Morphometric Assessment of Facial Morphology in Infants with Orofacial Clefts up to two Years of Age: A Three-Dimensional Cross-Sectional Study.

OBJECTIVE: To assess modelled facial development of infants with unilateral cleft lip (CL) and cleft lip and palate (UCLP) compared to controls up to two years of age. DESIGN AND PARTICIPANTS: A total of 209 facial images of children (CL: n = 37; UCLP: n = 39; controls: n = 137) were obtained in four age categories (T0 = 0.2-0.5; T1 = 0.6-1.0; T2 = 1.1-1.5; T3 = 1.6-2.0 years) and were evaluated using stereophotogrammetry and geometric morphometry. All patients underwent lip surgery before T0, patients with UCLP underwent palatoplasty (T0, T1 before palatoplasty; T2, T3 after palatoplasty). RESULTS: In patients with CL, the forehead was significantly retracted (p ≤ 0.001), while the supraorbital and ocular regions were prominent (p ≤ 0.001). The oronasal region appeared convex (p ≤ 0.001). The lower lip and chin were non-significantly protruded. In patients with UCLP, a significantly retracted forehead and prominent supraorbital region were apparent (p ≤ 0.001). A retrusive oronasal region (p ≤ 0.001) was observed in the middle face. The chin was anteriorly protruded (p ≤ 0.01). No progression of deviations was found with increasing age. After the first year, a slight improvement in the morphological features became apparent. The shape variability of the clefts and controls overlapped, suggesting a comparable modelled facial development. CONCLUSIONS: The facial morphology of individuals with cleft was comparable to the norm. Shape deviation was apparent in the oronasal region, forehead, and chin, which minimised with increasing age even in complete clefts.

Palatal growth changes in newborns with unilateral and bilateral cleft lip and palate from birth until 12 months after early neonatal cheiloplasty using morphometric assessment.

OBJECTIVES: To compare palatal growth changes in infants with complete unilateral (UCLP) or bilateral (BCLP) cleft lip and palate during the first year of life. MATERIALS AND METHODS: Upper dental arches of 68 neonates with UCLP and BCLP were evaluated using 2D and 3D morphometry based on dental casts obtained in two age categories (T0 before early neonatal cheiloplasty-UCLP 4 ± 3 days, BCLP 6 ± 5 days; T1 before palatoplasty-UCLP 10 ± 2 months, BCLP 12 ± 3 months). RESULTS: Intensive palatal growth was manifested in both directions of the palate. Palatal growth in the anterior direction was not restricted, despite the intercanine (CC´) and anterior (LL´) widths being significantly narrowed in the BCLP group (CC´ p = 0.019, LL´ p = 0.009). The posterior dental arches were significantly enlarged (UCLP p ≤ 0.001; BCLP p ≤ 0.001). The negative effect of cleft severity on palatal length was not confirmed (p = 0.802). Variability of the palate was immense mainly in BCLP infants (T0); however, it decreased in both cleft types, confirming the formative effect of palatal growth leading to alveolar cleft closure (UCLP p ≤ 0.001; BCLP p = 0.006 on the right, 0.005 on the left). CONCLUSIONS: Both analyzed cleft groups (UCLP, BCLP) grew favorably during the first year of life, and the palatal growth was not limited in any direction. CLINICAL RELEVANCE: Geometric morphometry allowed a comprehensive analysis of the palate, which can contribute to the improvement of surgical methods.

Duration of Surgery, Ventilation, and Length of Hospital Stay Do Not Affect Breastfeeding in Newborns After Early Cleft Lip Repair.

OBJECTIVE: There are minimal data available on nutrition after early repair of cleft lip and the factors influencing initiation of breastfeeding. This study assessed the impact of the length of surgery, length of ventilation support, and duration of hospital stay on breastfeeding rates after early cleft lip surgery. DESIGN: This is a prospective observational cohort study comparing 2 hospitals providing early surgical repair of facial clefts from January 2014 to December 2016. Both hospitals are designated as Baby-Friendly Hospitals. Demographic and anthropometric data from mothers and newborns were recorded. SETTING: Tertiary neonatal and pediatric surgery center. PATIENTS: Hospital A: 61 newborns, Hospital B: 157 newborns. INTERVENTIONS: Early (day 5 to 14) cheiloplasty in newborns with cleft lip or cleft lip and palate. MAIN OUTCOME MEASURES: Influence of duration of hospital stay, length of operation, and artificial ventilation on the rate of breastfeeding. RESULTS: Significantly, more newborns were breastfed following early surgical repair of an isolated cleft lip compared to those with both cleft lip and palate, in both hospitals (hospital A 82% vs 0%, P = .0001, hospital B 66% vs 5%, P = .0001). Duration of hospital stay, length of operation, and duration of artificial ventilation did not significantly affect the rate of breastfeeding. CONCLUSIONS: The factors associated with early cleft lip repair (length of operation, length of ventilation support, and duration of hospital stay) do not affect breastfeeding rate.

Three-dimensional development of the palate in bilateral orofacial cleft newborns 1 year after early neonatal cheiloplasty: Classic and geometric morphometric evaluation.

OBJECTIVES: The aim of this study was to assess palatal growth in newborns with complete bilateral cleft lip and palate (cBCLP) and bilateral cleft lip and palate with tissue bridges (BCLP + B) 1 year after early neonatal cheiloplasty (ENC). MATERIAL AND METHODS: The methodology was based on classic and morphometric analysis of dental models of newborns with cBCLP or BCLP + B. These analyses included metric analysis, coherent point drift-dense correspondence analysis, superprojection methods, and multivariate statistics. Dental casts were observed in two age categories, which were compared with each other. The first cast was obtained from each patient before ENC (T0, 5 ± 5 days) and the second one prior to palatoplasty (T1, 12 ± 6 months). RESULTS: Fifty-two dental models obtained from 26 newborns with cBCLP and BCLP + B were evaluated. The results showed that over the 12-month period, alveolar clefts were narrowed in both cleft types due to anterior growth combined with the formative effect of suturing. This was confirmed by decreases in the dimensions of the right (T0 9.93 ± 2.80 mm, T1 6.64 ± 2.43 mm; p ≤ 0.003) and left (T0 10.71 ± 4.13 mm, T1 6.69 ± 4.29 mm; p ≤ 0.003) alveolar clefts in cBCLP patients. Similar reductions in alveolar cleft widths occurred on the left side (T0 11.69 ± 4.75 mm, T1 4.34 ± 2.97 mm; p ≤ 0.001) of BCLP + B patients, while on the right side, which was connected by a combined tissue bridge, there was non-significant narrowing of the alveolar cleft (T0 1.61 ± 1.34 mm, T1 1.04 ± 0.70 mm; p = 0.120). The ENC did not restrict posterior palatal growth, meaning that intertuberosity width was extended in cBCLP (T0 32.80 ± 3.15 mm, T1 35.86 ± 2.80 mm; p ≤ 0.001) and in BCLP + B neonates (T0 34.01 ± 2.15 mm, T1 36.21 ± 2.14 mm; p ≤ 0.004). Width and length measurements in the observed groups showed growth tendencies equivalent to those in noncleft or LOP patients. Palatal variability was greater in neonatal cBCLP, but was reduced during the monitored period, approximating that for BCLP + B. Regions with the most notable palatal growth were located primarily at the premaxilla and at the anterior and partially posterior ends of the maxillary segments. CONCLUSION: Early neonatal cheiloplasty had no negative effect on palatal growth in any direction. There was no reduction in the length or width of the palate during the first year of life, nor was there narrowing of the dentoalveolar arch. The formative effect of the operated lip on the anterior part of the palate was confirmed. This, in combination with the favorable growth, lead to closure of the alveolar cleft.

Three-dimensional assessment of facial asymmetry in preschool patients with orofacial clefts after neonatal cheiloplasty.

OBJECTIVES: To evaluate facial asymmetry changes in pre-school patients with orofacial clefts after neonatal cheiloplasty and to compare facial asymmetry with age-matched healthy controls. METHODS AND MATERIALS: The sample consisted of patients with unilateral cleft lip (UCL), unilateral cleft lip and palate (UCLP), and bilateral cleft lip and palate (BCLP). The patients were divided in two age groups with a mean age of 3 years (n = 51) and 4.5 years (n = 45), respectively, and 78 age-matched individuals as controls. Three-dimensional (3D) facial scans were analyzed using geometric morphometry and multivariate statistics. RESULTS: Geometric morphometry showed positive deviations from perfect symmetry on the right side of the forehead in the intervention groups and the controls. The UCL groups showed the greatest asymmetric nasolabial area on the cleft-side labia and the contralateral nasal tip. The UCLP group showed, moreover, asymmetry in buccal region due to typical maxillar hypoplasia, which was accentuated in the older group. The BCLP groups showed slightly similar but greater asymmetry than the control groups, except for the philtrum region. CONCLUSIONS: Asymmetry of each of the cleft groups significantly differed from the controls. Except for the buccal region in the UCLP and BCLP groups, asymmetry did not significantly increase with age.

Treatment of gynecological cancers diagnosed during pregnancy.

Because of a notable increase in age at delivery, the incidence of malignancy diagnosed during pregnancy has substantially increased. This review aims to summarize the literature and expert knowledge on gynecologic cancers diagnosed in pregnancy regarding epidemiology, examination and staging procedures, description of treatment modalities and management of gynecological malignancies with special interest in cervical and ovarian cancer. Thorough attention is paid to the surgery and chemotherapy administration for early-stage cervical cancer diagnosed during pregnancy.

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.