired) and two experimental groups (lip repair without undermining and lip repair with undermining). Lip pressures were monitored in all groups. Significantly higher lip pressures were observed in animals with soft-tissue undermining. Cephalometric measurements were analyzed using univariate and multivariate techniques. The results of this study indicate that lip repair performed with soft-tissue undermining results in more severe craniofacial growth aberrations than lip repair performed alone.     

Repair of cleft lip with nonsurgical correction of nasal deformity in the early neonatal period

Auricular cartilage is soft and plastic at birth, so that congenital auricular deformities can easily be corrected nonsurgically in the early neonatal period. However, as the infant grows older, the flexibility of the auricle decreases. Alar cartilage exhibits the same elasticity as auricular cartilage in the early neonate. When a cleft lip is repaired, typically when the infant is about 3 months of age, it becomes difficult to correct the nasal deformity without surgical intervention. However, based on our experience, there is a fair possibility of correcting the cleft lip nasal deformity with a nonsurgical procedure in the early neonatal period. We performed cleft lip repair accompanied by nonsurgical correction of the nasal deformity in 44 neonates aged 2 to 7 days. A special retainer was placed in the affected nostril for 3 months. Following observation of 31 infants for 12 months or longer, their nasal shapes and symmetry were considered superior to those conventionally operated on at about 3 months of age. Except for one nasal infection, there were no complications.     

Analysis of the lengthening effect of the muscle repair in functional cleft lip repair

In 14 patients undergoing functional cleft lip repair, changes in the lengths of the key lip segments were measured preoperatively, after the muscle layer was repaired, and after the skin was repaired using pieces of wire bent to follow the curves of the lip in three dimensions. The cleft side of the lip was shorter than the normal side in the vertical and horizontal dimensions. Freeing the muscle from its dermal insertions, splitting it, and advancing it into the medial side of the cleft lengthened the cleft side of the lip vertically and horizontally. The Z-plasty skin repair further lengthened the cleft side of the lip in the vertical dimension. The lengthening effect of the muscle repair appears to be the result of the loose skin redraping over the dissected muscle and further explains elimination of the orbicularis bulge and superior scar formation in the functional cleft lip repair.     

Improved primary surgical and dental treatment of clefts

The improved combination of surgical and dental teamwork in the primary treatment of clefts presented here is consistent with principles. In fact, this is a staged design for correction of classic clefts of the lip and palate that, based on biological principles, facilitates the continuance of the failed embryonic "migrations" toward a normal end point. Positioning of the alveolar segments, dissection of mucoperiosteum out of the cleft, and union of mucoperiosteum across the alveolar and anterior hard palate cleft make it possible to create a periosteal tunnel across the bony gap and set up a condition conducive to bone formation and eventual tooth eruption in the cleft area. Lip closure by adhesion reduces the tension of the primary lip closure and allows gentle molding until solidification of the arch occurs. Thus a complete cleft has been rendered an incomplete cleft. With a balanced, stabilized maxillary platform, the definitive lip and nose corrections can be carried to completion early (by 2 to 4 years of age). These planned actions bypass a persistent cleft, fistulas, raw areas, malposition of alveolar segments, and probably the necessity for later bone grafting. The only question not totally answered is the effect of this approach on final growth. Although most reports seem to indicate that growth has and will proceed within normal limits, another 10 years of careful follow-up is indicated and, in fact, is in progress.     

Modified technique of presurgical infant maxillary orthopedics for complete bilateral cleft lip and palate

This article introduces technical modifications to the conventional presurgical infant maxillary orthopedics device for newborns with complete bilateral cleft lip and palate, providing procedural simplicity and efficiency as well as therapeutic efficacy. The modifications incorporate a wax block-out on the stone model prior to device fabrication in a manner that the need for periodic acrylic addition and removal is not required, and thus eliminates the risk of natural maxillary growth restriction during infant maxillary orthopedics treatment. The premaxilla is completely excluded from the acrylic palatal plate and is repositioned primarily by the bilateral labial tape alone. In addition, nasal stent wires are installed on the same day of the palatal plate delivery to establish a tripod-like retention mechanism for the intraoral device to be able to replace the conventional mechanical lock-type retention methods. Applying these modifications, infant maxillary orthopedics treatment objectives for bilateral cleft lip and palate can be successfully achieved within 8 weeks of treatment, and the definitive primary cleft lip repair can be performed within 3-4 months of infant maxillary orthopedics treatment at our Center.     

Orthognathic surgery in cleft patients treated by early bone grafting

For the past 25 years at Children's Memorial Hospital in Chicago a protocol has been followed for complete clefts that involves placement of an infant maxillary orthopedic appliance prior to lip closure, surgical closure of the lip, autogenous split-rib grafts to the alveolus to stabilize maxillary segments, and palatal closure, generally within the first year of life. The oldest 36 patients whose skeletal growth was for all practical purposes finished have been followed to determine the need for and type of orthognathic surgery. Of the total sample, 8 patients (22.2 percent) required some type of sagittal orthognathic surgery (1 patient in this group also required vertical maxillary alignment) and 2 patients required maxillary augmentation only in the form of an onlay graft. This report may serve as a baseline for others who wish to report on the incidence and type of orthognathic surgery in their cleft palate centers.