Michael Krimmel

Digital Surface Photogrammetry for Anthropometric Analysis of the Cleft Infant Face

Objective To analyze the three-dimensional morphology of the cleft infant face with digital surface photogrammetry. Design Fifty plaster casts of unoperated infants with cleft lip and palate were imaged three-dimensionally with digital surface photogrammetry. Twenty-one standard craniofacial measurements were taken. The plaster casts were divided into 4 groups with unilateral, bilateral, complete, and incomplete clefts of the lip and palate. The measurements were compared with standard values for healthy infants. Results Significant differences (p < .0025) were found for the alar base width (33% to 55%), the alar base root width (59% to 103%), the width of the nose (7% to 25%), the length of the alar wing (18% to 25%), and the intercanthal (6% to 17%) and biocular (4% to 12%) width, depending on the cleft type. The vertical dimensions of the nose and the upper lip did not differ significantly from the controls. Conclusion This study describes preliminary data on the cleft infant facial deformity. The obtained results were mainly in agreement with data in the limited literature. Three-dimensional photogrammetry has proven to be reliable and can be applied more readily to potentially uncooperative patients.

External distraction of the maxilla in patients with craniofacial dysplasia.

Patients with severe maxillary hypoplasia secondary to craniofacial dysplasia present a challenge to the craniofacial surgeon. Maxillary distraction presents a promising tool to treat these patients more successfully. Fifteen patients aged 12 to 20 years with craniofacial dysplasia and maxillary retrusion were treated with two different techniques after complete Le Fort I osteotomy: one group underwent face mask protraction (2 patients), and the other group underwent rigid external distraction (13 patients). Cephalometric evaluation was performed before and after distraction. Rigid external distraction appeared to be superior to face mask protraction. Maxillary retrusion was fully corrected in this group. The path of maxillary positioning was well controlled by changing the traction force vector. Distraction osteogenesis has certainly improved treatment of these patients.

What is the optimal time to start helmet therapy in positional plagiocephaly

Background: Although helmet therapy is widely accepted in the treatment of severe positional plagiocephaly, treatment regimens, especially regarding starting age, are controversial. This study investigated the importance of starting age to optimize the management of helmet therapy. Methods: Sixty-two infants with severe positional plagiocephaly were enrolled in this prospective longitudinal study. Twenty-four started helmet therapy before 6 months of age (group 1) and 38 were older than 6 months (group 2). Cranial diagonal measurements were taken. Resulting differences and Cranial Vault Asymmetry Index values were compared and categorized by age at initiation of therapy. The Mann-Whitney U test was used for statistical analysis. Results: Duration of therapy was significantly shorter in group 1 (14 weeks) compared with group 2 (18 weeks) (p = 0.013), with significantly better outcomes. The Cranial Vault Asymmetry Index in group 1 was reduced to a normal mean value less than 3.5 percent. Infants in group 2 did not achieve normal values (index value, 4.5 percent) (p = 0.021). The relative improvement in asymmetry was significantly better in group 1 (75.3 percent) compared with group 2 (60.6 percent) (p = 0.001). After 4 to 11 weeks of treatment, group 1 already showed a better absolute reduction (p < 0.001) and a better relative reduction (p = 0.002). Conclusions: Optimal starting age for helmet therapy is months 5 to 6 of life, and early recognition of infants in need is essential. Delaying the onset of treatment significantly deteriorates the outcome. The still often-practiced regimen of starting helmet therapy after physiotherapy should be replaced by a combined therapy in severe cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. Figure. No caption available.

ABCB5 expression and cancer stem cell hypothesis in oral squamous cell carcinoma

INTRODUCTION The vast majority of oral cancers are squamous cell carcinomas (OSCC). The effectiveness of adjuvant cytostatic chemotherapy for OSCC is frequently restricted due to an inducible cellular mechanism called multidrug resistance (MDR) and a putative cancer stem cell (CSC) compartment in human carcinogenesis expressing multidrug efflux pumps. The novel human ATP-binding cassette (ABC) transporter ABCB5 [subfamily B (MDR/TAP) member 5] acts as an energy-dependent drug efflux transporter and marks tumour cells of a putative CSC compartment. However, to date, there is no link between ABCB5 expression and OSCC. MATERIALS AND METHODS Expression of ABCB5 was analysed in OSCC specimen (n=191) and cancer cell lines (BICR3, BICR56) by immunohistochemistry, real-time polymerase chain reaction (RT-PCR) analysis and western blotting. Scanned images were digitally analysed using ImageJ and the immunomembrane plug-in. ABCB5 expression on protein level was correlated with clinical characteristics and impact on survival. ABCB5 was co-labelled with CD44 in immunohistochemical and immunofluorescence double labelling experiments. Expression subgroups were identified by receiver operating characteristics (ROC) analysis. RESULTS High ABCB5 expression was significantly associated with tumour progression and recurrence of the tumour. Multivariate analysis demonstrated high ABCB5 expression as an independent prognostic factor (p=0.0004). Immunohistochemical and immunofluorescence double labelling experiments revealed ABCB5 expression by CD44+ cancer cells. ABCB5 specificity was confirmed by western blot and RT-PCR analysis. CONCLUSIONS For the first time, this study provides evidence that ABCB5 expression in OSCC might be associated with tumour formation, metastasis and a putative CSC compartment. One of the principal mechanisms for protecting putative cancer stem cells is through the expression of multifunctional efflux transporters from the ABC gene family, like ABCB5. This provides one mechanism in which putative cancer stem cells could survive and may lead to tumour relapse. Knowledge of expression profiles of ABC transporters and other genes involved in MDR will likely help therapeutic optimisation for cancer patients in clinic. However, this hypothesis requires further in vitro and in vivo studies.

Relevance of SCC-Ag, CEA, CA 19.9 and CA 125 for diagnosis and follow-up in oral cancer

The prognosis of oral cavity carcinoma is limited by recurrent disease or lymph node metastasis. Secondary to surgery and radiotherapy, anatomical structures are often severely changed and make early diagnosis of renewed tumour growth by clinical and radiological examination difficult. We studied the course of serum SCC-Ag, CEA, CA 19.9 and CA 125 in 121 patients with untreated squamous cell carcinoma of the head and neck (SCCHN) before and after therapy and evaluated their relevance for diagnosis and follow-up in oral cancer. CA 19.9 and CA 125 seemed to be useless for this tumour entity. CEA resembled more the alcohol consumption and smoking habits of the patients examined than their state of disease. Only SCC-Ag correlated with the tumour burden and represented the disease course. In the event of relapse, half the patients had an exponential increase in SCC-Ag, 1-2 months prior to diagnosis.

Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin†

Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome‐wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC). The sample included 74 NSCL/P families, 15 NSCPO families, and 2 mixed families (a total of 217 affected and 230 unaffected individuals were genotyped). We genotyped 542 microsatellite markers (average intermarker distance = 6.9 cM). Multipoint nonparametric linkage analysis was performed using Allegro 2.0f. In addition to the factors investigated in previous genome‐wide linkage analyses, we searched for sex‐specific susceptibility loci, loci demonstrating parental imprinting and loci that are shared by NSCL/P and NSCPO. Several genomic regions likely to contain susceptibility loci for NSC were identified at the level of nominal significance. Some of these overlap with regions identified in previous studies. Suggestive evidence of linkage was obtained for the loci 4q21‐q26 and 1p31‐p21, with the chromosome 1 locus showing a male‐specific genetic effect. Our study has identified promising chromosomal regions for the identification of NSC‐associated genes, and demonstrates the importance of performing detailed statistical analyses which take into account complex genetic mechanisms such as sex‐specific effects and genomic imprinting. Further research in large patient samples is necessary to identify factors common to NSCL/P and NSCPO.

Cleft palate fistula closure with a mucosal prelaminated lateral upper arm flap.

Background: Recurrent cleft palate fistula is a challenge for maxillofacial surgeons. In severe cases, microvascular tissue transfer is necessary to treat these patients successfully. Methods: A 23-year-old man with cleft lip and palate, previously treated elsewhere, presented with a 2-cm defect in the posterior hard palate. A tongue flap had already been performed. It was decided to close the persistent fistula with a lateral upper-arm flap. In a first-step operation, a free graft of buccal mucosa was fixed to the lateral upper arm subcutaneously and covered with an alloplastic sheet. After 11 weeks, the prelaminated flap was harvested and transferred to the palate. Results: Integration of the buccal mucosa to the upper arm was uneventful. On harvesting the flap, we found a smooth, thin, and continuous fasciomucosal flap with a mucosa surface of 4 × 4 cm. Healing of the microvascular flap in its recipient site was regular. The fistula was closed successfully. Conclusions: To the authors’ knowledge, this is the first report of a lateral upper-arm flap prelaminated with autologous mucosa. By prelamination, it is possible to circumvent the disadvantage of extraoral skin within the oral cavity and to cover mucosal defects with mucosa, especially in elective procedures, such as cleft cases.

3D histology-guided surgery for basal cell carcinoma and squamous cell carcinoma: recurrence rates and clinical outcome

In a prospective study, a large number of patients with basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) underwent surgery using three dimensional (3D) histology and were evaluated with respect to local recurrence. The excised tumours were treated using 3D-histology with a routine paraffin procedure until the surgical margins were clear of tumour. Prospective evaluation of recurrence-free survival and overall survival of 5227 primary BCCs in 3320 patients and 615 invasive primary SCCs in 600 patients was conducted in the form of a letter-based follow-up with feedback from the patients and the referring physicians. The mean follow-up period was 5 years. In the BCC collective, 36 out of 3320 patients developed local recurrence (1%, calculated as a percentage of treated BCCs: 0.7%). In the SCC collective, 20 local recurrences appeared (3%). The recurrence rate for SCCs with desmoplasia was 24%, whilst the recurrence rate for common types of SCC without desmoplasia was 1%. Surgery followed by 3D histology results in very low recurrence rates for BCC and SCC with no additional effort compared with the normal histopathological procedure.

Facial Surface Changes After Cleft Alveolar Bone Grafting

PURPOSE The aim of this study was to assess the 3-dimensional facial surface changes after cleft alveolar bone grafting with digital surface photogrammetry. PATIENTS AND METHODS In a prospective study, 22 patients with cleft lip and palate underwent alveolar bone grafting. Before the procedure and 6 weeks postoperatively and before the continuation of orthodontic treatment, 3-dimensional images were taken with digital surface photogrammetry. Seven standard craniofacial landmarks on the nose and the upper lip were identified. Their spatial change because of bone grafting was assessed. Statistical analysis was performed with analysis of variance and t test. RESULTS A significant increase in anterior projection on the operative side (P < .05) was found for the labial insertion points of the alar base (subalare). No significant changes were detected for the position of the labial landmarks. CONCLUSION Our results show 3-dimensionally that there is a positive influence of the alveolar bone graft on the projection of the alar base on the cleft side.

Implementing a Superimposition and Measurement Model for 3D Sagittal Analysis of Therapy-induced Changes in Facial Soft Tissue: a Pilot Study

Aim:3D digital surface photogrammetry is an objective means of documenting the quantitative evaluation of facial morphology. However, there are no standardized superimposition and measurement systems for surveying soft tissue changes. The aim of this study was to present a superimposition and measurement model for three-dimensional analysis of therapy-induced sagittal changes in facial soft tissue and to ascertain its applicability based on the reproducibility of 3D landmark positions.Patients and Method:Twenty-nine children were examined (eight with cleft lip and palate, six with cleft palate, eight with Class III malocclusion and seven healthy controls, between 4.1 and 6.4 years). The mean time between examinations was 8.2 months for the patients and 8 months for the control group. Data was acquired with the DSP 400©imaging system. A mathematical model with seven superimposition points was developed. Two 3D images, one at the beginning and the other at the end of the examination, were generated. Both images were superimposed ten times. Ten landmarks for evaluating the soft tissue changes were geometrically defined on the superimposition image, put in place ten times, and measured. The landmarks’ reproducibility was calculated via statistical intraoperator analysis. Measurement error was identified using the root mean square error (RMSE).Results:The superimposition points were easy to locate and the landmarks well definable. All midface landmarks proved to be highly reproducible with an RMSE under 0.50 mm. The lower face landmarks demonstrated good reproducibility with an RMSE under 1 mm. The midface landmarks’ precision fell below the range of accuracy, while the lower face landmarks’ precision fell within the optoelectronic scanner device’s range of accuracy (0.50–1 mm).Conclusions:As an accurate, non-invasive, millisecond-fast, non-ionizing and ad infinitum repeatable procedure, 3D digital surface photogrammetry is very well suited for clinical and scientific application in orthodontics. We developed a reliable superimposition and measurement model with 3D digital surface photogrammetry. This new capturing and measurement system provides a simple means of determining 3D changes in facial soft tissue. Our landmarks proved to be highly reproducible for the midface while revealing good reproducibility for the lower face.ZusammenfassungZiel:Die digitale 3D-Oberflächenphotogrammetrie stellt ein objektives Verfahren dar, um die Gesichtsmorphologie quantitativ zu erfassen. Standardisierte Überlagerungs- und Auswertungsmodelle zur Vermessung von Weichteilveränderungen fehlen jedoch. Ziel dieser Studie war es, ein Überlagerungs- und Auswertungsmodell zur dreidimensionalen Analyse von therapiebedingten sagittalen Gesichtsweichteilveränderungen zu entwickeln und dessen Anwendbarkeit anhand der Reproduzierbarkeit der 3D-Landmarkenpositionierung zu überprüfen.Patienten und Methodik:Es wurden 29 Kinder, acht mit LKGSpalten, sechs mit Gaumenspalten, acht mit Klasse-III-Anomalien und sieben gesunden Kontrollen, zwischen 4,1 und 6,4 Jahren untersucht. Das Untersuchungsintervall betrug 8,2 Monate für die Patienten und 8 Monate für die Kontrolle. Die Datenakquisition erfolgte mit dem DSP-400©-System. Es wurde eine mathematische Konstruktion mit sieben Überlagerungspunkten entwickelt. Zwei 3D-Bilder, zum Untersuchungsbeginn und Untersuchungsende, wurden generiert und zehnfach überlagert. Auf dem Überlagerungssummenbild wurden zehn Messpunkte zur Erfassung der Weichgewebeveränderungen geometrisch bestimmt, zehnfach platziert und vermessen. Die Reproduzierbarkeit der Messpunkte wurde mit einer statistischen Intraoperatoranalyse überprüft. Der Messfehler wurde mit dem „Root Mean Square Error“ (RMSE) berechnet.Ergebnisse:Die Überlagerungspunkte ließen sich gut auffinden und die Messpunkte im Anschluss gut definieren. Alle Mittelgesichtspunkte zeigten eine hohe Reproduzierbarkeit mit einem RMSE kleiner als 0,50 mm. Die Untergesichtspunkte waren mit einem RMSE kleiner als 1 mm gut reproduzierbar. Die ermittelte Präzision der Mittelgesichtspunkte lag somit unterhalb und die der Untergesichtspunkte innerhalb der Genauigkeit des optoelektronischen Scanners (0,50–1 mm).Schlussfolgerungen:Als genaues, nichtinvasives, millisekundenschnelles, strahlenfreies und ad infinitum wiederholbares Verfahren ist die digitale 3D-Oberflächenphotogrammetrie sehr gut für den klinischen und wissenschaftlichen Einsatz in der Kieferorthopädie geeignet. Ein zuverlässiges Überlagerungs- und Auswertungssystem konnte mit der angewandten digitalen 3D-Oberflächenphotogrammetrie eingeführt werden. Es handelt sich um eine einfache Methode, faziale Weichteilveränderungen zu ermitteln. Die Messpunkte zeigten eine hohe (Mittelgesichtsbereich) bis gute (Untergesichtsbereich) Reproduzierbarkeit.