Retrospective cohort study of three-wall orbital resection for treatment of endocrine orbitopathy using 3D tomographic data and biomechanical modeling.

BACKGROUND: Surgical treatment of endocrine orbitopathy can be performed by way of resecting orbital walls, which effectively releases superfluous tissue from the surgically enlarged orbital space allowing the eyeballs to move back. Existing approaches aim to select an optimal surgical strategy based on statistical correlations between the extent of the surgical procedure and the resulting bulbus displacement but do not provide an individual surgery plan or predict surgery outcome. METHODS: In this retrospective study, we performed a quantitative analysis of pre- and post-surgery 3D tomographic data of six patients and applied explorative biomechanical modeling of orbital mechanics to dissect factors influencing patient-specific outcome. FINDINGS: Our experimental results showed a large variability of the backward eyeball displacement in dependency on the amount of orbital volume flow, which could partially be described by computational simulation. Our detailed analysis revealed that patients with regular fat tissue show a good correlation between bulbus displacement and relative volume of decompressed tissue, which, in turn, correlates with decrease in hydrostatic pressure. In contrast, patients with fibrotic tissue exhibit significantly reduced and computationally less predictable eyeball translation in response to surgical tissue decompression. INTERPRETATION: Based on the results of this study we see a great potential for quantitative planning of surgical exophthalmos treatment using 3D biomechanical modeling. Conventional approaches to planning of soft tissue interventions consider, however, only the patient's 3D anatomy and widely disregard individual tissue properties. Further investigations are required to establish reliable procedures for assessment of individual tissue properties and incorporating them into patient-specific models of orbital mechanics.

Usage characteristics and adverse event rates ​of the direct puncture and pull techniques for percutaneous endoscopic gastrostomy in patients with malignant tumors of the upper aerodigestive tract.

BACKGROUND AND STUDY AIMS: Patients with malignant tumors of the upper gastrointestinal tract are at risk of weight loss. Early supportive nutrition therapy is therefore recommended and usually requires placement of a percutaneous endoscopic gastrostomy (PEG). The aim of this study was to compare adverse events and usage characteristics of the direct puncture technique with those of the traditional pull technique when used in patients with endoscopically passable tumors. The primary endpoint was the rate of inflammatory adverse events (AEs) at the gastrostomy fistula. The secondary endpoint was the long-term rate of puncture-site metastases. PATIENTS AND METHODS: One hundred twenty patients (median age 56; IQR 36, 86 years) were randomized and treated per protocol in this prospective open randomized single-center study. Follow-ups were conducted on the third and seventh post-interventional days, after 1, 3 and 6 months and the last follow-up 5 years after intervention. RESULTS: Within the short-term follow-up period of 6 months after PEG placement, AEs were noted in 47 patients (39.2 %). These included 22 inflammations and 16 device dislocations and were mainly found in the puncture group (33 vs. 14 in the pull group) with a significantly increased incidence in the first month after PEG insertion ( P  = 0.001). Evaluation of the 5-year data did not reveal any significant differences. The gastrostomy tube was used in 101 patients (84.2 %) (range 18 days to 5 years). CONCLUSIONS: Our results favor the pull technique for patients with endoscopically passable tumors of the upper gastrointestinal tract due to less short-term adverse events. Both systems contributed equally to secure long-term use.

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate.

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10(-2)). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10(-5); ORallelic = 2.46 [95% CI 1.6-3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10(-9)). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO.

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 role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.

Dependence of columella development on the technique used for primary cleft lip closure.

OBJECTIVE: Primary cleft lip closure can be achieved by use of different types of surgery. The procedures of Millard, Veau, and Delaire are among the techniques most frequently performed worldwide. The factors which affect development of the columella have not been studied, however. SETTING: University Hospital of Leipzig, Germany, Department of Oral, Craniomaxillofacial and Facial Plastic Surgery. PATIENTS, PARTICIPANTS: In a comparative, retrospective, non-randomised study, we obtained anthropometric details from photographs of 120 unilateral and bilateral cleft patients after cleft lip closure by use of the techniques of Millard or Veau (n = 60) and Delaire (n = 60). Length and shape of the columella was assessed twice-first at the age of 10 months and again at the age of 10 years. Anthropometric characteristics of columella morphology and development were compared between the two groups. RESULTS: At the age of 10 months, the ratio of nasal height to width (interalar distance) was significantly different for unilateral and bilateral cases, and results were better for the Delaire groups (p = 0.001 unilateral and p > 0.001 bilateral). This effect was no longer apparent at 10-year follow up. Another index which tended to indicate better results in the Delaire groups was the nasal width index. In the summary of the anthropometric values investigated, however, differences between the Millard or Veau group and the Delaire group were marginal. CONCLUSION: Cleft lip closure by the technique of Millard for unilateral cleft lips and of Veau for bilateral cases is neither better nor worse than Delaire cheiloplasty for unilateral and bilateral clefts.

Biomechanical investigation of naso-orbitoethmoid trauma by finite element analysis.

Naso-orbitoethmoid fractures account for 5% of all facial fractures. We used data derived from a white 34-year-old man to make a transient dynamic finite element model, which consisted of about 740 000 elements, to simulate fist-like impacts to this anatomically complex area. Finite element analysis showed a pattern of von Mises stresses beyond the yield criterion of bone that corresponded with fractures commonly seen clinically. Finite element models can be used to simulate injuries to the human skull, and provide information about the pathogenesis of different types of fracture.

Panel perception of facial appearance of cleft patients generated by use of a morphing technique.

OBJECTIVE: Perception of the facial appearance of cleft patients has, until now, been evaluated on the basis of photographs of the patients. Research based on photographs generated by use of a morphing technique has not yet been reported. The purpose of this study was to investigate female and male raters' panel perception with regard to the following: (1) patient age, (2) attractiveness, (3) gender appearance, and (4) likeability of faces of cleft patients generated by the use of a morphing technique. SETTING: The study was conducted at the Department of Oral, Craniomaxillofacial and Facial Plastic Surgery, University Hospital of Leipzig, Germany. PATIENTS, PARTICIPANTS: We used photographs of 32 adult German nonsyndromic cleft patients, mean age 18.9 ± 1.3 years, and surveyed 93 students, mean age 25.3 ± 3.2 years, by use of a standardized questionnaire. RESULTS: All respondents rated the mean age of cleft patients equally in unmorphed and morphed pictures. For all respondents, attractiveness of morphed patient pictures was rated significantly higher than for unmorphed pictures (mean 4.8 ± 1.0 vs. 6.4 ± 2.4; p < 0.001), although significance was reached only if morphed pictures of eight patients were rated. Female respondents rated attractiveness significantly higher than did males, especially for pictures of female patients. CONCLUSION: Facial morphing of patient pictures is a suitable method for creation of standard cleft faces. Despite the modification of the pictures, the faces generated remain human and assessable by panel members. Perception of faces of cleft patients' depended on raters' gender.

Principles of oral surgery for prevention of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: Principles and workflow are described to prevent bisphosphonate-related osteonecrosis of the jaw (BRONJ) when oral surgery is necessary in patients taking bisphosphonates. MATERIAL AND METHOD: A total of 117 surgical procedures were performed on 68 patients taking bisphosphonates. The basis of the treatment was (1) use of perioperative antibiotics; (2) after dentoalveolar surgical procedures, bone edges were smoothed and mucoperiosteal flaps were prepared to ensure tension-free wound closure; (3) sutures were not removed until 14 days postsurgery; (4) long-term results were evaluated. RESULTS: Ninety-seven percent of all procedures were simple and showed no complications. Only 3 patients with a long history of intravenous bisphosphonate medication developed BRONJ within 4 weeks after surgery. No patient receiving oral bisphosphonates developed BRONJ. No long-term failure was observed when primary wound healing was successful. CONCLUSIONS: The high success rate of the described surgical procedures imply dentoalveolar surgery with low risk of development of BRONJ is possible for patients taking bisphosphonates.

Biomechanical mechanisms of orbital wall fractures - a transient finite element analysis.

As the biomechanical mechanisms of orbital wall fractures are still under research, three different fracture mechanisms were tested in a finite element based investigation. In contrast to earlier studies, a finer skeletal model and a transient dynamic simulation were used to test pure hydraulic, pure buckling and a mixed force transmission. Results showed that each set-up led to different orbital fracture patterns, which correlate well with clinical findings. Therefore the conclusion is that different mechanisms may act together explaining the variety of clinical fracture situations. Biomechanical testing has proven to be appropriate in answering questions regarding fracture mechanisms.

Prevalence of cone beam computed tomography imaging findings according to the clinical stage of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: Investigations of cone beam computed tomography (CBCT) for bisphosphonate-related osteonecrosis of the jaw (BRONJ) imaging are rare. The purpose of this study was to investigate the prevalence of typical radiological findings of BRONJ in CBCT. METHODS: Twenty-seven CBCTs of BRONJ sites were assessed on the basis of the radiological findings (cancellous bone destruction, cortical bone erosion, sequestration, osteosclerosis, and periostal bone formation) and put in relation to the severity of the BRONJ sites. RESULTS: Cancellous bone destruction and cortical bone erosion were the most common findings. Occurrence seems to decrease with decreasing BRONJ severity. Sequestration and osteosclerosis were less frequent and could be seen across all stages. Periosteal bone formation occurred in high-stage BRONJ only. CONCLUSION: Cancellous bone destruction, cortical bone erosion, sequestration, and osteosclerosis can be seen across all stages and prevalence seems to decrease with decreasing severity of BRONJ. The occurrence of periosteal new bone formation seems to start in high-stage BRONJ.

Intracranial extension of Schneiderian inverted papilloma: a case report and literature review.

Inverted papilloma is an uncommon primary nasal tumor. Despite its benign nature, this tumor represents three typical characteristics: a high propensity of recurrence, local aggressiveness and association with malignancy. Inverted papilloma can reduce the patient's quality of life due to compromised nasal function, extension to the orbit and brain. The authors reported the unusual case of a 72-year-old male patient with inverted papilloma, which fatally extended to the intracranial temporal fossa after multiple recurrences. To the authors' knowledge, this is the twelfth case in the literature of inverted papilla extending into the temporal fossa. The current and pertinent literature in English, French and German was reviewed, and an algorithm for managing inverted papilloma was also proposed.

German animal terms for oral cleft deformity: a Leipzig survey.

BACKGROUND: German animal terms have been used to name oral cleft deformity for centuries. However, their contemporary use and influence on cleft patients remain unstudied. OBJECTIVE: The main aim of this study was to evaluate the current use of German animal terms for oral cleft and their influence on the perception of cleft patients. METHODS: We used a cross-sectional study design and the study sample consisted of German adult cleft and noncleft subjects in Leipzig, Germany. The study was conducted during May and December 2008, using two questionnaires and two cleft photographs (one unilateral and one bilateral). The predictor variables were medical background and presence of oral cleft. The primary outcome variable was the terminology used for the deformity by noncleft subjects. The secondary outcome variables were self-perception of the cleft patients and their idea about the use of the animal terms. Other study variables included age, gender and specialty/future career of the noncleft participants. Appropriate descriptive, uni- and bivariate statistics were computed, and a P-value of <0.05 was considered to be statistically significant. RESULTS: The study sample was composed of 261 noncleft (146 females [55.9%]) and 71 cleft subjects (33 females [46.5%]) with a mean age of 24.2 ± 6.4 and 24.9 ± 7.2 years, respectively. Noncleft subjects without medical background who used animal terms to name oral cleft deformity were more than those with medical background (P<0.0001). Over half of cleft patients (60.6%) rejected public use of the animal terms, which was still common in their daily life (P<0.0001). CONCLUSIONS: The study results suggest that animal terms have been used until now, especially by those without medical background. The cleft patients become insulted by these negative descriptions. This strikes the importance of public education to replace these animal terms with inoffensive words.

The saxon bisphosphonate register - therapy and prevention of bisphosphonate-related osteonecrosis of the jaws.

In 2009, a study group of three Saxon hospitals set up a Saxon register with the aim of including all patients with bisphosphonate (BP) medication. In addition, specific concepts for surgical approach were developed. The target is to define relevant treatment and prevention strategies of bisphosphonate-related osteonecrosis of the jaws (BRONJ) based on high patient population statistics. Since July 2009, all patients with oral or intravenous BP medication have been registered in the 3 Saxon hospitals. Data was systematically acquired in detailed forms. Totally, 258 patients (♂: 83, ♀: 175) were registered by October 2010. 100 patients out of this already had BRONJ which preferably affected the mandible (70%) and was mostly associated with intravenous medication. In 54 cases, treatment was carried out by surgery according to the strategy developed. The criterion for success was absence of symptoms at least for 3 months after surgery. The following stage-dependent success rates were obtained: stage I (13 patients) - 84.6%, stage II (22 patients) - 95.5%, stage III (14 patients) - 85.7%, stage IV (5 patients) - 80%. Under preventive aspects, teeth were extracted after a predefined scheme in 68 of all patients registered as being asymptomatic. No BRONJ was observed in 98.5%; the criterion also being absence of symptoms for a minimum period of 3 months after surgery. Surgical treatment is the treatment of choice in cases of BRONJ. Tooth extractions are rather unproblematic in asymptomatic patients if the predefined scheme is followed.