Siegmar Reinert

Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients

Background: Due to low energy levels in microphotodiode-based subretinal visual prostheses, an external power supply is mandatory. We report on the surgical feasibility and the functional outcome of the extraocular part of an approach to connect a subretinal prosthesis to an extracorporeal connector in the retro-auricular space via a trans-scleral, transchoroidal cable. Methods: Seven volunteers with retinitis pigmentosa received an active subretinal implant; energy was supplied by gold wires on a trans-sclerally, transchoroidally implanted polyimide foil leading to the lateral orbital rim where it was fixated and connected to a silicone cable. The cable was implanted subperiostally beneath the temporal muscle using a trocar to the retro-auricular space where it penetrated the skin for connection to a stimulator. To avoid subretinal movement of the implant, three tension relief points have been introduced. Results: All implantations were performed as planned without complications, and no serious adverse events occurred in the postoperative period. Fixation of the implants was stable throughout the entire study duration of 4 weeks; permanent skin penetration proved to be uncomplicated. Motility was minimally restricted in downgaze and ab-/adduction. Explantation was uneventful. Conclusion: The above-described procedure provides a method for stable fixation of a subretinal device with a trans-scleral, transchoroidal cable connection to an extracorporeal connector.

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.

Computer-assisted surgical treatment of orbitozygomatic fractures.

Orbitozygomatic fractures pertain to the most common injuries in craniofacial trauma patients. Accurate fracture reduction is of high importance for a successful outcome. This pilot study was performed to assess the potential benefit of surgical navigation to aid in orbitozygomatic fracture reduction. A non-comparative series of five consecutive patients with severely displaced orbitozygomatic fractures was treated using the guidance of computed tomography (CT)-based surgical navigation. Using a previously developed software platform, the fracture was reduced virtually by a three-dimensional shifting of the orbitozygomatic complex within the patients preoperative multimodal CT data set. This treatment plan was transferred to a navigation system. Fracture reduction was performed according to the treatment plan using surgical navigation. Intraoperative control of fracture reduction by comparing the real with the virtual bone position using surgical navigation showed up as a helpful tool. Accurate treatment planning and immediate evaluation of craniofacial surgery outcome are the benefits of the new approach demonstrated. A major drawback of the presented approach is a high consumption of human and financial resources. A larger clinical series with long-term follow-up will be needed to determine reproducibility and cost-effectiveness. In addition to bone repositioning, a future application may include simulation of craniofacial osteotomies.

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.

Mucormycosis: necrotizing soft tissue lesion of the face.

Spontaneous necrotizing soft tissue lesions of the face are seen rarely in a maxillofacial surgeon’s daily practice. Depending on the type of tissue involved, they can be differentiated into necrotizing cellulitis, fasciitis, and myonecrosis. Necrotizing cellulitis affects the skin and is usually caused by monomicrobial infection. Group A Streptococcus, Staphylococcus, aerobic coliforms, and Clostridia are known to be the main causal agents. Necrotizing fasciitis affects primarily the subcutaneous tissues, with little initial effect on the skin but necrosis in advanced stages of the disease. It occurs as the result of polymicrobial synergistic aerobic and anerobic gas-producing infection with streptococci and, less often, the mucormycosiscausing agents Rhizopus, Mucor, or Absidia. Myonecrosis primarily affects the muscle and is caused by Clostridium perfringens, Streptococcus pyogenes, or group B Streptococcus. Clinical differentiation between these types can cause problems because they can appear to be very similar. Although necrotizing soft tissue lesions are seen in healthy individuals, they most commonly occur in patients who are immunocompromised by degenerative diseases, abnormal metabolic states, malignant diseases, major burns, immunosuppressive drugs, acquired immune deficiency syndrome, or prolonged antibiotic therapy.1 Necrotizing soft tissue infections are characterized by a high mortality rate, because many of these lesions are rapidly progressive infections that cause extensive necrosis of the subcutaneous tissues followed by gangrene of the skin and systemic toxicity.1 We present the case of a rarely seen spontaneous necrotic soft tissue lesion of the face caused by the mucormycosis-causing agent Absidia corymbifera in a patient who had undergone bone graft transplantation after she was diagnosed with acute myeloid leukemia.

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.

A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells

BackgroundBiomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide molecule endonuclease DNaseX (DNaseI-like 1) has been used to identify the Apo10 protein epitope that marks tumor cells with abnormal apoptosis and proliferation. The transketolase-like protein 1 (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/Warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies.MethodsExpression of Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo10 and TKTL1 have been used prospectively for epitope detection in monocytes (EDIM)-blood test in patients with OSCC (n = 50), breast cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74).ResultsPositive Apo10 and TKTL1 expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+ subgroup showed the worst disease-free survival rate in OSCC.EDIM-Apo10 and EDIM-TKTL1 blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity of 97.3% for the detection of carcinomas independent of the tumor entity.ConclusionsThe combined detection of two independent fundamental biophysical processes by the two biomarkers Apo10 and TKTL1 allows a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. Further prospective trials are warranted to validate this new concept for the diagnosis of neoplasia and tumor recurrence.

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.

Image-guided sphenoid wing meningioma resection and simultaneous computer-assisted cranio-orbital reconstruction: technical case report.

OBJECTIVE Resection of large intraosseous sphenoid wing meningiomas is traditionally associated with significant morbidity. Rapid prototyping techniques have become widely used for treatment planning. Yet, the transfer of a treatment plan into the intraoperative situs strongly depends on the experience of the individual surgeon. CLINICAL PRESENTATION Extensive resection with orbital decompression was planned and performed on the basis of rapid prototyping and surgical navigation techniques in a 44-year-old woman presenting with a large sphenoid wing meningioma on the right infiltrating the orbit. RESULTS Tumor resection was simulated on a stereolithography model of the patients head. The stereolithography model was scanned using computed tomography (CT) and the defect geometry was used to create a custom-made titanium implant. The implant consisted of a solid titanium core and a spot-welded titanium mesh surrounding the core, allowing for minor intraoperative adjustments of the implant size by reducing the mesh size. The stereolithography model with the incorporated implant was CT scanned again and the CT data were fused with the patients original CT data. The implant borders indicating the resection borders were marked within the patients CT data set. This treatment plan was transferred to an optical navigation system. Intraoperatively, tumor resection was performed using surgical navigation. CONCLUSION In the presented case report, the combination of computer-assisted planning using rapid prototyping techniques and image-guided surgery allowed for an extensive tumor resection precisely according to a preoperative treatment plan in a patient presenting with a large intraosseous sphenoid wing meningioma. A larger clinical series with a long-term follow-up period will be needed to determine the reproducibility.