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.     

Pharmacologic manipulation of postoperative labial wound contraction and midfacial growth in rabbits

Recent experimental work has suggested that increased lip pressure and scar contraction following lip repair with wide soft-tissue undermining may, in part, contribute to midfacial growth inhibition. The present study was designed to test this hypothesis through the application of pharmacologic agents reported to minimize scar contraction. Thirty-six 6-week-old rabbits were divided into six groups: unoperated controls, rabbits with surgically created defects left unrepaired (surgical controls), and four groups of rabbits with surgically created defects with lip repair and wide undermining on the maxillary surface. Animals with lip repair received either no injections or labial subcutaneous injections of distilled water (route-of-injection controls), normal saline, or papaverine hydrochloride for 2 weeks postoperatively. Rabbits with lip repair and saline or papaverine injections showed significantly (p less than 0.05) decreased lip pressure, relatively hypotonic orbicularis oris muscle EMG activity on the cleft lip side, and greater anteroposterior facial growth (assessed radiologically) from 2 to 24 weeks postoperatively compared with rabbits with lip repair and postoperatively compared with rabbits with lip repair and no injections or distilled water injections. Preliminary results suggest that wound contraction following lip repair and soft-tissue undermining may contribute to mid-facial growth inhibition, which may be reduced by pharmacologic manipulations in the rabbit model.     

Facial skeletal growth after timed soft-tissue undermining.

This study was designed to answer the following questions: (1) Does aggressive bilateral soft-tissue undermining of the nasomaxillary complex in an immature animal without an iatrogenically produced cleft lip significantly inhibit growth? (2) If so, is the early timing of this undermining crucial? Fifty New Zealand White rabbits were used in this study, and bilateral buccal sulcus incisions with extensive nasomaxillary supraperiosteal undermining were performed in the experimental groups. There were five groups: (1) control, (2) undermining at 3 to 4 days, (3) undermining at 7 to 10 days, (4) undermining at 18 to 21 days, and (5) undermining at 50 to 56 days. The animals were sacrificed at 6 months of age, and direct osteometric measurements were made. Results demonstrated that a significantly retruded, constricted, and vertically shortened maxilla was produced as a direct result of bilateral nasomaxillary soft-tissue undermining alone regardless of the timing.     

A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model.

Successful open repair of a cleft lip in utero has the advantage of scarless wound healing in the fetus. Unfortunately, no long-term outcome studies have been performed to evaluate the efficacy of these repairs. Moreover, no study to date has compared the long-term results of an in utero cleft lip repair to a similar, control-matched, newborn cleft repair. This study was performed to evaluate the 9-month outcome of in utero cleft lip surgery compared with an identical cleft lip repair performed on infant lambs. In utero epithelialized cleft lips were created through an open hysterotomy in sixteen 65-day-old fetal lambs (term = 140 days) using methods described by Longaker et al. Eight of 16 animals underwent subsequent in utero repair of these clefts at 90 days gestational age. The repair of the remaining eight animals was delayed until 1 week postpartum. At 9 months, the animals were analyzed for changes in lip contour and for the degree of scarring by hematoxylin and eosin and Masson's trichrome collagen staining. Two animals in each group died from preterm labor. Of the animals that survived to term, all repaired lips had some degree of abnormality postoperatively. One of six lips repaired in utero dehisced before delivery. Three of six neonatal repairs dehisced in the first postoperative month. In the remaining animals with intact lip repairs, the vertical lip height on the repaired side was an average of 9 to 12 mm shorter than the normal lip in both the in utero and neonatally repaired animals. Phenotypically, the postnatally repaired animals had more lip distortion and visible notching. Histologically, the in utero repair was scarless and the neonatal repairs had scar throughout the entire vertical height of the lip with an associated loss of hair in this region. Maxillary growth was also evaluated. There was no inhibition of maxillary growth in the animals that underwent in utero cleft lip repair. However, in the neonatal repair group, significant maxillary retrusion was evident. Compared with the cleft side of the maxilla, horizontal growth was decreased by 11 percent (p = 0.01). Compared with the intrauterine repair group, there was a 17-percent decrease in horizontal maxillary width (p = 0.01). Straight-line in utero repair of a cleft lip produces a better long-term result in terms of maxillary growth than a similar repair performed postnatally in the ovine model. There was no diminution in maxillary growth in the animals treated in utero. Histologically, in utero repair of clefts was indeed scarless. However, both lip repairs produced lips that were significantly shorter than their contralateral noncleft sides. This degree of lip shortening would require a secondary lip revision, thereby defeating the purpose of performing an intrauterine repair. Comparisons now need to be made between in utero and neonatal repairs using a Millard-type rotation advancement technique before intrauterine treatment can be considered to be more beneficial than our current treatment modalities.     

Craniofacial growth in subjects with unilateral complete cleft lip and palate, and unilateral incomplete cleft lip, from 2 to 22 months of age

This paper reports a longitudinal quantitative cephalometric analysis of the craniofacial growth in subjects with unilateral complete cleft lip and palate (UCCLP), and unilateral incomplete cleft lip (UICL), from 2 to 22 months of age. The purpose of the study was to determine the amount and direction of growth in UCCLP compared to UICL (control group) from 2 months of age (just prior to lip repair) to 22 months of age, 20 months later. The sample comprised of 49 subjects with UCCLP (37 males and 11 females) and 45 with UICL (29 males and 16 females). The cephalometric analysis of the craniofacial morphology included lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. A valid common coordinate system (registration according to the n-s line in the lateral projection, latero-orbitale line in the frontal projection, and meatus acusticus externus line in the axial projection for the landmark positions at examination 1 and 2) was ascertained. The growth at a specific anatomical location in a patient was defined as the displacement vector from the coordinate of the corresponding landmark in the X-ray at examination 1 to its coordinate at examination 2, corrected for X-ray magnification. The growth of an anatomical region in a patient was assessed by investigating the growth pattern formed by a collection of individual growth vectors in that region. The amount of growth in the UCCLP and UICL group was very similar. The general craniofacial growth pattern, in terms of the direction of growth, was also fairly similar in the UCCLP group and the control group. However, the maxilla and mandible showed a more vertical growth pattern than that observed in the control group. This study confirms that UCCLP is a localized deviation, and not a craniofacial anomaly, due to the fact that a normal growth potential has been observed in all craniofacial regions, except where the growth had been directly influenced by surgical intervention. Furthermore, the vertical growth pattern of the maxilla and mandible supports the hypothesis of a special facial type in cleft lip and palate individuals, and the facial type as a liability factor increasing the probability of cleft lip and palate.     

Does interference with mucoperiosteum and palatal bone affect craniofacial growth? An experimental study in beagles

This study was designed to assess the effects of raising mucoperiosteal flaps and exposing palatal bone at the time of palatoplasty. Using 62 beagle puppies as subjects, we tested the hypothesis that raising mucoperiosteal flaps does not interfere with craniofacial growth. We further hypothesized that the size of the area of bone exposed following palatoplasty does affect subsequent craniofacial growth. The animals were divided into four groups: two control groups (unoperated and unrepaired) and two experimental groups. In the first experimental group, two-flap palatoplasty was used to close the surgically induced palatal defect, leaving narrow strips (0 to 2.5 mm) of bone exposed lateral to the flaps. In the second group, one flap was raised to close the defect, leaving a wide area (5 to 6 mm) of palatal bone exposed on one side. Thirty-four direct craniometric measurements were analyzed. Animals that had elevation of both mucoperiosteal flaps with narrow strips of denuded bone on both sides had less severe craniofacial growth aberrations than those in which the defect was left unrepaired or was repaired with one mucoperiosteal flap leaving a wider area of bare bone exposed. These findings suggest that raising mucoperiosteal flaps is less detrimental to craniofacial growth than leaving large areas of exposed palatal bone.     

Lip pressure changes following lip repair in infants with unilateral clefts of the lip and palate

The present study was designed to quantitatively assess lip pressure changes following cleft lip repair in infants with unilateral cleft lip, alveolus, and palate. Lip pressure measurements were taken using an electronic transducer system developed especially for this study. Lip pressure was monitored from 3 months (preoperatively) through 2 years of age in cleft and normal control children. Findings from the present study confirm the hypothesis that lip repair in infants with unilateral cleft lip and palate significantly increases lip pressure and that increased lip pressure remains significantly higher than in normal control children for the 2-year duration of the study. Thus increased lip pressure when the palate is unrepaired has to be considered as a factor modulating subsequent craniofacial growth.     

The influence of incompetent lip seal on the growth and development of craniofacial complex

Abnormal orofacial functions in the period of growth and development can cause morphological anomalies of the craniofacial complex. The aim of this study was to determine the correlation between open mouth posture and morphology of craniofacial complex. The shape, size and relationships of skeletal parts of craniofacial complex were determined by analysis of lateral cephalograms in the sample of 84 children--45 girls and 39 boys (aged 8.96 +/- 0.66 years). The sample was divided into two groups--lip competence and lip incompetence group. Differences in cephalometric values between observed groups were found. The values of inclination of lower central incisors (angle ILi/NB), interbasal angle (NL/NSL), angle between occlusal and mandibular plane and anterior lower facial height were significantly higher in the group with open mouth posture. It can be concluded that lip incompetence plays an important role in growth and development of craniofacial complex.     

A comparison of the craniofacial morphology in 2-month-old unoperated infants with unilateral complete cleft lip and palate, and unilateral incomplete cleft lip.

This paper reports a cephalometric analysis of the craniofacial morphology in infants with unoperated unilateral complete cleft lip and palate (UCCLP) and unoperated unilateral incomplete cleft lip (UICL). The purpose of the study was to determine the nature and extent of the craniofacial deviations in UCCLP as compared to the morphology in UICL, which has previously been shown to be close to normal. The samples comprised 82 infants with UCCLP (58 males and 24 females) and 75 with UICL (48 males and 27 females). The mean age was about 2 months in both groups. The cephalometric analysis of craniofacial morphology included the lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. The most pronounced deviations in the UCCLP group were observed in the maxillary complex and the mandible. The most striking findings were: markedly increased width of the maxilla, a short mandible, and bimaxillary retrognathia except for the premaxillary area, which was relatively protruding and asymmetric. The study did not support the hypothesis previously suggested in the literature that cleft lip and palate is a craniofacial anomaly as size and shape of the calvaria and cranial base were found to be normal. The etiology of cleft lip and palate is still incompletely understood. Based on the present study, we suggest that facial type may be a liability factor that could represent a developmental threshold increasing the probability of cleft lip and palate.     

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.     

Early definitive bone and soft-tissue reconstruction of major gunshot wounds of the face

The use of craniofacial surgical techniques, extended open reduction, rigid fixation with plates and screws, and the replacement of severely damaged or missing bone with immediate bone grafting in the treatment of complex facial fractures has been applied to the management of severe gunshot wounds of the face. Early definitive bone and soft-tissue reconstruction has been performed in 37 patients. One-hundred and seventy-seven primary bone grafts were utilized in 33 patients for orbital, nasal, zygomatic, and maxillary reconstruction. Twenty-six patients required mandibular repair with compression or reconstruction plates. Soft-tissue reconstruction was provided by a combination of flaps. Four patients had extensive soft-tissue loss replaced by free vascularized omental flaps. The omentum provided circumferential coverage of the mandibular reconstruction and reconstruction of the floor of the mouth and was then tunneled in a circle through both cheeks into the middle and upper face. The omentum reconstructed deficits in the hard palate and upper buccal sulcus and was then wrapped around all zygomatic, orbital, and midfacial bone grafts and used to fill in dead space in the maxillary, ethmoid, and frontal sinuses. The omentum is not used to provide contour and bulk, but to cover bone grafts and plates and fill in dead space. Carefully shaped bone grafts provide the correct craniofacial scaffold. Early restoration of a midfacial bony scaffold and the prevention of soft-tissue contraction facilitate secondary reconstruction. Four late total nasal reconstructions with tissue-expanded forehead skin wrapped around bone grafts were performed.     

Experience with the functional cleft lip repair

The first 12 functional cleft lip repairs performed on unselected consecutive patients immediately following the completion of training by the author are presented. Previous reports on this cleft lip repair have shown excellent results but have always been based on patients operated on by the originator of the procedure. This report gives credence to the ease with which a cleft lip repair that gives reproducible good results can be taught and learned even by plastic surgeons with limited experience. It reviews the technical steps of the procedure, which emphasizes wide undermining and release of the orbicularis oris muscle on the lateral side of the cleft to allow redraping and lengthening of the lip skin, step-by-step layered closure of the mucosa, muscle, and skin, and further vertical lengthening of the lip with a Z-plasty skin closure. Three elements that are difficult to achieve or restore with cleft lip revision are evaluated: (1) achievement of a good skin scar, (2) maintenance of the alar-facial groove, and (3) achievement of adequate lip height without sacrificing horizontal lip length. Ten of the 12 patients had a satisfactory scar, 9 patients had a good alar-facial groove, and all patients had a normal-appearing horizontal lip length. Nine patients required secondary surgery; however, in six patients, this included correction of the nasal deformity that was not corrected at the time of cleft lip repair.     

Clastogenic effect of copper deficiency in cattle

Copper plays an essential role as a micronutrient. Deficiency of this element (hypocuprosis) in experimental and domestic animals has a severe impact on growth as well as on reproduction. The occurrence of lesions during hypocuprosis is correlated with the depletion of an enzymatic group in which copper takes part. The aim of this work was to analyse chromosomal aberrations in Aberdeen Angus cows of the province of Buenos Aires in relation with the Cu plasma levels. Short term lymphocyte cultures were made from samples obtained from four groups of animals: two groups with normal levels of copper in plasma and two groups with severe hypocupremia. This analysis showed a significant increase of the frequency of chromosomal aberrations (p<0.001) in the hypocupremic groups in relation with control groups. Finally, the Spearman correlation analysis showed a significant negative association (p<0.05) between copper levels and the yield of chromosomal aberrations. The increase of the frequencies of chromosomal aberrations found in the hypocupremic groups could be explained by the higher oxidative stress suffered by these animals. A lower catalytic activity of enzymes such as Cu/Zn superoxide dismutase (Cu/Zn-SOD) and cytochrome-c oxidase could increase the intracellular production of active oxygen species (O(2)(-), H(2)O(2) and OH(o)) with the consequent clastogenic effects.     

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.     

Health-related quality of life in children with craniofacial anomalies

The purpose of this study was to examine parents' perceptions of the health and health-related quality of life in a series of children and adolescents with cleft and other craniofacial anomalies. The subjects for this prospective study were a consecutive series of 54 children and adolescents presenting to an outpatient craniofacial anomalies surgery clinic, ages 5 to 18 years (mean, 8.9 +/- 4.2 years), 50 percent with cleft lip and/or palate, 9 percent synostotic (two coronal, two bicoronal, and one sagittal), 17 percent syndromic (two Apert, one Crouzon, one Noonan, two Goldenhar, two Smith-Lemli-Opitz, and one brachio-oto-renal), and 24 percent with other diagnoses. Subjects were divided into two groups, those with primary cleft lip and/or palate and those with other craniofacial anomalies. Health and health-related quality of life were assessed with the Child Health Questionnaire version PF28, a reliable and valid 28-Likert-item questionnaire completed by parents and yielding physical and psychosocial status scale scores. Physical and psychosocial scale scores largely fell within normal limits for the subset of children with cleft lip and/or palate. There were significant group differences in parents' ratings of global health status, with greater health concerns noted in the non-cleft lip and/or palate group. There were no significant associations between either age or sex and physical or psychosocial health. Physical health, behavior, and psychological status were highly correlated. Using a health status and quality-of-life assessment instrument, findings indicate perceived health differences between groups with and without primary cleft lip and/or palate. In contrast to normative data with the Child Health Questionnaire, findings suggest that there is a significant association between perceived physical health and psychosocial adjustment in the population of children with craniofacial anomalies. The significant perceived health needs of the non-cleft lip and/or palate group and the association between physical health and psychological adjustment highlight the importance of the interdisciplinary nature of craniofacial teams.     

Three-dimensional rejuvenation of the midface: volumetric resculpture by malar imbrication

The rejuvenation technique of malar imbrication, which avoids dissection in the plane of the seventh cranial nerve, is presented to address the author's altered priorities in midfacial rejuvenation. These priorities target volumetric over tension-based goals in a manner that is simpler, safer, and more sculpturally effective than existing techniques. Volumetric manipulations in the subperiosteal and subcutaneous planes also bring substantial rejuvenation to the periorbital and perioral regions, without lip or lower lid incisions. Fourteen of the 172 patients (8 percent) who underwent consecutive procedures for primary facial rejuvenation suffered temporary upper lip paresis. Other complications were infrequent and limited. One patient underwent reoperation for asymmetry. Increased postoperative swelling and recovery are a necessary consequence of the subperiosteal component, just as increased operative time attends the wide undermining of the subcutaneous component. Despite these liabilities, the author recommends adding volumetric resculpture to the existing conventional tools of soft-tissue displacement under tension and topical resurfacing in pursuit of safer, more effective, and more natural rejuvenation of the aging face.     

The role of tissue expansion in the treatment of atypical facial clefting

Tissue expansion can be a valuable tool in the reconstruction of soft-tissue defects in craniofacial clefts. To our knowledge, there have been no reports in the literature of the use of tissue expanders to help solve this problem. We report the case of a child with an atypical Tessier no. 3 craniofacial cleft who had a forehead tissue expander placed, inflated, and thus used to provide sufficient local facial skin for repair of the soft-tissue defect.     

The cleft lip lower-lip deformity

A patient with a repaired upper lip cleft may acquire a deformity in the lower lip. Records of 63 cleft lip patients who exhibited lower-lip abnormalities were analyzed in order to characterize the soft-tissue and skeletal configuration. The typical deformity was a hypertrophied, superiorly displaced, and anteriorly rotated lower lip. Skeletal analysis of the mandible revealed a variable and inconsistent degree of vertical elongation with posterior displacement of the chin. Operative correction of the cleft lip lower-lip deformity required evaluation of both the soft-tissue and skeletal abnormalities. Soft-tissue procedures gave permanent correction, provided there was a normal maxillary-mandibular relationship. Skeletal correction alone did not completely rectify the abnormal lower-lip posture.     

Accelerated Wound Closure In Vitro by Fibroblasts from a Subgroup of Cleft Lip/Palate Patients: Role of Transforming Growth Factor-α

In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely “fast”, “intermediate”, and “slow”. Most cleft lip/palate fibroblasts were distributed between the “fast” (5 strains) and the “intermediate” group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the “fast” group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the “intermediate” migratory group to the level of the “fast”, but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of “fast” cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling.     

Common genetic and environmental factors among craniofacial traits in Belgian nuclear families: Comparing skeletal and soft-tissue related phenotypes

The major objective of this study was to determine the possible effects of common genetic and environmental factors among 18 craniofacial anthropometric traits, with special attention to the differences between skeletal and soft-tissue related phenotypes. The studied sample consisted of 122 nuclear families living in Brussels and included 251 males and 258 females aged from 13 to 72 years. Univariate and bivariate quantitative genetic analyses were performed using a variance components procedure implemented in SOLAR software.All phenotypes were significantly influenced by additive genetic factors with heritability estimates ranging from 0.46 (nose height) to 0.72 (external biocular breadth). Sex, age and their interactions explained 7-46% of the total phenotypic variance of the traits. Bivariate analysis revealed that several traits share a common genetic and/or environmental basis while other traits show genetic and environmental independence from one another. More and greater genetic and environmental correlations were observed among skeletal phenotypes, than among soft-tissue traits and between both categories. Apart from the tissue composition, other characteristics of the craniofacial morphology such as the orientation (e.g. heights, breadths) have shown to be important factors in determining pleiotropy and common environmental effects between some pairs of traits. In conclusion, the results confirm that overall head configuration is largely determined by additive genetic effects, and that common genetic and environmental factors affecting craniofacial size and shape are stronger for the skeletal traits than for the soft-tissue traits.