Christian Offergeld

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I–III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Clinical Features of Paraganglioma Syndromes

Head and neck paragangliomas (HNPs) and pheochromocytomas are rare tumors. Sporadic and hereditary forms are recognized. Four different paraganglioma syndromes (PGLs 1-4) have been described: PGL 1 is associated with mutations of the succinate dehydrogenase (SDH) subunit D (SDHD) gene; PGL 3 is caused by SDHC gene mutations; PGL 4 is caused by SDHB gene mutations; the susceptibility gene for PGL 2 is unknown. The objective of this study is to review distinct clinical features of the different PGLs. An international registry for HNPs was founded in Freiburg, Germany, in 2000. The data presented in this article have been acquired from registered HNP patients who have been screened for mutations of the genes SDHB, SDHC, and SDHD. Approximately 30% of apparent sporadic HNPs are caused by a germline mutation in one of these genes. Patients with PGL 1 or 4 have a very high lifetime risk of developing HNPs as well as thoracic and abdominal pheochromocytomas. Compared with sporadic HNPs, tumors developing in SDHB, SDHC, and SDHD mutation carriers arise at a significantly younger age. The SDHB mutations are associated with a high percentage of malignant paraganglionic tumors. We recommend molecular genetic screening of all HNP patients for SDHB, SDHC, and SDHD gene mutations. Mutation carriers must be screened for paraganglial tumors in the head, neck, thorax, and abdomen. Appropriately timed surgical intervention will minimize disease-specific morbidity and mortality. Lifelong follow-up is mandatory.

Experimental Investigation of Rotational Tomography in Reconstructed Middle Ears with Clinical Implications

A large air-bone-gap after ossiculoplasty may be due to a malpositioned or displaced prosthesis. Rotational tomography (RT) has the potential to provide high-resolution images of implants without artifacts and with less radiation dosage than CT scan. Twenty-seven temporal bone specimens underwent measurements of middle ear transfer function using Laser-Doppler-Vibrometry (LDV) before and after placement of ossicular replacement prostheses (PORPs, TORPs) made of titanium. RT was performed on all specimens. RT allowed 3-dimensional viewing of the temporal bone, accurate localization of implants within the reconstructed middle ear and determination of angles between the inserted prostheses and the tympanic membrane (TM) and/or the malleus handle (MH). Presence or absence of contact between the implant and the TM, malleus or stapes could be clearly visualized. Displaced prostheses were readily identified. The functional LDV-measurements for TORPs showed a trend favoring coupling to the malleus handle, while for PORPs, coupling to the TM was favored. For PORPs, sound transmission was worse with increasing angles between the PORP and stapes superstructure (p<0.05). Following our experimental results RT is an innovative, relevant and useful imaging technique to obtain immediate postoperative feedback after ossicular reconstruction and to precisely determine the position of middle ear implants.

Characterization of endolymphatic sac tumors and von Hippel–Lindau disease in the International Endolymphatic Sac Tumor Registry

Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel–Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking.

Flat panel CT following stapes prosthesis insertion: an experimental and clinical study

ObjectivesAnatomical information of the middle and inner ear is becoming increasingly important in post-operative evaluation especially after stapesplasty with unsuccessful improvement of the air-bone gap (ABG). So far computed tomography (CT) has been the first choice for detection of reasons for recurrent hearing loss. CT has the disadvantage of metal-induced artefacts after insertion of middle ear implants and of a relatively high irradiation dose.MethodsFlat panel CT (fpCT) was performed in three temporal bone specimen after experimental insertion of different stapes prostheses, aiming to validate the accuracy of fpCT of the middle and inner ear. Additionally, 28 consecutive patients, supplied with different stapes prostheses underwent post-operative fpCT to compare the pre- and post-operative hearing results with the determined prosthesis position in the middle and inner ear.ResultsIn all cases, fpCT showed a statistically significant correlation between hearing improvement and prosthesis position. This technique provided detailed post-operative information of the implant position in patients and temporal bone specimen.ConclusionsThe new imaging technique of fpCT allows the immediate and almost artefact-free evaluation of surgical results following stapesplasty. Further benefits are a lower irradiation dose and higher isovolumetric resolution compared with standard CT.Key Points• Flat panel computed tomography (fpCT) helps otosurgeons design precise stapes protheses• fpCT allows a prediction of the postoperative hearing outcome in patients• fpCT is an adequate imaging technique for immediate postoperative quality control. Postoperative management of patients with prosthesis-related complications is more appropriate

Clinical investigation of flat panel CT following middle ear reconstruction: a study of 107 patients

ObjectivesAfter middle ear reconstruction using partial or total ossicular replacement prostheses (PORP/TORP), an air–bone gap (ABG) may persist because of prosthesis displacement or malposition. So far, CT of the temporal bone has played the main role in the diagnosis of reasons for postoperative insufficient ABG improvement. Recent experimental and clinical studies have evaluated flat panel CT (fpCT) as an alternative imaging technique that provides images with high isovolumetric resolution, fewer metal-induced artefacts and lower irradiation doses.MethodsOne hundred and seven consecutive patients with chronic otitis media with or without cholesteatoma underwent reconstruction by PORP (n = 52) or TORP (n = 55). All subjects underwent preoperative and postoperative audiometric testing and postoperative fpCT.ResultsStatistical evaluation of all 107 patients as well as the sole sub-assembly groups (PORP or TORP) showed a highly significant correlation between hearing improvement and fpCT-determined prosthesis position. FpCT enables detailed postoperative information on patients with middle ear reconstruction.ConclusionsFpCT is a new imaging technique that provides immediate feedback on surgical results after reconstructive middle ear surgery. Specific parameters evaluated by fpCT may serve as a predictive tool for estimated postoperative hearing improvement. Therefore this imaging technique is suitable for postoperative quality control in reconstructive middle ear surgery.Key Points• Flat panel CT offers advantages with regard to artefacts and radiation dose.• FpCT provides higher isovolumetric resolution of temporal bone and middle ear implants.• FpCT allows prediction of the postoperative hearing outcome in patients.• FpCT is an important tool for immediate postoperative quality control.• FpCT improves postoperative management of patients with complications following ossicular replacement

Modern trends in the management of head and neck paragangliomas.

Head and neck paragangliomas (HNPG) are rare, mostly benign neoplasms that usually exhibit an indolent growth pattern although they can be associated with compression and infiltration of adjacent cranial nerves and, depending on the site of origin, also bone and intracranial structures. Less than 5 % of the tumors are considered malignant based on the presence of metastases and not local invasion. Carotid body tumors accounts for two-thirds of HNPG, whereas vagal paragangliomas are showing the highest tendency toward malignant character. Despite the usual treatment of benign tumors is surgery, the risks of the treatment-related complications and potential deterioration of quality of patient’s live, however, should not be greater than the risk brought by the tumor in its natural course. Watchful waiting and radiotherapy are widely accepted in the management of vestibular schwannomas, a tumor that is usually indolent but, like HNPG, also has an unpredictable growth pattern. Review of different national tumor registry databases revealed that in the United States there has been a significant shift in management of vestibular schwannomas over a decade, with increasing tendency toward observation and radiotherapy, whereas the proportion of operated cases declined to near a half of the total [1–3]. Similar studies on the trends of treatment are lacking in HNPG. Systematic analysis of the literature has shown that most of the HNPG have been treated surgically, with no data on the impact of observation in the management of these tumors [4, 5].

Quality management in middle ear surgery: controversies regarding preoperative imaging.

Today a large variety of different imaging techniques are available for middle ear investigation. However, imaging is not suitable to give essential information in every case on the surgical strategy to be chosen. This article discusses the most frequent indications for preoperative imaging and the relevant techniques. CT scanning, MRI and rotational tomography are taken into consideration as well as traditional X-ray investigations like e.g. ‘Schüller’s view’. In general, preoperative imaging should only be performed in a patient if certain specific questions can be answered. The experience of the investigator to interpret the images may influence the choice of imaging as well as the equipment he has access to.

Evaluation des Dresdner Tympanoplastik Modells (DTM)

The training of microsurgical motor skills is essentiell for surgical education if the interests of the patient are to be safeguarded. In otosurgery the complex anatomy of the temporal bone and variations necessitate a special training before performing surgery on a patient. We therefore developed and evaluated a simplified middle ear model for acquiring first microsurgical skills in tympanoplasty.The simplified tympanoplasty model consists of the outer ear canal and a tympanic cavity. A stapes model is placed in projection of the upper posterior tympanic membrane quadrant at the medial wall of the simulated tympanic cavity. To imitate the annular ligament flexibility the stapes is fixed on a soft plastic pad. 41 subjects evaluated the model´s anatomical analogy, the comparability to the real surgical situation and the general model properties the using a special questionnaire.The tympanoplasty model was very well evaluated by all participants. It is a reasonably priced model and a useful tool in microsurgical skills training. Thereby, it closes the gap between theoretical training and real operation conditions.

Experimental Simulation of Clinical Borderline Situations in Temporal Bone Specimens After Ossiculoplasty

Objectives: One reason for insufficient hearing improvement with a distinct air–bone gap after ossiculoplasty with implantation of partial or total ossicular replacement prostheses can be the dislocation or minimal shifting of the prosthesis. The aim of this study was the simulation of common clinical borderline situations with minimal shifting of the prosthesis in temporal bone specimens after ossiculoplasty. It was furthermore the goal to identify these specific situations through imaging by cone beam computed tomography (cbCT) and direct visual inspection using the operation microscope. Additionally, the functional status was evaluated using laser-Doppler vibrometry (LDV). Design: We used a total of four temporal bone specimens for this study. A reconstruction with a partial ossicular replacement prostheses was performed in three specimens and with a total ossicular replacement prostheses in one specimen, with good initial acoustic properties. Subsequently, one specific type of prosthesis failure was simulated in each specimen, respectively, by minimally shifting, tilting, or bending the prostheses from their initial positions. These changes were introduced step-by-step until a borderline situation just short of complete acoustic decoupling was reached. Each step was examined using both LDV and cbCT and observed through the operation microscope. Results: LDV was able to quantify the mechanic function of the ossicular chain after most of the manipulation steps by demonstrating the effect of any shifting of the prosthesis on the middle ear transfer function. However, in some situations, the middle ear transfer function was better with a visually more advanced failure of the prosthesis. In addition, cbCT showed most of the steps with excellent resolution and was able to delineate changes in soft tissue (e.g., cartilage covering). Conclusion: cbCT seems to be a promising imaging technique for middle ear problems. As cbCT and LDV exhibited slightly different advantages and disadvantages regarding the demonstration of borderline situations, the combination of both techniques allowed for a more precise evaluation of middle ear reconstructions. Knowledge of the specific characteristics of these methods and their possible combination might help otologists and otosurgeons to refine indications for revision surgery and improve their personal patient counseling.