Gerd Jürgen Ridder

Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs approximately US

Paragangliomas of the head and neck: diagnosis and treatment.

2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age <or=40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care.

Descending necrotizing mediastinitis: contemporary trends in etiology, diagnosis, management, and outcome.

Paragangliomas of the head and neck (HNP) represent rare tumors of neural crest origin. They are highly vascular neoplasms that are benign in the majority of cases. The site of origin defines the name given those tumors. In the head and neck, they most commonly occur at the carotid bifurcation, where they are referred to as carotid body tumors (CBT). Other common sites of origin are the jugular bulb (jugular paraganglioma; JP), the tympanic plexus on the promontory (tympanic paraganglioma; TP) and the vagal nerve (vagal paraganglioma; VP). Patients with cervical paragangliomas frequently present with a painless, slowly enlarging mass in the lateral neck. In many patients with TP and JP, tinnitus and hearing loss are early symptoms. JP patients often suffer from lower cranial nerve deficits. Evaluation by an imaging modality is necessary to establish the diagnosis. Imaging procedures frequently used include B-mode sonography with color-coded Doppler sonography, computed tomography (CT), magnetic resonance imaging (MRI) and digital substraction angiography (DSA). Debate exists in the literature regarding the different treatment modalities for paragangliomas which include surgery, radiotherapy and stereotactic radiosurgery. The role of preoperative angiography and embolization has also been a matter of discussion.The diagnostic work up and the different treatment options for patients with head and neck paragangliomas will be presented and discussed.

Malignant head and neck paragangliomas in SDHB mutation carriers.

Objective:To evaluate contemporary trends in etiology, diagnosis, management, and outcome of descending necrotizing mediastinitis (DNM) and to draw the clinicians attention on this probably underappreciated disease. Summary of Background Data:An uncommon but one of the most serious forms of mediastinitis is DNM which is caused by downward spread of deep neck infections and arises as a major complication of “banal” odontogenic, pharyngeal, or cervicofacial foci. As most studies are based on small patient populations, current data on risk factors, etiology, and outcome vary significantly. Also, the optimal form of treatment remains controversial. Methods:This retrospective study, which is the largest single-center study since 1960, is based on the management of 45 patients with DNM treated over a period of 12 years. Additionally, a meta-analysis of 26 studies on DNM published between 1999 and 2008 was performed and compared with own data and 2 previous meta-analyses covering the interval from 1960 to 1998. Results and Conclusions:Today DNM most commonly arises from pharyngeal foci and mixed polymicrobial aerobic and anaerobic infections. Reduced tissue oxygenation and impaired immune function promotes its development. Most cases of DNM are limited to the upper mediastinum and can be adequately drained by a transcervical approach. Formal thoracotomy should be reserved for cases extending below the plane of the tracheal bifurcation. Although DNM remains an aggressive infection with high morbidity, a favorable outcome can now be obtained in 85% of patients, even with this selective approach. Early diagnosis and surgical intervention are crucial.

Role of Cat-Scratch Disease in Lymphadenopathy in the Head and Neck

OBJECTIVE: Three of four paraganglioma syndromes (PGLs) have been characterized on a molecular genetic basis. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC gene mutations, and PGL 4 is caused by SDHB gene mutations. The objective of this study was to investigate whether PGLs are associated with malignant head and neck paragangliomas (HNPs). STUDY DESIGN AND SETTING: Through November 2005, we screened 195 HNP patients for mutations of the genes SDHB, SDHC, and SDHD. RESULTS: We detected 5 SDHC, 13 SDHB, and 45 SDHD gene mutations. In seven SDHB mutation carriers, there were distant metastases. No signs of metastases were found in SDHC and SDHD patients. One patient with a sporadic HNP presented with locally metastatic disease. CONCLUSIONS: SDHB mutations are associated with a high rate of malignant HNPs. SIGNIFICANCE: In SDHB patients, a three-body region imaging and scintigraphy or DOPA-PET must be performed to exclude metastases.

Spectrum and Management of Deep Neck Space Infections: An 8-Year Experience of 234 Cases

Bartonella henselae is the causative agent of cat-scratch disease (CSD), which usually manifests as acute regional lymphadenopathy. The causes of cervical lymphadenopathy, with special regard to CSD, were investigated in a study of 454 patients who presented with unclear masses in the head and neck from January 1997 through January 2001. Sixty-one patients (13.4%) experienced CSD; 54 (11.9%) had primary lymphadenopathy due to other infectious agents, and 41 (9.0%) had lymphadenopathy that occurred in association with primary infections of other organs. For 171 patients (37.7%), the cause of the cervical lymph node enlargement could not be found. B. henselae DNA was detected in extirpated lymph nodes only during the first 6 weeks of lymphadenopathy, which indicates that the results of polymerase chain reaction strongly depend on the duration of illness. CSD should be included in the differential diagnosis of adenopathy in the otorhinolaryngologic patient population, to avoid unnecessary treatment.

Navigation as a quality management tool in cochlear implant surgery.

OBJECTIVE: To study the clinical course and outcome of deep neck infections (DNI), with special emphasis on microbiology and histopathology. STUDY DESIGN: Two hundred thirty-four patients with DNIs were included in this study. Patients with peritonsillar or dental infections, infections arising from salivary glands, as well as subjects with abscesses caused by neck trauma were excluded. METHODS: Clinical analysis of all patients with DNIs who were treated between January 1, 1997 and May 31, 2005 in a single center. RESULTS: In 13 patients, the DNI was the first manifestation of a malignant tumor. In 17 cases, the DNI was associated with cat-scratch disease (CSD). Six patients suffered from tuberculosis, and in another 7, an infected lateral cleft cyst was found. In 176 patients, the origin of DNI remained unclear. CONCLUSIONS: Our results demonstrate that CSD, tuberculosis, and malignant tumors must be considered as possible causes of DNIs. The current study represents one of the largest series of DNIs in the modern medical literature.

Severe deep neck space infections and mediastinitis of odontogenic origin: clinical relevance and implications for diagnosis and treatment.

This cadaver study assessed the value of navigation in cochlear implant surgery. Cochlear implantation was simulated on a cadaver using a Stryker-Leibinger navigation system and a Nucleus 24 Contour implant. A conventional surgical strategy consisting of mastoidectomy, posterior tympanotomy, and cochleostomy was performed. The navigated surgical procedure was evaluated for accuracy, reliability, reproducibility, and practicability. The technology of computer-assisted surgery is applicable in cochlear implantation and beneficial in as much as the navigation-controlled implantation constitutes a non-invasive instrument of quality management. Nevertheless, in order to keep the point accuracy below one millimeter, a referencing method using concealed bordering anatomical structures may be further needed to perform the cochleostomy reliably under the guidance of a navigation system. More reproducible reference systems are needed if navigated lateral skull base surgery is to be fully relied upon.

Cat-scratch disease: Otolaryngologic manifestations and management

Conclusions. Early diagnosis and aggressive antimicrobial and surgical treatment are essential to successfully treat extensive cervico-mediastinal abscesses of odontogenic origin. Patient management should be performed by experienced clinicians well trained in managing possible complications. We recommend close clinical and radiological postoperative follow-up investigations with early surgical re-intervention if necessary. Objectives. While neck infections affecting the perimandibular space have a high prevalence and their clinical aspects have repeatedly been discussed, further spread of the inflammation and life-threatening situations have rarely been described. The objective was to determine clinical, diagnostic, and therapeutic aspects of severe neck infections of odontogenic origin. Emphasis was placed on grave descending deep neck space infections, sometimes resulting in mediastinitis as a life-threatening complication. Patients and methods. We reviewed 10 patients with severe odontogenic abscesses treated during an 8-year interval in a single center. Results: The submandibular space was the most frequently encountered location of deep neck space infections. Mediastinitis was found in five patients. The most frequent causative bacteria were Streptococcus and Bacteroides species. All patients underwent intravenous antibiotic treatment and surgical therapy. Mediastinotomy was inevitable in five cases and thoracotomy in one case. All patients survived.

ULTRASOUND-GUIDED CORE-NEEDLE BIOPSY IN THE DIAGNOSIS OF HEAD AND NECK MASSES: INDICATIONS, TECHNIQUE, AND RESULTS

OBJECTIVE: The bacteria Bartonella henselae has been known as the principal causative agent of cat-scratch disease (CSD) since 1992. It is an important cause of infectious lymphadenopathies in the head and neck. Nevertheless, CSD often remains unrecognized in cases of cervicofacial lymph node enlargement. STUDY DESIGN: Between January 1997 and May 2003, we conducted a prospective clinical study including 721 patients with primarily unclear masses in the head and neck. RESULTS: CSD was diagnosed by serology and molecular investigations in 99 patients (13.7%; median age 33 years). Cervicofacial lymphadenopathy was the most common manifestation. Atypical manifestation of CSD including Parinauds oculoglandular syndrome, swelling of the parotid gland and erythema nodosum were diagnosed in 8.1%, 8.1%, and 2.0% of cases, respectively. CONCLUSIONS: Our results demonstrate that CSD is a major cause of enlarged cervicofacial lymph nodes and should therefore be included in the differential diagnosis of lymphadenopathy in the head and neck region.