18F-FDG PET/CT in the post-operative monitoring of patients with adrenocortical carcinoma.

CONTEXT: The role of (18)F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the post-operative monitoring of patients with adrenocortical carcinoma (ACC) is still unclear. OBJECTIVE: To assess the accuracy of FDG PET/CT to diagnose ACC recurrence in a real world setting. DESIGN AND METHODS: Retrospective evaluation of data of 57 patients with presumed ACC recurrence at CT scan who underwent FDG PET/CT within a median time of 20 days. We compared the results of either FDG PET/CT or CT with a gold standard confirmation of recurrence (positive histopathology report of removed/biopsied lesions or radiological progression of target lesions at follow-up) to assess their diagnostic performance at different body sites to correctly categorize target lesions. We also assessed whether FDG PET/CT findings may be useful to inform the management strategy. RESULTS: In 48 patients with confirmed ACC recurrence, we found that FDG PET/CT had lower sensitivity than CT in diagnosing liver and lung recurrences of ACC. FDG PET/CT had higher specificity than CT in categorizing liver lesions. FDG PET/CT had a greater positive likelihood ratio than CT to identify liver and abdominal ACC recurrences. The management strategy was changed based on FDG PET/CT findings in 12 patients (21.1%). CONCLUSIONS: The greater sensitivity of CT may be partly expected due the specific inclusion criteria of the study; however, the greater specificity of FDG PET/CT was particularly useful in ruling out suspected ACC recurrences found by CT. Thus, use of FDG PET/CT as a second-line test in the post-operative surveillance of ACC patients following CT finding of a potential recurrence may have a significant impact on patient management.

A miRNA Signature in Human Cord Blood Stem and Progenitor Cells as Potential Biomarker of Specific Acute Myeloid Leukemia Subtypes.

MicroRNAs (miRNAs) are important regulators of several cellular processes. During hematopoiesis, specific expression signatures have been reported in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation. Here we explored the expression of miRNAs in umbilical cord blood stem (HSC) and progenitor cells (HPC) and compared it to unilineage granulocyte and granulo-monocyte differentiation as well as to primary blasts from patients with acute myeloid leukemia (AML). CD34 + CD38- ad CD34 + CD38 + cells were profiled using a global array consisting of about 2000 miRNAs. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative biologically enriched functions and networks. At least 15 miRNAs to be differentially expressed between HSC and HPC cell population, a cluster of 7 miRNAs are located in the q32 region of human chromosome 14 (miR-377-3p, -136-5p, 376a-3p, 495-3p, 654-3p, 376c-3p and 381-3p) whose expression decreased during the early stages of normal myelopoiesis but were markedly increased in a small set of AML. Interestingly, miR-4739 and -4516, two novel microRNA whose function and targets are presently unknown, showed specific and peculiar expression profile during the hematopoietic stem cells differentiation into unilineages and resulted strongly upregulated in almost all AML subsets. miR-181, -126-5p, -29b-3p and -22-3p resulted dis-regulated in specific leukemias phenotypes. This study provides the first evidence of a miRNA signature in human cord blood stem and progenitor cells with a potential role in hematopoietic stemness properties and possibly in leukemogenesis of specific AML subtypes.

Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors.

MicroRNAs (miRNAs) regulate cell proliferation, differentiation and death during development and postnatal life. The expression level of mature miRNAs results from complex molecular mechanisms, including the transcriptional regulation of their genes. MiR-223 is a hematopoietic-specific miRNA participating in regulatory signaling networks involving lineage-specific transcription factors (TFs). However, the transcriptional mechanisms governing its expression levels and its functional role in lineage fate decision of human hematopoietic progenitors (HPCs) have not yet been clarified. We found that in CD34(+)HPCs undergoing unilineage differentiation/maturation, miR-223 is upregulated more than 10-fold during granulopoiesis, 3-fold during monocytopoiesis and maintained at low levels during erythropoiesis. Chromatin immunoprecipitation and promoter luciferase assays showed that the lineage-specific expression level of mature miR-223 is controlled by the coordinated binding of TFs to their DNA-responsive elements located in 'distal' and 'proximal' regulatory regions of the miR-223 gene, differentially regulating the transcription of two primary transcripts (pri-miRs). All this drives myeloid progenitor maturation into specific lineages. Accordingly, modulation of miR-223 activity in CD34(+)HPCs and myeloid cell lines significantly affects their differentiation/maturation into erythroid, granulocytic and monocytic/macrophagic lineages. MiR-223 overexpression increases granulopoiesis and impairs erythroid and monocytic/macrophagic differentiation. Its knockdown, meanwhile, impairs granulopoiesis and facilitates erythropoiesis and monocytic/macrophagic differentiation. Overall, our data reveal that transcriptional pathways acting on the differential regulation of two pri-miR transcripts results in the fine-tuning of a single mature miRNA expression level, which dictates the lineage fate decision of hematopoietic myeloid progenitors.

A candidate anti-HIV reservoir compound, auranofin, exerts a selective 'anti-memory' effect by exploiting the baseline oxidative status of lymphocytes.

Central memory (T(CM)) and transitional memory (T(TM)) CD4(+) T cells are known to be the major cellular reservoirs for HIV, as these cells can harbor a transcriptionally silent form of viral DNA that is not targeted by either the immune system or current antiretroviral drug regimens. In the present study, we explored the molecular bases of the anti-HIV reservoir effects of auranofin (AF), a pro-oxidant gold-based drug and a candidate compound for a cure of AIDS. We here show that T(CM) and T(TM) lymphocytes have lower baseline antioxidant defenses as compared with their naive counterpart. These differences are mirrored by the effects exerted by AF on T-lymphocytes: AF was able to exert a pro-differentiating and pro-apoptotic effect, which was more pronounced in the memory subsets. AF induced an early activation of the p38 mitogen-activated protein kinase (p38 MAPK) followed by mitochondrial depolarization and a final burst in intracellular peroxides. The pro-differentiating effect was characterized by a downregulation of the CD27 marker expression. Interestingly, AF-induced apoptosis was inhibited by pyruvate, a well-known peroxide scavenger, but pyruvate did not inhibit the pro-differentiating effect of AF, indicating that the pro-apoptotic and pro-differentiating effects involve different pathways. In conclusion, our results demonstrate that AF selectively targets the T(CM)/T(TM) lymphocyte subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell death pathways.

PET in the clinical work-up of patients with spondylodiscitis: a new tool for the clinician?

AIM: The role of 18F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) in the clinical management of patients with inflammatory diseases (e.g., chronic inflammatory diseases, fever of unknown origin, ostemyelitis, prosthesis infections) is still under investigation. The aim of the present study was to evaluate the usefulness of PET in the diagnostic work-up of patients with spondylodiscitis and to compare it with magnetic resonance imaging (MRI). METHODS: This retrospective study included 33 patients with suspected/confirmed spondylodiscitis. Two groups were created: 1) disease definition (n=24); and 2) treatment assessment (N.=16, 21 exams). Disease status was defined on the basis of data collected for symptoms, hematological parameters, imaging studies and histological findings, when available. Qualitative and semiquantitative analysis of the PET images was performed. The minimum duration of follow-up was 6 months. RESULTS: For the Disease Definition group, FDG-PET showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 92.9%, 50%, 72.2%, 83.3%, and 75%, respectively, and MRI showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 50%, 76.9%, 100%, and 81.3%, respectively. For the Treatment Assessment group, FDG-PET showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 90%, 81.8%, 81.8%, 90%, and 85.7%, respectively, and MRI showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 16.7%, 58.3%, 100% and 61.5%, respectively. No significant differences were observed between qualitative and semiquantitative evaluation of PET scans. CONCLUSION: PET and MRI showed similar accuracy in the diagnosis of spondylodiscitis, indicating that PET can be used when MRI is doubtful or unavailable. PET was more accurate and more specific than MRI in treatment assessment, suggesting that PET should be preferred over MRI for determining when treatment can be safely discontinued.

Role of integrated PET/CT with [¹8F]-FDG in the management of patients with fever of unknown origin: a single-centre experience.

PURPOSE: Fever of unknown origin (FUO) is a diagnostic challenge for the wide range of possible causes involved. The aim of our work was to evaluate the role of [(18)F]-fluorodeoxyglucose positron emission tomography computed tomography ([¹8F]-FDG-PET/CT) in managing patients with classical FUO. MATERIALS AND METHODS: Twenty-four consecutive patients (16 women, eight men; mean age, 56.5 years) with a diagnosis of FUO based on routine investigations were retrospectively studied. All underwent [¹8F]-FDG-PET/CT, which was considered true positive when the result was in agreement with the final diagnosis. RESULTS: A final diagnosis was reached in 17 of 24 patients (vasculitis, n=5; autoimmune disorder, n=2; neoplasm, n=3; infectious disease, n=6; biliary microlithiasis, n=1). In the remaining seven cases, no final diagnosis was established. PET-CT was useful in identifying aetiology in 11 patients, showing a diagnostic yield of 46% (11/24). Among the 11 cases with a negative PET scan, 10 did not show a worsening of the clinical condition. CONCLUSIONS: This study underlines the crucial role of [¹8F]-FDG-PET/CT in managing patients with FUO. If prospective trials on this topic confirm the present findings, PET/CT should be incorporated in the routine diagnostic work-up of patients with classical FUO.

Prognostic role of the PET parameter maximum standardized uptake value in non small cell lung cancer: analysis in tumour of diameter ≥ and <25 mm.

AIM: The aim of this study was to evaluate whether the primary tumour maximum standardized uptake value (SUV(max)) plays an independent prognostic role in patients with non small cell lung cancer (NSCLC) and whether this role is limited by partial volume effect (PVE) and motion artefacts. METHODS: One hundred and fifty-three consecutive patients underwent PET exam, surgery (R0 resection) and follow-up (mean 20.3; range 6-44.8 months). Correlation with Disease Free and Overall Survival (DFS, OS) was evaluated in the entire population for: SUV(max), clinical and histopathological features and pathological stage. To evaluate the PVE and motion artefacts' interferences on SUV calculation, the correlation between SUV(max) and DFS/OS was also calculated in the groups of patients with tumour diameter ≥ and < than 25 mm (group A and B, respectively). RESULTS: In the entire population only TNM and SUV(max) resulted correlated with DFS/OS. However, SUV(max) was significantly correlated with DFS/OS in group A but not in group B. Furthermore, only in the group of patients with primary tumour diameter ≥ 25 mm (group A), tumour diameter, tumour histotype, and tumour necrosis resulted significantly related with SUV(max) at both uni and multivariate analysis. CONCLUSION: TNM together with SUV(max) could be useful in giving a better prognostic stratification of patients with NSCLC; however technical limitations in the SUV calculation must be taken into account in patients with tumour diameter <25 mm.

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias.

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies.

Bone marrow disease detection with FDG-PET/CT and bone marrow biopsy during the staging of malignant lymphoma: results from a large multicentre study.

AIM: To compare the accuracy of bone marrow biopsy (BMb) and positron emission tomography (PET) in bone marrow disease (BMD) detection, in a large multicentre population of patients with new diagnosis of malignant lymphoma. METHODS: PET and BMb were performed to complete disease staging in 337 consecutive patients: 130 Hodgkin's disease (HD), 207 aggressive non Hodgkin's lymphoma (NHL). Sensitivity, specificity and accuracy of both techniques in BMD detection were evaluated and compared. RESULTS: 87 patients with BMD (25 positives at both exams, 27 only at the BMb and 35 only at the PET study). PET vs. BMb were reordered: sensitivity: 69% vs. 59.8%; specificity: 99.2% vs. 100%; accuracy: 91.4% vs. 89.6%; positive predictive value: 96.8% vs. 100%; negative predictive value: 90.2% vs. 87.7%. CONCLUSION: The sensitivity of PET and BMb is similar (69% and 60%, respectively), PET and BMb are complementary: in fact out of 87 patients with confirmed BMD only 25 are positive at both exams, while 27 only at the BMb and 35 only at the PET exam; the integration of PET findings with BMb ones increases the diagnostic accuracy. Consequentially PET is essential during the staging of malignant lymphomas.

Comparison between turnaround time and cost of herpes simplex virus testing by cell culture and polymerase chain reaction from genital swabs.

Clinical diagnosis of genital herpes simplex virus (HSV) (GH) infection is insensitive and non-specific and requires laboratory confirmation. In this study we compared viral culture and the amplification of HSV DNA by polymerase chain reaction (PCR) with respect to turnaround time and cost. We compared 182 swabs submitted to our laboratory between March and May 2005, which were tested using MRC-5 cell culture, with 168 genital swabs submitted during the same months in 2006, and were tested by PCR. We concluded that PCR testing in our laboratory has significantly improved the turnaround time, with 68.4% of tests having been reported in less than 24 hours. This in turn significantly improved the service provided for the diagnosis of genital herpes without additional costs.

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes.

MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In this study, we analysed, using a quantitative real-time PCR approach, the expression of 12 granulocytic differentiation signature miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in APL blasts as compared with normal promyelocytes differentiated in vitro from CD34+ progenitors. Patients successfully treated with all-trans-retinoic acid (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR-15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL-associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor alpha (RARalpha), might be involved in the transcriptional repression of miR-107, -342 and let-7c. We found that PML/RARalpha binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/RARalpha paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34alpha. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.

PLZF-mediated control on c-kit expression in CD34(+) cells and early erythropoiesis.

The promyelocytic leukemia zinc-finger protein (PLZF) is a transcription factor and c-kit is a receptor tyrosine kinase associated with human disease, particularly in hematopoietic cells. MicroRNAs (miRs) are post-transcriptional regulators of gene expression, and c-kit has been described as a target of miRs-221 and -222 in erythropoiesis. In the present study, we identified c-kit as a target of PLZF in normal and leukemic cells. Particularly, in erythropoietic (E) culture of CD34(+) progenitors, PLZF is downregulated, whereas c-kit expression at both the mRNA and protein levels inversely increases during the first days of E differentiation. In functional experiments, PLZF transfection induces c-kit downregulation, inhibits E proliferation and delays differentiation, whereas PLZF knockdown induces opposite effects, independently of miRs-221 and -222 expression. The inverse correlation between PLZF and c-kit expression was found in normal CD34(+)38(+/-) hematopoietic progenitor/stem cells and in acute myeloid leukemias of M0/M1 French-American-British subtypes, suggesting that the control of PLZF on c-kit expression may be crucial at the level of the stem cell/progenitor compartment. Altogether, our data indicate a new mechanism of regulation of c-kit expression that involves a transcriptional control by PLZF in CD34(+) cells and early erythropoiesis.

Feasibility of the sentinel node biopsy in anal cancer.

AIM: Anal cancer is a rare neoplasm. According to a European Organization for Research and Treatment of Cancer multivariate analysis, synchronous inguinal lymph node metastasis occurs in 10-25% of patients and constitutes an independent prognostic factor for local failure and overall mortality. METHODS: Inguinal lymph node status was assessed using the sentinel node technique in 35 patients with anal cancer. RESULTS: Histology revealed 23 squamous carcinomas, 10 basaloid carcinomas, 1 squamous carcinoma with basaloid areas and 1 spinocellular epithelioma associated with areas of Bowen's disease. Disease stage was T1 in 5 patients, T2 in 18, T3 in 11 and T4 in 1 patient. Lympho-scintigraphy using a GE Millennium gamma camera was performed after peritumoral injection of 37 MBq of 99mTc colloid. Surgical sentinel node biopsy with a portable Scintiprobe MR 100 (Politech, Carsoli, Italy) had a detection rate of 97.1%. Inguinal metastases were detected in 7 (20%) patients, in 2 of which metastasis was bilateral. CONCLUSIONS: Given the correlation between prognosis and node involvement, sentinel node biopsy can be considered a simple method for adequate pretreatment staging of anal carcinoma. Use of the technique could avert the need for prophylactic inguinal radiotherapy in N0-N1 patients, thus reducing the morbidity associated with inguinal radiotherapy. Consistent follow-up is required to evaluate long-term results:

Dual-phase FDG-PET: delayed acquisition improves hepatic detectability of pathological uptake.

PURPOSE: The aim of this study was to evaluate whether the acquisition of delayed images could improve the detectability of liver pathological uptakes. MATERIALS AND METHODS: Ninety-five consecutive patients with suspected liver metastases underwent a dual-phase positron emission tomography (PET) scan. All patients underwent a whole-body PET/computed tomography (CT) scan (PET-1) acquired 1 h post [18F]fluorodeoxyglucose (FDG) injection, and a liver PET/CT scan [that is, one or two fields of view (FOV) of the upper abdomen; PET-2] acquired 2 h postinjection. In all cases, image reconstruction was performed as 3D reconstruction algorithm Fourier rebinning (FORE) iterative, FOV 50 cm, image matrix size 128 x 128. Both studies were evaluated qualitatively and semiquantitatively [background standard uptake values (SUV)mean of the liver, lesion SUVmax and SUVmean and ratio SUVmean lesion/background). RESULTS: Thirty-seven of 95 patients (38.9%) presented liver lesions at both PET-1 and PET-2 exams, whereas there were two (2.2%) only at PET-2. Eighty-one liver lesions were identified at both PET studies, whereas there were nine (11.1%) only at PET-2. Furthermore, at PET-2, we had a statistically significant reduction of SUVmean background values (p < 0.001, Wilcoxon test) and a concomitant increase of SUVmean lesion values (p < 0.001, Wilcoxon test), ratio lesion to background (p < 0.001, Wilcoxon test). CONCLUSIONS: Acquisition of delayed images improved the hepatic detection of pathological FDG uptake.

Role of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and conventional techniques in the staging of patients with Hodgkin and aggressive non Hodgkin lymphoma.

PURPOSE: The aim of this study was to evaluate the role of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the staging of Hodgkin's and aggressive non-Hodgkin's lymphoma (HL and NHL), comparing it with conventional diagnostic methods, i.e. contrast-enhanced CT and bone marrow biopsy. MATERIALS AND METHODS: Sixty-five consecutive patients (30 HL and 35 NHL) who underwent conventional disease staging and FDG-PET/CT were included. Concordance between conventional methods and PET was established when both procedures identified the same disease stage. Discordant findings were investigated further by using other diagnostic techniques (ultrasonography or magnetic resonance imaging) and/or clinical follow-up. RESULTS: PET correctly staged 93.8% of enrolled patients (61/65), whereas conventional techniques correctly staged 89.2% (58/65; p=NS, Chi(2) test). There was complete concordance in 54/65 patients (83.1%); among the remaining 11 cases, PET upstaged eight patients (seven true positive and one false positive), and downstaged three (all false negative). In 5/65 patients, chemotherapy treatment was modified on the basis of PET findings. CONCLUSIONS: Our data confirm the high accuracy of FDG-PET/CT in staging HL and NHL. FDG-PET/CT should therefore be used routinely in the initial evaluation of both patient subgroups.

Role of whole-body 18F-choline PET/CT in disease detection in patients with biochemical relapse after radical treatment for prostate cancer.

PURPOSE: The aim of this study was to evaluate the role of whole body 18F-choline (FCH) positron emission tomography-computed tomography (PET-CT) in detecting and localising disease recurrence in patients presenting biochemical relapse after radical treatment for prostate cancer. MATERIALS AND METHODS: Fifty-six consecutive patients with increased serum prostate-specific antigen (PSA) levels after radical prostatectomy were included in the study. None of them was receiving hormone treatment at the time of the examination or had been treated during the previous 6 months. All patients underwent whole-body 18F-choline PET imaging, and the pathological findings were compared with those of further imaging exams, biopsy and follow-up. On the basis of the PSA levels, we divided our patient population into three subgroups: PSA < or = 1, 1 < PSA < or = 5, and PSA > 5 ng/ml. RESULTS: Overall, the PET scan detected disease relapse in 42.9% of cases (24/56). PET sensitivity was closely related to serum PSA levels, showing values of 20%, 44% and 81.8% in the PSA < or = 1, 1 < PSA < or = 5 and PSA > 5 ng/ml subgroups, respectively. CONCLUSIONS: In patients with biochemical relapse after radical treatment for prostate cancer, 18F-choline PET-CT represents a single step, whole-body, noninvasive study that allows disease detection and localisation. The disease detection rate is related to serum PSA levels.

FDG-PET in the detection of bone marrow disease in Hodgkin's disease and aggressive non-Hodgkin's lymphoma and its impact on clinical management.

AIM: Identification of bone marrow disease (BMD) is a crucial step in the diagnostic work-up of patients with lymphoma. In lymphoma staging, bone marrow biopsy (BMb) is considered as the gold standard, despite its limitations. The aim of this study was to compare the usefulness of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) vs BMb in the detection of BMD in patients with Hodgkin's disease (HL) or aggressive non-Hodgkin's lymphoma (NHL) and its impact on therapy. METHODS: A total of 194 consecutive patients with malignant lymphoma were referred for staging. The clinical stage was defined according to the Ann Arbor classification by means of contrast enhanced computed tomography (CT), BMb and whole body FDG-PET/CT scan. Sensitivity, specificity, accuracy in BMD evaluation were calculated for PET and BMb. RESULTS: FDG-PET vs BMb: sensitivity 65.3% vs 55.1%; specificity 98.6% vs 100%; accuracy 90.2% vs 88.7%; positive and negative predictive value 94.1% and 89.3% vs 100% and 86.8%, respectively. Although PET and BMb had similar sensitivity and accuracy, BMD was identified by both methods in only 10 out of 49 patients. There were no significant differences in PET and BMb accuracy between the HL and the NHL patients. Moreover, treatment regimen was changed in 12 patients on the basis of FDG-PET findings. CONCLUSION: Our study demonstrates that BMb and FDG-PET are complementary in the evaluation of BMD. FDG-PET improves the sensitivity of BMb, especially in the presence of focal BMD. Performing FDG-PET before BMb is advised for optimal biopsy site targeting.

Hepatitis E: a complex and global disease.

Thirty years after its discovery, the hepatitis E virus (HEV) continues to represent a major public health problem in developing countries. In developed countries, it has emerged as a significant cause of non-travel-associated acute hepatitis. HEV infects a wide range of mammalian species and a key reservoir worldwide appears to be swine. Genomic sequence similarity between some human HEV genotypes and swine HEV strains has been identified and we know that humans can acquire HEV infection from animals. Although for the most part the clinical course of HEV infection is asymptomatic or mild, significant risk of serious disease exists in pregnant women and those with chronic liver disease. In addition, there are data on the threat of chronic infections in immunocompromised patients. Beyond management of exposure by public health measures, recent data support that active immunisation can prevent hepatitis E, highlighting the need for vaccination programmes. Here we review the current knowledge on HEV, its epidemiology, and the management and prevention of human disease.