Cleft-related nose deformation evaluation and measurement methods. Literature review

INTRODUCTION: Rhinoplasty for the cleft lip and palate patient is very challenging and surgical outcome of the nose is difficult to evaluate. Discussions of aesthetic evaluation of the nose in cleft lip and palate patients remain problematical. Many different nose aesthetic evaluation methods have been described in the literature; they differ even among articles published in a single year. AIM: To analyse the literature concerning aesthetic evaluation of the nose in cleft lip and palate patients and to identify the most objective method for such evaluation postoperatively. MATERIAL AND METHODS: The literature was reviewed using MedLine and PubMed sources dated between January 1996 and December 2014. In total, 118 full text articles in English language were selected. Exclusion criteria were: case reports, surgical reviews, literature review, and single evaluations of nasal function. RESULTS: Measurements were obtained from two-dimensional images in 73 articles. Noses were evaluated from 3D images in 22 and by clinical examination in 15. Other methods were evaluation from dental/facial casts, cephalometric evaluation, computer tomography and video recording. In 26 articles some combination of methods was used. CONCLUSIONS: The most popular evaluation method is still two-dimensional photography and measurements using anthropometric facial landmarks. Measurements from three-dimensional images seem to be the most objective method and automated facial anthropometric landmark protraction seems to hold promise for the future.publishersversionPeer reviewe

Evaluation of the Multiple Tissue Factors in the Cartilage of Primary and Secondary Rhinoplasty in Cleft Lip and Palate Patients

Cleft lip and palate (CLP) is one of the craniofacial defects. The objective of this study was to identify the differences in appearance between the tissue factors in cartilage of CLP patients after primary and secondary rhinoplasty. Immunohistochemistry was performed with MMP-2, MMP-8, MMP-9, TIMP-2, IL-1α, IL-10, bFGF, and TGFβ1. The quantification of the structures was performed using a semi-quantitative census method. MMP-2, -9, IL-1a, and bFGF demonstrated higher number of positive cells in patients, while the number of MMP-8, IL-1a, -10 and TGFβ1 cells was higher or equal in the control subjects. The only statistically significant difference between CLP-operated patients was found in the TIMP-2 group, where the primary CLP patient group had a higher number of TIMP-2 positive chondrocytes than the secondary CLP patient group (U = 53.5; p = 0.021). The median value of the primary CLP group was ++ number of TIMP-2 positive chondrocytes compared to +++ in the secondary CLP group. No statistically significant difference was found between primary and secondary rhinoplasty patients for other tissue factors. Commonly, the rich expression of different tissue factors suggests a stimulation of higher elasticity in cleft affected cartilage. The statistically significant TIMP-2 elevation in primary operated cartilage indicates an impact of the selective tissue remodeling for hard tissue.publishersversionPeer reviewe

Expression of gene proteins, interleukins and β-defensin in cleft-affected tissue

OBJECTIVES: The aim of the study was to investigate cleft - affected tissues in children with cleft lip and palate in order to detect appearance of β-defensin, interleukins (IL) and gene proteins. MATERIAL AND METHODS: The study group included 10 patients with cleft lip and palate. During nose surgery tissue samples from bone and cartilage have been taken, and stained with immunohistochemistry for β-defensin 2, IL4, IL6, IL7, IL8, IL10 and MSX1, RYK, PAX9, IRF6 gene proteins. RESULTS: Results showed prominent expression of IL10 (mean value 47.28±4.26 in visual field) followed by IL7 (35.62±11.18) in cartilage of patients, but slightly less pronounced expression of IL8 (30.14±8.74), IL6 (22.52±10.88) and IL4 (14.81±6.94). The expression of β-defensin 2 was prominent (34.52±11.79) and similar to expression of IL7 in tissue samples of cartilage. MSX1, PAX9, RYK and IRF6 (17.67±5.94; 16.14±5.52; 16.57±5.22 and 11.86±4.21) in cartilage was less pronounced than interleukins and β-defensin 2. MSX1 (12.44±3.34), PAX9 (6.89±2.14), RYK (11.0±5.92) and IRF6 (9.1±4.76) gene proteins expression in bone showed mostly rare occurrence of positive structures. CONCLUSIONS: Significant expression of IL7 and β-defensin 2 and IL10 in cartilage proves the prominent immune response in cleft affected hard tissue. Mostly indistinct MSX1, PAX9, RYK and IRF6 gene proteins expression in bone might be an indicator of not complete cellular differentiation, proliferation and migration events in cleft disordered hard tissue.publishersversionPeer reviewe

Cleft Candidate Genes and Their Products in Human Unilateral Cleft Lip Tissue

Cleft lip and palate are common congenital pathologies that affect the human population worldwide. The formation of cleft lip is associated with multiple genes and their coded proteins, which regulate the development of craniofacial region, but the exact role of these factors is not always clear. The use of morphological studies for evaluation of human cleft-affected tissue has been limited because of insufficiency of available pathological material. The aim of this study was to detect and compare the immunohistochemical expression of cleft candidate gene coded proteins (DLX4, MSX2, HOXB3, SHH, PAX7, SOX3, WNT3A, and FOXE1) in the non-syndromic unilateral cleft lip patient tissue and control group tissue. A semiquantitative counting method was used to evaluate the tissue in biotin-streptavidin-stained slides. Statistically significant differences between the patient and control groups were found for the number of immunoreactive structures for SHH (p = 0.019) and FOXE1 (p = 0.011) in the connective tissue and SOX3 (p = 0.012) in the epithelium. Multiple statistically significant very strong and strong correlations were found between the immunoreactives in cleft-affected tissue. These significant differences and various correlations indicate that multiple morphopathogenetic pathways are possibly involved in unilateral cleft lip pathogenesis. Therefore, we further discuss these possible interactions.publishersversionPeer reviewe

Local expression of inflammatory cytokines in the facial tissue of children with a cleft lip and palate

The cleft lip and/or palate are among the most common congenital anomalies that occur in early development. Cytokines play an important role in the proliferation, growth, differentiation, survival and the functional activity of many cells and the upregulation of cytokines might be involved in the pathological processes of the maxillofacial region. The purpose of our study was to evaluate the expression of pro-inflammatory and anti-inflammatory cytokines in the facial tissue of children with the cleft lip and palate.The study involved 14 patients with the unilateral cleft lip and palate at the age of three months to 10 years and five months. Soft and hard palate tissue samples were collected during the primary cleft operation if the parents had given their informed written consent. All the tissue samples were stained with hematoxylin and eosin and by immunohistochemistry for IL-1α, IL-6, IL-8, IL-10 and TNF-α. The intensity of immunostaining was graded semiquantitatively.IL-1α containing structures were not detected in any of soft, cartilage and bone tissue samples, meanwhile IL-6, IL-8, IL-10 and TNF-α showed explicit expression. The expression of IL 6 was observed in the tissues of all the patients. IL-6 positive cells were found in the range from no positive to moderate of positive structures in the visual field. IL-8 positive osteocytes were found in the range from few positive to moderate, but IL-8 positive chondrocytes were found in abundance. IL-10 was richly secreted by osteocytes in bone and by chondrocytes in cartilage obtained from all the cases of plastic surgery. In all the cases we also observed numerous IL-10 positive gingival epithelial cells. Despite these data obtained, moderate to numerous macrophages and neutrophils expressed TNF-α.The sporadical and scarce expression of IL-6 indicates its insignificant role in the cleft lip and palate affected tissue. Rich cytokine IL-10 expression proves the compensated local anti-inflammatory effects of the cleft affected soft and hard tissue

Expression of growth factors and growth factor receptors in human cleft-affected tissue

OBJECTIVE. To investigate cleft disordered tissue in children with cleft palate and cleft lip with or without alveolar clefting for detection of local tissue growth factors and growth factor receptors and compare findings. Design. Morphological analysis of human tissue. Patients. Three groups were studied: 14 patients with cleft palate at the age from eight months to 18 years and two months, 12 patients with cleft lip with or without alveolar clefting in the age from four months to 15 years and four months and 11 control patients. RESULTS. In general, cleft palate disordered tissue showed more prominent expression of BMP2/4 (z=3.574; p=0.0004) and TGFβ (z=2.127; p=0.033), while expression of TGFBR3 significantly higher was only in connective tissue (z=3.822; p=0.0001). Cleft lip affected tissue showed significantly pronounced expression of FGFR1 in general as well as separately in epithelium. CONCLUSIONS. The marked and statistically significant expression of BMP 2/4 in cleft palate disordered soft tissue probably is delayed, but still proliferation and differentiation as well as tissue, especially, bone remodeling contributing signal. Cleft palate affected tissue show more prominent expression of TGFβ, still the weak regional expression of TGFβ type III receptors prove the disordered tissue growth and changed TGFβ signalling pathway in postnatal pathogenesis. In general, expression of TGFβ, BMP 2/4 and FGFR1 is significantly different, giving evidence to the involvement of these mentioned factors in the cleft severity morphopathogenesis.publishersversionPeer reviewe

Immunohistochemical analysis of nestin, CD34 and TGFβ3 in facial tissue of children with complete unilateral and bilateral cleft lip and palate

OBJECTIVE: This study aimed to evaluate levels of expression of nestin, CD34 and transforming growth factor β3 (TGFβ3) in facial tissue of children with complete unilateral (CU) and complete bilateral (CB) cleft lip and palate (CLP). MATERIALS AND METHODS: Twenty-nine CLP patients were enrolled in this study (18 boys and 11 girls). Tissue samples were collected during primary and repeated plastic surgery correction for CU (n=10) or CB (n=19) cleft palate (age range 3 months - 9 years, 6 months). Immunohistochemistry was used to assess levels of nestin, CD34 and TGFβ3. Positively stained cells were graded semi-quantitatively. Data were analyzed to compare cell counts between CUCLP and CBCLP, and CLP at an age before and during primary dentition and CLP in mixed dentition age patients using the Mann Whitney U-test (P<0.05). RESULTS: Moderate to abundant numbers of nestin immunoreactive structures were observed in the oral mucosa. CD34 antibodies labeled all microvessels in lamina propria of the CLP affected tissue, while low numbers of TGFβ3 positive cells were scattered in the connective tissue. There were no statistically significant differences between the study groups. CONCLUSION: Expression of nestin in complete unilateral and bilateral cleft lip and palate affected soft tissue indicates a potential increase of tissue regeneration. CD34 positive oral mucosa cells suggest increased angiogenesis, while the sporadic expression of TGFβ3 indicates an insignificant role in the maintenance and growth of cleft affected oral mucosa stem or progenitor cells. Nevertheless, scarce expression of TGFβ3 suggests a role in cleft morphopathogenesis.publishersversionPeer reviewe

Appearance and distribution of tissue remodellation factors in the hard tissue of patients affected by cleft lip palate

Funding Information: This study was funded by Riga Stradins University, No. 5-1/106/2019 from 12.04.2019, “The elaboration of diagnostic prognostic factor algorithm of facial tissue complex regeneration for cleft patients in longitudinal aspect”. Publisher Copyright: © 2020 Sciendo. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Bone repair after surgical intervention on cleft lip palate (CLP) depends on the coordinated action of multiple tissue regeneration factors. We determined the relative number and appearance of tissue factors: matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic protein 2/4 (BMP 2/4), transforming growth factor beta (TGF-ß), Wnt3a protein (Wnt3a), Runt-related transcription factor 2 (Runx2), basic fibroblast growth factor (bFGF) and osteoprotegerin in hard tissue of CLP patients during first time surgical intervention. Fourtythree CLP patients with 24 bone and 36 cartilage samples were involved. Immunohistochemistry was used to assess the levels of tissue factors and the semi-quantitative census method was used for quantification of immunological structures. The increased amount of MMP-2 and bFGF positive cells was detected in the CLP group in cartilage and bone (p < 0.05), compared to the controls. A statistically significant (p = 0.012) increased amount of BMP 2/4 positive cells was found in cartilage of CLP patients, in comparison to the control group. Increased appearance of MMP-2, bFGF in hard tissue of the CLP patients indicates the predominance of tissue degradation. Increased number of BMP2/4 positive chondrocytes suggests improved cartilage growth and better regeneration in CLP patients.publishersversionPeer reviewe

Apoptosis and MMP-2, TIMP-2 expression in cleft lip and palate

Aim of our study was complex detection of appearance and distribution of specific signalling proteins and apoptosis in facial tissue of children with complete bilateral cleft lip and palate (CBCLP). MATERIALS AND METHODS. Nineteen CBCLP patients and 11 unaffected subjects were involved in this study. All the tissue samples were proceeded for detection of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and apoptosis. The intensity of immunostaining was graded semi-quantitatively. Results of the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method were obtained by counting apoptosis positive cells in five unintentionally chosen fields of vision. Groups were compared using the Mann-Whitney test. RESULTS. TUNEL-positive oral epithelial cells were significantly increased in the control group when compared with the CBCLP group. Connective tissue cells have a statistically significant lower expression of TIMP-2 in the control group compared to the CBCLP group. CONCLUSIONS. TIMP-2 positive connective tissue cells increasingly found in oral mucosa lamina propria proves the decrease of local apoptosis in CLP patients. Prominent expression of MMP-2 in cleft affected soft tissue indicates a possible increase of tissue remodelling.publishersversionPeer reviewe

The influence of early orthodontic treatment on the growth of craniofacial complex in deciduous occlusion of unilateral cleft lip and palate patients

This study evaluates dental occlusion and dental arch parameters of 5-6 year old children with unilateral cleft lip and palate (UCLP) treated and untreated orthodonticly before lip plastic with noncleft children. The aim of the study was to verify whether early orthodontic treatment improves deciduous dental arch relationship of children with unilateral cleft lip and palate.135 casts of 5-6 year old children from Riga and Vilnius were evaluated. 90 casts from children with UCLP (45 - got early orthodontic treatment, 45 - without early orthodontic treatment) and 45 casts from noncleft children. All patients with UCLP had surgically closed lip and palate; five-Year-Olds, Index was used to assess dental arch relationship of UCLP patients. Measurements of dental arch length, canine and molar arch width was taken similar to Bland and Altman method. Statistical analysis: the difference of the mean values was tested using t-test between and within groups: UCLP-1 (without early orthodontics), UCLP-2 (treated orthodonticaly before lip plastic) and control group - noncleft children). Measurements were performed by two calibrated orthodontists, mean error was calculated according to the Dalberg method. Measurement error was less than 1 mm. Measurements showed that the occlusion parameters and transverse distance between deciduous molars of UCLP-1 group differed from the occlusion of UCLP-2. Children who had got early orthodontics showed better growth of the maxillae. More cases with positive overjet and meziodistal or distal deciduous molar relationship had treated with early orthodontics. Maxillary width between deciduous molars was statistically significant wider in children with UCLP who had early orthodontic treatment comparing with untreated children. Growth of mandible was not inhibited and did not differ treated and untreated children with UCLP and control group.publishersversionPeer reviewe