The diagnosis and management of malignant phaeochromocytoma and paraganglioma

Malignant phaeochromocytomas are rare tumours accounting for ~10% of all phaeochromocytomas; the prevalence of malignancy among paragangliomas is higher, especially those associated with succinate dehydrogenase subunit B gene mutations. Although a subset of these tumours has metastatic disease at initial presentation, a significant number develops metastases during follow-up after excision of an apparently benign tumour. Clinical, biochemical and histological features cannot reliably distinguish malignant from benign tumours. Although a number of recently introduced molecular markers have been explored, their clinical significance remains to be elucidated from further studies. Several imaging modalities have been utilised for the diagnosis and staging of these tumours. Functional imaging using radiolabelled metaiodobenzylguanidine (MIBG) and more recently, (18)F-fluorodopamine and (18)F-fluorodopa positron emission tomography offer substantial sensitivity and specificity to correctly detect metastatic phaeochromocytoma and paraganglioma and helps identify patients suitable for treatment with radiopharmaceuticals. The 5-year mortality rate of patients with malignant phaeochromocytomas and paragangliomas greater than 50% indicates that there is considerable room for the improvement of currently available therapies. The main therapeutic target is tumour reduction and control of symptoms of excessive catecholamine secretion. Currently, the best adjunctive therapy to surgery is treatment with radiopharmaceuticals using (131)I-MIBG; however, this is very rarely curative. Chemotherapy has been used for metastatic disease with only a partial and mainly palliative effect. The role of other forms of radionuclide treatment either alone or in combination with chemotherapy is currently evolving. Ongoing microarray studies may provide novel intracellular pathways of importance for proliferation/cell cycle control, and lead to the development of novel pharmacological agents.     

The optimal imaging of adrenal tumours: a comparison of different methods

Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1- and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [(131)I]-6-iodomethyl norcholesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [(123)I]- and [(131)I]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours.     

Dual-source computed tomography: advances of improved temporal resolution in coronary plaque imaging

OBJECTIVES: The aim of this study was to quantify image quality gains of a moving coronary plaque phantom using dual-source computed tomography (DSCT) providing 83 milliseconds temporal resolution in direct comparison to 64 slice single-source multidetector CT (MDCT) with a temporal resolution of 165 milliseconds. MATERIALS AND METHODS: Three cardiac vessel phantoms with fixed 50% stenosis and changing plaque configurations were mounted on a moving device simulating cardiac motion. Scans were performed at a simulated heart frequency of 60 to 120 bpm. Image quality assessment was performed in different anatomic orientations inside a thoracic phantom. RESULTS: A significant improvement of image quality using the DSCT could be found (P=0.0002). Relevant factors influencing image quality aside from frequency (P=0.0002) are plaque composition (P<0.0001), as well as orientation (P<0.0001). CONCLUSION: Scanning with 83 milliseconds temporal resolution improved image quality of coronary plaque at higher heart frequencies.     

Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility

BACKGROUND: The introduction of human leukocyte antigen (HLA)-matching in nonliving kidney transplantation has resulted into a better graft outcome, but also in an increase of waiting time, especially for patients with rare HLA phenotypes. We addressed the question of the differential influence of HLA-DR-matching versus HLA-A,B in clinical kidney transplantation. METHODS: We used Kaplan-Meier product limit method to estimate survival rates, and Cox proportional hazard regression for the estimation of relative risks (Hazard-ratios) for different variables. RESULTS: A single center study (n=456 transplants, performed between 1985 and 1999) showed that full HLA-DR compatibility leads to a lower incidence of biopsy confirmed acute rejections in the first 180 posttransplantation days. These results were substantiated using the Eurotransplant database (n=39,205 transplants performed between 1985 and 2005) where graft survival in the full HLA-DR compatible group was significantly better than in the incompatible. An additional positive effect of HLA-A,B matching was only found in the full HLA-DR compatible group. In both studies, the introduction of a single HLA-DR incompatibility eliminates the HLA-A,B matching effect. CONCLUSIONS: We propose to allocate postmortem kidneys only to patients with full HLA-DR compatibility, and use HLA-A,B compatibility as an additional selection criterion. All patients, irrespective of their ethnic origin, will profit since the polymorphism of HLA-DR is by far lower than that of HLA-A,B. Excessive kidney travel and cold ischemia time will be significantly reduced.     

Administration of antibiotics via the respiratory tract as monotherapy for pneumonia

There is increasing interest in applying alternatives to the systemic modes of administration of antimicrobial agents for the treatment of patients with pneumonia. We endeavored to accumulate and evaluate the published evidence on the role of aerosolized antimicrobials administered as monotherapy for patients with pneumonia through searches of PubMed, Scopus and relevant bibliographies. Seven relevant studies (one randomized controlled trial, four case series and two case reports), including 63 patients, were identified; 37% (23 out of 63) and 63% (40 out of 63) of these patients suffered from community-acquired and nosocomial (including ventilator-associated) pneumonia, respectively. Acinetobacter baumannii (41%), Gram-positive cocci (37%) and Pseudomonas aeruginosa (16%) were the pathogens most frequently isolated from sputum, tracheal aspirates, bronchoalveolar lavage and bronchial brush specimens. Colistin (49%), penicillin (37%) and aminoglycosides (17%) were the antimicrobials administered via the respiratory tract. Concurrent systemic antimicrobials (without activity against the isolated pathogens) were given to 33% (21 out of 63) of patients. Clinical cure and bacteriological eradication from the aforementioned specimens were observed in 86% (54 out of 63) and 85% (33 out of 39) of patients, respectively. For the 31 patients for whom data were available, all-cause mortality and attributable mortality were 36% (11 out of 31) and 10% (three out of 31), respectively. The very limited published data preclude any strong conclusions; however, the available data seem to suggest that aerosolized antimicrobial monotherapy for pneumonia should not be a priori excluded when systemic access is unavailable, denied by the patient or when concerns exist regarding bioavailability in the lungs or systemic toxicity. Clinicians are encouraged to publish any relevant experience in order for a considerable body of literature to be accumulated.     

Spontaneous renal bleeding in a dialysis patient with acquired cystic disease of the kidney: case report and review of the literature

The aim of this paper is to describe a rare clinical case of spontaneous haemorrhagic rupture of a multicystic kidney in a patient on haemodialysis for acquired cystic disease. We also discuss current issues about the management of this rare condition, with a short review of the literature.