Current concepts in cleft care: A multicenter analysis.

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery.

Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample.

BACKGROUND: Nonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci. METHODS: We genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family-based sample of European ancestry (n = 212); and (ii) two case/control samples of Central European (n = 94/339) and Arabian ancestry (n = 38/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta-analyses were performed. RESULTS: After association analysis and meta-analyses, none of the 33 SNPs showed genome-wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in p-value in a European and an overall meta-analysis including imputed GWAS data, respectively (rs395572: PMetaEU = 3.16 × 10-4 ; rs6809420: PMetaAll = 2.80 × 10-4 ). CONCLUSION: Our findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL/P, for which GWAS of smaller sample sizes have identified genome-wide significant loci. Whole-exome/genome sequencing studies of nsCPO are now warranted.

Moving the mandible in orthognathic surgery - A multicenter analysis.

Orthognathic surgery has always been a classical focus of maxillofacial surgery. Since more than 100 years, various surgical techniques for mandibular repositioning have been developed and clinically tested. Since the establishment of plate and screw osteosynthesis, orthognathic surgery became more stable and safe. Nowadays, different surgical methods for mobilising the mandible are existing. This international multicenter analysis (n = 51 hospitals) is providing first evidence based data for the current use of different surgical methods. The dominating techniques were Obwegeser/dal Pont (61%) followed by Hunsuck/Epker (37%) and Perthes/Schlössmann (29%). The main osteosynthesis materials were plates (82%), bicortical screws (23.5%), or a combination of both (5.9%). 47% of all centers reported to use several surgical methods at the same time, depending on the anatomical problem and the surgeon's preference. This shows that different surgical methods seem to work as comparable, safe, and reliable procedures in everydays clinical practise. On this basis, further prospective studies could evaluate possible advantages for our patients.

The current state of facial prosthetics ­ A multicenter analysis.

Even though modern surgical techniques are dominating reconstructive facial procedures, the capability to use facial epitheses for reconstruction is still an important skill for the maxillofacial surgeon. We present an international multicenter analysis to clarify which techniques are used to fixate facial prostheses. We contacted all maxillofacial departments in Germany, Austria, Switzerland and Norway which were registered with the German society for oral and maxillofacial surgery (DGMKG). These centers were asked via electronical mail to provide information on the type of epithesis fixation systems currently in use. The return rate from 58 departments was 43.1% (n = 25). Overall, implant fixation was the preferred fixation system (92%). Plates were the second most common fixation technique (32%). No centers reported the standard use of non-invasive fixation techniques for permanent epithesis fixation. The main retention systems in use were magnets (24/25), other retention systems are used much less often. The current preferred fixation technique for facial epitheses consists of implant-based, magnet-fixated epitheses. For nasal prostheses, a plate-based, magnet-fixated system is often used.

Cowpox virus outbreak in banded mongooses (Mungos mungo) and jaguarundis (Herpailurus yagouaroundi) with a time-delayed infection to humans.

BACKGROUND: Often described as an extremely rare zoonosis, cowpox virus (CPXV) infections are on the increase in Germany. CPXV is rodent-borne with a broad host range and contains the largest and most complete genome of all poxviruses, including parts with high homology to variola virus (smallpox). So far, most CPXV cases have occurred individually in unvaccinated animals and humans and were caused by genetically distinguishable virus strains. METHODOLOGY/PRINCIPAL FINDINGS: Generalized CPXV infections in banded mongooses (Mungos mungo) and jaguarundis (Herpailurus yagouaroundi) at a Zoological Garden were observed with a prevalence of the affected animal group of 100% and a mortality of 30%. A subsequent serological investigation of other exotic animal species provided evidence of subclinical cases before the onset of the outbreak. Moreover, a time-delayed human cowpox virus infection caused by the identical virus strain occurred in a different geographical area indicating that handling/feeding food rats might be the common source of infection. CONCLUSIONS/SIGNIFICANCE: Reports on the increased zoonotic transmission of orthopoxviruses have renewed interest in understanding interactions between these viruses and their hosts. The list of animals known to be susceptible to CPXV is still growing. Thus, the likely existence of unknown CPXV hosts and their distribution may present a risk for other exotic animals but also for the general public, as was shown in this outbreak. Animal breeders and suppliers of food rats represent potential multipliers and distributors of CPXV, in the context of increasingly pan-European trading. Taking the cessation of vaccination against smallpox into account, this situation contributes to the increased incidence of CPXV infections in man, particularly in younger age groups, with more complicated courses of clinical infections.

Transforming growth factor-beta receptor type 1 (TGFBR1) is not associated with non-syndromic cleft lip with or without cleft palate in patients of Central European descent.

OBJECTIVE: Transforming growth factor-beta (TGF-ß) type 1 receptor (also known as activin receptor-like kinase 5, ALK5) is expressed in palatal tissue during embryogenesis. Experimental studies in transgenic mice with a genetic deletion of Alk5 showed that TGF-ß type 1 receptor is required for upper lip and midline fusion of the hard and soft palate. In humans, association of TGF-ß type 1 receptor gene (TGFBR1) and the development of non-syndromic cleft lip with or without cleft palate (NSCL/P) had been observed in a multiethnic sample of Chinese, Philippine, Indian and Turkish families. In order to re-evaluate the relevance of these findings, we carried out a family-based association study among 218 NSCL/P families of Central European descent. METHODS: Genomic DNA was obtained from peripheral blood of 218 complete parent-offspring triads with NSCL/P. The sample comprised 14 patients with cleft lip only (CLO) and 204 patients with cleft lip and palate (CLP). Genotyping and transmission disequilibrium test (TDT) were performed on all 218 triads with a total of 17 tagging single-nucleotide polymorphisms (SNPs). We also performed testing for extended haplotypes and a log-linear model by Weinberg was used to screen parent-of-origin effects. Furthermore the use of estimates for the relative risks (RR) of Weinberg's model was obtained. RESULTS: TDT analysis revealed no significant transmission distortion, neither at the level of individual markers nor at the level of haplotypes. Similarly negative results were obtained when we restricted our analysis to the subgroup of patients with CLP (n=204). Relative risk calculations (RR) of the children's and mothers' genotypes obtained negative results, after correction of p-values for multiple testing. Likewise application of Weinberg's log-linear model did not find any evidence for parent-of-origin effects in our sample. CONCLUSION: Despite the ample evidence supporting the role of TGF-ß type 1 receptor as a critically important and widespread morphogenetic regulator of craniofacial development in murine models, our results do not support TGFBR1 as major risk factor for NSCL/P in patients of Central European descent.

Reconstruction of the lower lip: rationale to preserve the aesthetic units of the face.

BACKGROUND: The boundaries of the aesthetic units of the face are often crossed after lower lip cancer surgery. The aim of this study was to compare the aesthetic and functional outcome after use of different operative techniques based on the concept of the aesthetic units of the face. MATERIALS: Sixty-three patients were evaluated after lower lip reconstruction. The aesthetic outcome was recorded by standard photography evaluating the disruption of the boundaries of the aesthetic units of the face, lip projection, and the resulting facial expression. The functional outcome consisted of the evaluation of mouth opening, pouting, and lips at rest for the evaluation of mouth continence. Three techniques were used: wedge excision, the Webster-Fries method, and the step technique. The step technique was combined with an Abbé or an Estlander flap in defects involving more than two-thirds of the lip. RESULTS: In defects involving up to one-third of the lip, the aesthetic outcome was better for the step technique than for wedge excision (a statistical trend was observed, p = 0.088). In defects involving two-thirds of the lip, the aesthetic and functional outcome was better using the step technique than the Webster-Fries method (p = 0.002), because the boundaries of the aesthetic units are respected. In defects involving more than two-thirds of the lip, the result was better using the step technique combined with the Abbé flap. CONCLUSION: The authors have shown that the step technique alone or combined with a flap of the opposite lip is a rational approach for preserving the aesthetic units of the face and its function.

One- or two-stage palate closure in patients with unilateral cleft lip and palate: comparing cephalometric and occlusal outcomes.

OBJECTIVE: To assess facial growth and dentoalveolar development in two groups of patients with complete unilateral cleft lip and palate. Primary surgical treatment differed in the timing of hard palate closure. DESIGN: Forty-three patients with unilateral cleft lip and palate were examined. Twenty-two patients underwent early one-stage closure of the hard and soft palate cleft (mean age 23.0 +/- 4.7 months); in 21 patients, the hard palate closure was delayed to 86.3 +/- 39.2 months of age. Lateral cephalograms and dental casts were consecutively analyzed at four stages between 6 and 18 years of age. RESULTS: Lateral cephalometric analysis revealed no significant intergroup differences in the sagittal and vertical craniofacial dimensions at any time. Dental cast analysis showed constriction of the upper anterior arch width at the ages of 6 and 10 years in patients with one-stage surgical palate closure, but a difference could no longer be verified at the ages of 15 and 18 years. CONCLUSIONS: The transverse distances in the upper jaw developed initially more positively in the group with delayed hard palate closure, but it became apparent later that the transverse deficiency after one-stage palate closure could be compensated for. When considering surgical treatment in general, the advantages of the delayed hard palate closure must be weighed against criteria favoring the early one-stage closure of the hard and soft palate.

Dentigerous cyst versus unicystic ameloblastoma--differential diagnosis in routine histology.

BACKGROUND: Unicystic ameloblastomas (UAs) and dentigerous cysts (DCs) have an identical clinical and radiographic appearance. Some subtypes of UAs have a better prognosis than solid or multicystic ameloblastomas, and simple enucleation is the adequate treatment. The present study was designed to test the hypothesis that UAs with small islands of ameloblastomatous epithelium may be misdiagnosed as a DC or keratocyst if no more than two histologic sections are examined. METHODS: A total of 101 resection specimens from 22 women and 73 men (mean age: 46.5 years) were selected, all showing the clinical and radiographic features of a DC. Only cysts with a minimum diameter of 15 mm in the panoramic X-ray were considered for the present investigation. The histopathologic diagnosis had been routinely established by examining two sections. For our study, the specimens were investigated by step sections at 50 microm and by staining of 5 microm thin sections with hematoxylin and eosin (H&E) at 1 mm levels. An average of 15 slides were evaluated per case. RESULTS: Microscopic examination of the step sections did not reveal ameloblastomatous epithelium in the cyst lining epithelium of the 101 cases. Thus, every primary diagnosis of a dentigerous cyst was confirmed. In four cases, additional rather large odentogenic cell nests were detected with palisading of basaloid cells, while there was a lack of other signs of ameloblastic differentiation. All lesions were completely resected, and no additional treatment was performed. CONCLUSIONS: Step sectioning of larger DCs may reveal associated odontogenic cell nests in some cases but does not lead to the detection of formerly missed ameloblastic cells. Thus, unicystic ameloblastomas are not misdiagnosed if only two slides are prepared for routine diagnosis of DCs.

Cerebriform giant melanocytic nevus of the scalp: report of two cases with different surgical approaches.

Cerebriform giant melanocytic nevus of the scalp is an extremely rare malformation. Clinical appearance with maceration and fetor within the crypts and the risk of malignant transformation may require surgical therapy. We report two cases with different methods of surgical management. A 27-year-old woman noticed a swelling of the parietal scalp that developed over a period of 4 years into a gyrus-like tumor measuring 12 cm x 18 cm. The crypts between the gyri could not be inspected. Serial excisions under subcutaneous infusion anesthesia were performed to reduce the size of the nevus and to flatten the surface of the scalp. The second patient, a 26-year-old man, demonstrated a giant 10 cm x 10 cm cerebriform nevus on the occiput. The nevus also contained areas of fetid maceration. After implanting a tissue expander under general anesthesia the nevus was excised. The defect was closed using a rotation flap.

The novel human beta-defensin-3 is widely expressed in oral tissues.

The purpose of this study was to investigate the expression of human beta-defensins (hBD), especially of the recently discovered hBD-3, in oral tissues by reverse-transcription polymerase chain reaction (RT-PCR). Primary oral keratinocytes (n = 3) and fibroblasts (n = 3), 64 non-inflamed and 40 inflamed oral tissue samples, and 10 samples of salivary glands, were examined. The transcripts for hBD-3 (61/64), as well as for hBD-1 (64/64) and hBD-2 (54/64), were found to be widely expressed in non-inflamed oral tissues. In contrast, only 23, 22 and 24 of the 40 inflamed tissues showed detectable hBD-1, -2 and -3 transcripts, respectively. In salivary glands, mRNA expression was constitutive for hBD-1, frequent for hBD-2 (9/10), and infrequent for hBD-3 (4/10). Oral keratinocytes, but not fibroblasts, contained transcripts for all beta-defensins, suggesting that the novel hBD-3 is also produced in the epithelial compartment of oral tissues. The results indicate an important role for the novel hBD-3, as well as for hBD-1 and hBD-2, in the innate oral epithelial host defense.