Skull base osteomyelitis: incidence of resistance, morbidity, and treatment strategy.

OBJECTIVES/HYPOTHESIS: The pathogeny of osteomyelitis of the skull base has evolved over time with the emergence of ciprofloxacin-resistant Pseudomonas strains and significant fungal infections, both of which seem to bring a higher morbidity. The aims of this study were 1) to document the incidence of ciprofloxacin-resistant Pseudomonas aeruginosa over the past 7 years; 2) to assess morbidity by a radiologic score, the occurrence of cranial nerve palsies, and the duration of the hospital stay, according to the pathogenesis; and 3) to propose a treatment strategy. STUDY DESIGN: Retrospective chart review of necrotizing external otitis cases from 2004 to 2011. The setting was the Department of ENT Surgery, Lariboisière Hospital, Paris. METHODS: Thirty-one patients were included. Radiological scores were assessed based on the initial computed tomography scans or magnetic resonance imaging, which specified the anatomical territory involved. Nerve palsies, the duration of hospitalization, and the radiological scores were analyzed with regard to the pathogen. RESULTS: Twenty-eight patients had a bacterial disease. Of the 20 strains of P. aeruginosa identified, five (25%) were ciprofloxacin-resistant P. aeruginosa. Three patients (10%) had a fungal infection due to Aspergillus flavus. Nerve palsies, radiological scores, and hospitalization durations were significantly higher for patients with resistant strains and A. flavus. CONCLUSIONS: In our series, the prevalence of ciprofloxacin-resistant Pseudomonas strains increased over time. Along with fungal infections, they formed a group with a higher morbidity than that of ciprofloxacin-sensitive Pseudomonas infections that furthermore did not respond to oral outpatient treatment. This is why pathogen identification using biopsies is sometimes required to start a prolonged treatment.

Endolymphatic sac tumors in von Hippel-Lindau disease: report of three cases.

OBJECTIVES: To illustrate the diagnostic and pathophysiologic issues of endolymphatic sac tumors (ELSTs) and its clinical association with von Hippel-Lindau (VHL) disease and to demonstrate the interest of genetic testing in such cases. STUDY DESIGN: Retrospective analysis of 3 cases of ELST with VHL in 3 different clinical and prognostic situations. MAIN OUTCOMES: The first case was diagnosed on the concomitant finding of a central nervous system lesion. The familial genetic testing revealed the presence of the VHL mutation in an asymptomatic daughter, which justified regular follow-up. In the second case of known VHL syndromic disease, the pathophysiologic role of the endolymphatic sac was questioned, with vertigo as the initial, unique symptom of ELST. In the third case, a giant hypervascularized ELST, initially diagnosed as jugular paraganglioma, was the unique manifestation of VHL disease. The young age of the patient could explain the absence of other tumors. CONCLUSION: Diagnosis of ELSTs may be difficult especially when the original site of the lesion cannot be clearly identified. Such tumors may be revealed or may develop with VHL disease. On presentation of a lytic, vascularized tumor of the posterior face of the petrous bone, clinicians should systematically search for other manifestations of VHL disease and propose a VHL genetic testing for patients, and relatives in case of a positive test, to detect early asymptomatic other tumors. The type of VHL mutation might predict the aggressiveness.

Evolving concepts in the management of jugular paraganglioma: a comparison of radiotherapy and surgery in 88 cases.

Surgery for jugular paraganglioma (PGL) tumors often results in the acquisition of neurological deficits where none had been present previously. This has a significant impact on the quality of life. Radiotherapy is a recognized alternative therapy. The aim of this study was to compare the results of radiotherapy and surgery for the management of jugular PGL in terms of function and tumor control to define a treatment algorithm. We conducted a retrospective and comparative analysis of the treatment of 41 patients by conventional radiotherapy and 47 patients by surgery via tertiary referral at an academic medical center. Forty-seven patients with type C and/or D jugular PGLs (mean age, 46 years) underwent surgery after endovascular embolization between 1984 and 1998 using an infratemporal fossa type A approach. The facial nerve was transposed in 18 patients. An adjunctive neurosurgical procedure was required in 14 patients. Mean follow-up was 66 months (range, 17 months to 14 years). Forty-one patients with type C jugular PGLs (mean age, 59.5 years) were treated by external beam or conformational radiotherapy between 1988 and 2003 with a total mean dose of 45 Gy (range, 44 to 50 Gy). Mean follow-up was 50 months (range, 18 months to 13 years). The primary outcome measures were tumor control and cranial nerve status. Surgical resection, total or subtotal, yielded an overall 86% rate of either cure or tumor stabilization. Radiotherapy achieved local control in 96% of patients. For surgery, the main postoperative complications were dysphagia, aspiration, and facial paralysis. Patients treated by radiotherapy developed minor disabilities. We concluded that radiotherapy and surgery achieve similar oncologic outcomes, but the former achieves tumor control with less morbidity. Our data favor radiotherapy as treatment for jugular PGLs, but we acknowledge that the aims of these two treatment modalities are different, namely, eradication of tumor by surgery versus stabilization of tumor with radiotherapy. The search for the better quality of life has to be weighed against the uncertainty of the long-term behavior of the tumor.

An animal model of central auditory pathway imaging in the rat brain by high resolution small animal positron emission tomography.

CONCLUSIONS: Our study demonstrated that high resolution animal positron emission tomography (PET) can non-invasively assess the change in glucose metabolism of the central auditory pathway including the inferior colliculus and auditory cortex in the rat. OBJECTIVES: The traditional in vitro approach with immunohistochemical staining or autoradiography to assess chronological changes or topographic arrangement of central auditory pathway required sacrificing a large number of animals. Inter-individual difference is also a major concern. Therefore, development of an in vivo animal model using PET imaging would be a rational method to overcome these shortcomings. MATERIALS AND METHODS: Small animal PET scan using (18)F-fluorodeoxyglucose (FDG) as a functional marker was performed in rats. Each animal was serially scanned before and after unilateral cochlear ablation, with and without acoustic stimulation. The images were analyzed by the region of interest (ROI) method. Ratios of radioactivity at the inferior colliculus and auditory cortex and a referenced cerebral cortex between bilateral hemispheres were measured. RESULTS: These scans demonstrated several brain structures including the inferior colliculus (IC) and cortex (B). Moreover, unilateral cochlear ablation decreased the radioactivity at contralateral IC and auditory cortex (C) areas. Differences may reach 33% in IC and 27% in C, and average radioactivity ratios were 1.24+/-0.08 and 1.18+/-0.07 in selected adjacent sections, respectively.

Clinical impact of somatostatin receptor scintigraphy in the management of tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia (TIO) is a rare condition due to phosphate wasting secondary to the release of a phosphatonin, fibroblast growth factor-23. Attempts to identify the tumor by physical examination and/or conventional imaging are sometimes unrewarding. In such cases, somatostatin receptor scintigraphy with octreotide has been successfully proposed. METHODS: Two case reports and a review of the literature allow to demonstrate the diagnostic usefulness of octreotide and the therapeutic value of somatostatin. RESULTS: Octreotide studies were positive in 79% of 24 reported TIO, including our 2 cases. In one of our patients with incomplete removal of the tumor, octreotide therapy was unable to improve hypophosphatemia, despite a decrease in fibroblast growth factor-23 levels by 30%. Similar results were achieved in most of the reported cases. Surgical procedures were effective in these cases and resulted in complete clinical and biochemical recovery. CONCLUSION: We highlight the impact of somatostatin receptor evaluation in the management of TIO.

Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events.

BACKGROUND: We aimed to evaluate the additional information of 18 fluorodeoxyglucose (FDG) arterial uptake with respect to other conventional cardiovascular risk factors and arterial calcifications in patients with stable cancer. METHODS AND RESULTS: We compared the rate of cardiovascular events in 2 groups of patients with (n = 45) and without (n = 56) enhanced arterial 18FDG uptake, matched for the main clinical parameters. The extent and intensity of 18FDG uptake were quantified. A calcification index was also determined. About one third of the selected patients had a history of cardiovascular events and thus could be defined as "vulnerable patients." Old cardiovascular events (>6 months before or after positron emission tomography [PET]) and recent cardiovascular events (<6 months before or after PET) were significantly more frequent in the high-FDG uptake group than in the low-FDG uptake group (48% vs 15%, respectively [P = .0006], and 30% vs 1.8%, respectively [P = .0002]). The extent of 18FDG arterial uptake was the unique factor significantly related to the occurrence of a recent event by either logistic regression or discriminant analysis (P = .004 for all). Conversely, calcium index was the single factor related to old events (P = .004 and P = .002, respectively). CONCLUSIONS: Extensive arterial 18FDG uptake might be an indicator of an evolving atherosclerotic process and should be mentioned in PET/computed tomography reports.

Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.

OBJECTIVE: Hereditary paraganglioma (PGL) syndromes result from germline mutations in genes encoding subunits B, C and D of the mitochondrial enzyme succinate dehydrogenase (SDHB, SDHC and SDHD). SDHB-related PGLs are known in particular for their high malignant potential. Recently, however, malignant PGLs were also reported among a small minority of Dutch carriers of the SDHD founder mutation D92Y. The aim of the study was to investigate which SDHD mutations are associated with malignant PGL. DESIGN: Case histories; collaborative study between referral centres in France, the USA, and the Netherlands. PATIENTS: Six unrelated patients with metastatic PGLs of either sympathetic or parasympathetic origin. MEASUREMENTS: Assessment of SDHD mutations underlying malignant PGL. RESULTS: Germline SDHD mutations underlying metastatic PGL were G148D, Y114X, L85X, W43X, D92Y, and IVS2+5G-->A. CONCLUSION: Our findings indicate that malignant SDHD-related PGL is associated with several mutations besides D92Y.

Role for positron emission tomography in skeletal diseases.

Imaging plays a prominent role in the diagnosis and management of rheumatic diseases. Conventional imaging methods provide high-resolution structural information but usually fail to distinguish between active lesions and residual changes. Positron emission tomography (PET) with the tracer 18F-fluorodeoxyglucose (18F-FDG) was recently introduced into clinical practice as a means of obtaining information on both structure and metabolic activity. 18F-FDG-PET is widely used in oncology and may be valuable in patients with infections or inflammatory diseases, most notably vasculitis. Although encouraging results have been published, the number of studies remains small, as 18F-FDG-PET is an expensive investigation that is not available everywhere. Further work is needed to determine the cost-effectiveness ratio of 18F-FDG-PET in patients with infections or inflammatory diseases. Imaging plays a prominent role in the diagnosis and management of many musculoskeletal diseases. Although considerable progress has been made recently, the structural information supplied by conventional imaging methods is inadequate in some patients. Positron emission tomography (PET) after injection of 18fluorodeoxyglucose (18F-FDG) provides information on tissue metabolism. The usefulness of 18F-FDG-PET in oncology is now widely recognized. Other uses are emerging, in part thanks to the development of new cameras that combine dedicated detectors and an X-scanner in order to ensure accurate three-dimensional localization of metabolically active lesions. However, the exact role for 18F-FDG-PET needs to be studied in larger populations of patients.

Bone metastases from head and neck paragangliomas: uncommon MR findings in an uncommon condition--report of three cases.

Malignancy (defined as metastatic disease) has been reported in nearly 5% of head and neck paragangliomas. Metastases preferentially target the lymph nodes, lung, liver, or bone. We describe three patients with multiple silent bone metastases exhibiting a fatty halo at MRI that coexisted with expansive bone lesions. In all cases, (123)I-metaiodobenzylguanidine ((123)MIBG) scintigraphy showed no abnormal tracer uptake, whereas (111)In-pentetreotide scintigraphy visualized a few silent bone metastases. These findings indicate that MRI should be included in the staging of paraganglioma patients with risk factors for malignancy.

Systemic sarcoidosis: the "leopard-man" sign.

Systemic sarcoidosis is often diagnosed late. A 37 year-old man from the Antilles was admitted for evaluation of arthralgia, subcutaneous and cutaneous nodules, multiple enlarged lymph nodes, and an epididymal lump. He had been given a diagnosis of epididymal and nodal tuberculosis but had not responded to antitubercular agents. Gallium-67 scintigraphy showed multiple hot spots in the soft tissues, skin, muscles, mediastinum, and lachrymal glands, producing a diffuse dappled pattern. Magnetic resonance imaging of the thighs confirmed the muscular and subcutaneous involvement. Systemic sarcoidosis was diagnosed. Prednisone therapy was promptly effective. We suggest the term "dappled-body sign" or "leopard-man sign" to designate the heretofore undescribed scintigraphic pattern in our patient.

Are somatostatin analogs therapeutic alternatives in the management of head and neck paragangliomas?

BACKGROUND: Although mostly benign, head and neck paragangliomas require active management because of injury to adjacent neurovascular structures. Surgery, usually preceded by embolization, allows for complete tumor removal. However, surgery carries a significant risk of iatrogenic injury, related to tumor volume. Because paragangliomas express somatostatin receptors with high density, we investigated the effect of a long-acting somatostatin analogue (OCT-LAR) on the size of such tumors to reduce iatrogenic injury and related the percentage of tumor shrinkage to a tracer uptake index calculated on somatostatin receptor scintigraphy (SRS). METHODS: In eight of the first nine patients, 30 mg of OCT-LAR was given intramuscularly every 28 days for 3 doses; one patient withdrew after the first dose because of side effects. Conventional imaging with computed tomography (CT) scan or magnetic resonance imaging plus SRS revealed 18 paraganglioma sites. For each lesion, a tracer uptake index was calculated on pretreatment SRS. All 18 tumors were measured by CT scan before treatment and 1 month after the third injection. RESULTS: The average percent tumor shrinkage was 4.0 +/- 10.0%, and the average tumor reduction was 1.0 +/- 3.8 cm (P = .27, NS). Only 2 of the 18 paragangliomas shrank by more than 20%; these two tumors belonged to the only one secreting patient. There was no significant relation between tracer uptake index and tumor response. CONCLUSION: These results suggest 1) that SRS results do not predict OCT-LAR efficacy on paraganglioma size, and 2) OCT-LAR is not useful in the preoperative management of paragangliomas.

Somatostatin and somatostatin analog scintigraphy: any benefits for rheumatology patients?

Somatostatin is a hormone that regulates several physiological cell processes via specific receptors expressed throughout the body, in particular by nerve cells, many neuroendocrine cells, and cells mediating inflammation and immune responses. Somatostatin receptor scintigraphy achieved by administration of somatostatin labeled with a gamma-emitting isotope has become an integral part of the work-up and treatment-monitoring program in patients with neuroendocrine tumors, most of which overexpress somatostatin receptors. Several studies have convincingly established that somatostatin receptor scintigraphy benefits patients with a number of chronic inflammatory diseases, including sarcoidosis and other granulomatous diseases. In the evaluation of hematological diseases and detection of mesenchymatous tumors manifesting as oncogenic osteomalacia, the preliminary results are sufficiently promising to warrant larger studies aimed at defining the role for this noninvasive whole-body imaging technique. In the treatment area, the development of somatostatin analogs with antisecretory and antiproliferative effects has radically changed the management of gastroenteropancreatic neuroendocrine and pituitary tumors. The antiinflammatory and analgesic effects of these drugs remain incompletely understood, but may prove useful in a number of autoimmune diseases.

Clinical impact of somatostatin receptor scintigraphy in the management of paragangliomas of the head and neck.

UNLABELLED: Paragangliomas are neuroendocrine tumors expressing somatostatinergic receptors and, thus, may be imaged by somatostatin receptor scintigraphy (SRS). The purpose of the study was to assess the contribution of SRS in the management of paraganglioma of the head and neck. METHODS: (111)In-Pentetreotide (148 MBq) was intravenously administered to 3 groups of patients. Group A consisted of 9 patients with tumors of the head and neck that did not exhibit typical radiologic features of paragangliomas and required further diagnostic evaluation. Group B consisted of 28 patients with known paragangliomas or paraganglioma metastatic lymph node who required staging and assessment of multicentricity. Group C consisted of 5 asymptomatic relatives of affected individuals who required screening. All patients underwent clinical, laboratory, radiologic, and audiovestibular evaluation. RESULTS: In group A (n = 9), SRS was positive in 6 cases, 4 paragangliomas and 2 meningiomas, and negative in 3 patients in whom the initial diagnosis of paraganglioma was excluded. In group B (n = 28), SRS was strongly positive in all of the 34 head and neck masses diagnosed on conventional imaging to be paragangliomas; it localized 1 primary malignant paraganglioma and revealed 9 unexpected foci. In group C (n = 5), SRS was positive in 3 of the 5 relatives, CT or MR scan confirming the diagnosis of paraganglioma in all cases. CONCLUSION: Because of very high sensitivity in detecting paraganglioma, SRS should be included in a multiple-step strategy for patients' management. It could be useful in ruling out the diagnosis of schwannoma, but its major advantage may involve patients' staging. Once biologic genetic testing of affected patients' relatives evidenced the predisposing mutation, SRS could be proposed to identify individuals who express the disease.

The [14C-N-methyl]-erythromycin breath test dosimetry complies with the French regulations for radiation safety.

The [14C-N-methyl]-erythromycin breath test (14C-ERMBT) is one of the most valuable probes for liver cytochrome P450-3A4 activity in humans. In order to extend the use of this test in France, we herein provide safety data regarding either patient dosimetry or worker exposure to [14C-N-methyl]-erythromycin. In order to determine the maximum radiation exposure for patient and nuclear medicine technician following one intravenous 14C-ERMBT [111 kiloBequerel (kBq)], we have used the dosimetric data gathered in animal studies and extrapolated to humans using a weight-based method, approximate data provided by the French Society of Radioprotection and erythromycin pharmacokinetics in humans, considering always the worst conditions for the patient and worker exposure determination. The radioactivity administered to a patient after one 14C-ERMBT was equal to 108.8 kBq (i.e. 98% of the total radioactivity in the 14C-erythromycin vial) leading to a patient effective dose of 20 microsievert (microSv) and a maximum effective dose after 14CO2 inhalation by the exposed worker of 16 microSv compared with a mean individual annual effective dose from natural and artificial radioactivity exposure of 3500 microSv in France. The 14C-ERMBT is safe and complies with the European regulations regarding the administration of 14C-labelled compounds in humans. It can therefore be used in clinical research in France without any particular safety requirement.