Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas

Objective: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). Patients: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. Results: Gender (P=0.0086), UICC stage (P=0.0140) and R‐class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19‐9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I–II):UICC (III–IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19‐9 (<100 U/ml):CA 19‐9 (≥100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3–4, 5 and 6 points (P=0.000001) and clinical groups with 3–4 and 5–6 points (P=0.0103) achieved statistically significant difference. Conclusions: We propose a clinical and prognostic scoring system predictive of long‐term survival after surgical resections for ICC.     

Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study

Background  

Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections.     

Prevalence,clinical correlates and treatment of permanent atrial fibrillation among the elderly: insights from the first prospective population-based study in rural Greece

To investigate the prevalence of permanent atrial fibrillation (AF), its clinical associated conditions and treatment status in the elderly population in rural Greece. 720 people (46.1% males) older than 65 years (mean age: 72.5 ± 5.7 years) living in four villages in rural Greece were screened with an electrocardiogram (response rate: 90.5%) for the presence of permanent AF. They underwent a physical examination, including blood pressure (BP) measurement, and body mass index (BMI) calculation, in addition to an interview about their medical history, physical activity, smoking habits, alcohol consumption and medication use. Subjects with AF for whom anticoagulants were contraindicated were identified and stroke risk stratification was performed using the CHADS2 algorithm. The prevalence of permanent AF was 5% (6.6% among men and 3.6% among women) and it increased with age. In the entire population, ECG evidence of myocardial ischaemia and ventricular premature beats were independently associated with the presence of permanent AF (OR 5.266; 95% CI 2.22–12.49, P = 0.0001 and OR 2.61; 95% CI 1.059–6.432, P = 0.037, respectively), while female sex was independently associated with the absence of the AF (OR 0.327; CI 0.147–0.729, P = 0.006). From those patients who were eligible for anticoagulation, 40.6% were treated with anticoagulants, 34.3% were given antiplatelets therapy and the rest received no antithrombotic treatment. This is the first prospective study demonstrating the prevalence, clinical correlates and treatment status of permanent AF in Greece. These results confirm the high prevalence of permanent AF among the elderly and underscore the issue regarding anticoagulants underutilization.     

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.     

A highly divergent microsatellite facilitating fast and accurate DRB haplotyping in humans and rhesus macaques

The DRB region of the MHC in primate species is known to display abundant region configuration polymorphism with regard to the number and content of genes present per haplotype. Furthermore, depending on the species studied, the different DRB genes themselves may display varying degrees of allelic polymorphism. Because of this combination of diversity (differential gene number) and polymorphism (allelic variation), molecular typing methods for the primate DRB region are cumbersome. All intact DRB genes present in humans and rhesus macaques appear to possess, however, a complex and highly divergent microsatellite. Microsatellite analysis of a sizeable panel of outbred rhesus macaques, covering most of the known Mamu-DRB haplotypes, resulted in the definition of unique genotyping patterns that appear to be specific for a given haplotype. Subsequent examination of a representative panel of human cells illustrated that this approach also facilitates high-resolution HLA-DRB typing in an easy, quick, and reproducible fashion. The genetic composition of this complex microsatellite is shown to be in concordance with the phylogenetic relationships of various HLA-DRB and Mamu-DRB exon 2 gene/lineage sequences. Moreover, its length variability segregates with allelic variation of the respective gene. This simple protocol may find application in a variety of research avenues such as transplantation biology, disease association studies, molecular ecology, paternity testing, and forensic medicine.