Air Crescent Sign Research Articles

Pathogen identification by nuclear imaging – almost there?

Invasive fungal disease (IFD) in immunocompromised patients is a major infective cause of morbidity and mortality, with rates of death up to 90 % [1]. A key factor is the challenge of early diagnosis of IFD. In patients with haematological malignancy following intensive chemotherapy, immunosuppression and/or allogeneic haematopoietic stem cell transplantation, it is rarely possible to obtain the diagnostic material to definitively establish the presence of an IFD. The reasons for this are multiple, and include profound pancytopenia and poor performance status, which make tissue sampling of the lung (the main site for invasive aspergillosis, IA) hazardous. Equally, laboratory biological tests for IA have shown limited efficacy in the setting of blood sampling [2, 3], whereas bronchoalveolar lavage fluid appears to be a better material to assay, but bronchoscopy is an invasive intervention and may not be possible in an ill patient. All these factors, combined with post-mortem data showing higher rates of IFD than diagnosed ante-mortem [4], have led to empirical therapy as the standard of care in many centres around the world. The definition of empirical IFD therapy used throughout the literature is the commencement of treatment based on the clinical scenario alone, with the commonest situation being persistent neutropenic fever despite the use of broad-spectrum antibiotics. However, building on recent clinical studies [5–7], current management algorithms for IFD emphasize the importance of attempting to make a diagnosis, rather than relying on an empirical approach alone [8, 9]. CT scanning of the chest has a central role in the management of IA, with characteristic findings (nodules with or without a halo, consolidation with cavitation or an air crescent sign) supporting the diagnosis of IFD [10]. However, as the gold standard of a histological diagnosis or culture from sterile material is rarely possible, it becomes immediately obvious that even in a diagnosis-driven strategy combining imaging and galactomannan detection (the only widely used biomarker for IA), treatment is usually given without definitive proof of IA! Furthermore, while imaging of the chest with CT can support the diagnosis of IA, there are numerous alternative infections, as well as other disease processes; and galactomannan detection itself is associated with falsenegatives, false-positives and issues of reproducibility. The paper by Petrik et al. [11] offers hope of moving the field forward by combining imaging with pathogen detection. They have exploited the dependence on iron of many microorganisms, including Aspergillus fumigatus. In ironlimiting environments, A. fumigatus produces large amounts of siderophores, which are iron-chelating peptides that scavenge Fe and facilitate its uptake back into the organism [12]. Siderophores are essential for A. fumigatus virulence and deletions of genes involved in siderophore biosynthesis significantly impair fungal virulence [13]. Petrik et al. have taken advantage of the similarity of iron and gallium chemistry, already widely exploited in the use of Ga citrate, to label two siderophores with the short-lived, generatorproduced isotope Ga. They found that both compounds had good in vitro characteristics with respect to stability and specific uptake into A. fumigatus in culture as demonstrated by competition by either excess iron or unlabelled siderophore. Using small-animal PET/CT imaging in an immunocompromised rat model of lung infection with A. fumigatus, S. G. Agrawal Division of Haemato-Oncology, St Bartholomews Hospital and Blizard Institute, Queen Mary University of London, London EC1A 7BE, UK

Editorial Commentary: Galactomannan Antigen Testing for Diagnosis of Invasive Aspergillosis in Pediatric Hematology Patients

Invasive fungal diseases, in particular those due to Aspergillus spp., are increasing in incidence and constitute an important cause for morbidity and mortality in children and adolescents with hematologic malignancies and those undergoing allogeneic hematopoietic stem cell transplantation (HSCT) [1]. A contemporary retrospective analysis demonstrated that corticosteroid therapy, neutropenia, immunosuppressive therapy, malignancy, and allogeneic HSCT are the most common risk factors for invasive aspergillosis in pediatric age groups [2]. The overall case fatality rate of invasive aspergillosis in this study was 53%, which is similar to that seen in adult patients. Invasive aspergillosis significantly contributes to the in-house mortality of children with acute lymphoblastic and myeloid leukemia, lymphoma, allogeneic HSCT, and solid organ transplantation. In a retrospective cohort study using a national database of hospital inpatient stays during 2000, 18% (122 of 666) of children with invasive aspergillosis died in the hospital, compared with 1% (1736 of 151 537) of similarly immunocompromised children without invasive aspergillosis [3]. Despite substantial achievements over the past 2 decades, diagnosis and treatment of invasive fungal diseases in children and adolescents are still limited by a number of factors. As a matter of fact, not all antifungal agents are approved in the pediatric population, the appropriate dosage of several drugs has not been established for all age groups, and postmarketing data providing information on safety and efficacy of approved agents under real-life circumstances are scant. Similarly, the value of newer diagnostic tools is not defined in the pediatric population, although they are of major impact for establishing preventive and treatment strategies of invasive aspergillosis [4]. Whereas both the halo sign and the air-crescent sign revealed by pulmonary computed tomography scan are common and highly suggestive for invasive mold infection in adult patients and are included as clinical criteria in the revised definitions of invasive fungal disease set forth by the European Organization for Research and Treatment of Cancer and the Mycosis Study Group (EORTC/MSG) [5], radiographic findings in immunocompromised children with proven pulmonary invasive fungal disease are often nonspecific. In younger children (aged <5 years) in particular, typical signs of pulmonary invasive fungal disease are not seen in the majority of patients. In contrast, multiple nodules or fluffy masses and infiltrates that look like mass lesions are frequently reported [2]. Testing galactomannan (GM), a polysaccharide cell-wall component that is released by all Aspergillus spp. during cell growth, has been evaluated in multiple studies in adults and is included as a microbiological criterion in the revised definitions of invasive fungal disease by the EORTC/MSG consensus group and in a number of Editorial Commentary

Fluid rim sign: a new sonographic sign of soft tissue aspergillosis

The air crescent sign is a well-known important diagnostic finding in invasive pulmonary aspergillosis. Herein we report a distinctive but rare ultrasonographic appearance in a patient with myositis secondary to Aspergillus flavus infection, which can be considered as the soft tissue counterpart of the air crescent sign.

Pulmonary fungal infections after bone marrow transplantation: the value of high-resolution computed tomography in predicting their etiology

Background The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high-resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT. Methods Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis (n=52), candidiasis (n=19) and cryptococcosis (n=14) groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality. Results Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k &gt;0.75). There was a significant difference in occurrence ratio of mass among the three groups (P=0.02). Occurrence ratio of mass (43.3%, 13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%, 2/10; 14.3%, 1/7). There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation. Conclusions The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.

Invasive pulmonary aspergillosis in neutropenic patients: Early diagnosis by thoracic high-resolution CT scan.

e19713 Background: The aim of this study was to determine the utility of thoracic high resolution CT scan (HRCT) in the characterization of lung infiltrates for the early diagnosis of invasive pulmonary aspergillosis (IPA) in febrile neutropenic patients. Methods: We included hematology patients (acute leukemia/aplastic anemia) with febrile neutropenia in this study. We took chest x-rays at admission and at onset of fever or development of respiratory signs/symptoms. We did HRCT scan of the chest when fever had lasted for more than 4 days of antibiotic therapy or if the patient had signs/symptoms suggestive of pulmonary involvement or when chest X- ray showed abnormalities. Patterns of parenchymal infiltrates and the presence of nodular lesions, halo sign, cavitation, air crescent sign and fungal ball were noted. IPA was classified as proven, probable or suspected as per EORTC case definitions [excluding radiological criteria]. Calculation of sensitivity and specificity of HRCT in diagnosing IPA was based on these groups. Results: We studied 76 febrile episodes. Chest x-ray abnormalities were seen in 49 (61%) patients.HRCT scan of the chest showed abnormalities in 63 (84%) patients. Normal chest x-ray with abnormal CT was seen in 19(24%) patients. Typical CT findings included nodules in 24 (43%), nodules with halo sign in 19 (34%), segmental consolidation in 34 (61%), cavitation/air crescent sign in 9 (16%), fungal ball in 4(7%), pleural effusion in 11(20%) and hilar/paratracheal lymphadenopathy in 7 (13%). Multiple abnormalities were seen in 36 (47) % of cases. There were 32 cases of suspected IPA and 1 probable IPA. The overall sensitivity and specificity of HRCT for diagnosing IPA was 96% and 65% respectively. The sensitivity and specificity of the halo sign was 39% and 81% and that of the air crescent sign was 27% and 94%. Some of the larger nodules and consolidations in patients with suspected IPA showed a central hypodensity on non-contrast CT (‘hypodense sign’). These radiological findings were useful in the early institution of anti-fungal therapy in these patients. Conclusions: High resolution CT scan is superior to conventional chest x-ray for the early diagnosis of IPA in neutropenic patients.

Sixteen cases of pulmonary sclerosing haemangioma: CT findings are not definitive for preoperative diagnosis

To describe and assess computed tomography (CT) imaging findings of pathologically confirmed pulmonary sclerosing haemangioma (PSH), a rare benign tumour, in 16 patients. This study was approved by the human investigation committees of the two participating institutions, and the requirement of informed consent was waived. Findings from CT examinations in 16 patients with pathologically confirmed PSH were retrospectively reviewed. Two radiologists in consensus assessed the location, size, contour, and border of nodules, as well as the enhancement patterns. The study comprised 16 patients (two male and 14 female) aged 30-70 years. PSHs appeared as well-defined, round or ovoid masses with a diameter of 2.2±0.3cm, and were generally demonstrated as juxtapleural masses (94%) on CT. Calcification (13%), the air crescent sign (13%), and a prominent pulmonary artery (25%) in the tumours were also demonstrated in the cohort. The mean tumour attenuation value at CT was 30±3HU before intravenous administration of contrast media, and was significantly lower than that of the enhanced phase (79±3HU, p<0.05). Twelve tumours (75%) enhanced homogeneously compared with four tumours (25%) which enhanced heterogeneously. The diameters of the heterogeneously enhanced tumours were larger than those of the homogeneously enhanced tumours (p<0.05). The relatively characteristic CT findings include a markedly contrast-enhanced juxtapleural mass with homogeneous enhancement for the smaller tumours (<3cm in diameter) or heterogeneous enhancement for the larger tumours (>3cm). However, CT findings are not definitive for preoperative diagnosis of PSH.

Pulmonary Aspergilloma Mimicking Metastasis from Papillary Thyroid Cancer

Whole-body scans (WBSs) based on diagnostic or therapeutic doses of I-131 can visualize metastatic lesions in thyroid cancer patients who have undergone total thyroidectomy. However, a variety of unusual lesions may cause false-positive results, and therefore, careful evaluation of abnormal scans is imperative to avoid unnecessary surgical removal or high-dose radioiodine treatment. Here, we report a patient with pulmonary aspergilloma mimicking metastasis of thyroid cancer on WBS. A 53-year-old woman with papillary thyroid cancer stage III (T1N1aM0) who had undergone total thyroidectomy and 150 mCi of radioiodine treatment for remnant ablation was found to have focal intense radioiodine accumulation in the left lung field by WBS, suggestive of pulmonary metastasis, at 5 days after I-131 administration. Whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and Tc-99m methoxyisobutyl isonitrile scans showed no remarkable tracer accumulation at the pulmonary nodule. An enhanced chest CT scan demonstrated a nonenhancing pulmonary nodule with an air-crescent sign suggestive of pulmonary fungus ball. A subsequent blood test for precipitating antibodies to Aspergillus antigens produced a result of 29.9 U/mL (reference range: 0-8 U/mL). The patient was clinically diagnosed as having pulmonary aspergilloma based on serologic test and radiologic imaging results. Extreme caution should be exercised when interpreting abnormal radioiodine WBS findings when the serum thyroglobulin is normal and imaging characteristics indicate a benign condition. Pulmonary aspergilloma is a cause of a false-positive lesion when radioiodine WBSs are performed.

Efficacy outcomes in a randomised trial of liposomal amphotericin B based on revised EORTC/MSG 2008 definitions of invasive mould disease

In 2008, the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) published revised definitions for diagnosing invasive fungal disease. A previous prospective trial of liposomal amphotericin B for invasive mould disease (AmBiLoad) used modified EORTC/MSG 2002 criteria. We wished to re-evaluate the response and survival based on the revised definitions to compare the outcomes of early vs. late treatment. Patients who had received an allogeneic haematopoietic stem cell transplant or who were neutropaenic (absolute neutrophil count <500 μl(-1) within 14 days of study entry) had been recruited on the basis of a halo or air crescent sign on chest computerised tomography. Originally classified as probable invasive mould disease, they were categorised as possible invasive mould disease using 2008 criteria. Patients had received liposomal amphotericin B at either 3 or 10 mg kg(-1) QD for 14 days, followed by 3 mg kg(-1) QD. Response at end of treatment and the 12-week survival were re-calculated according to 2008 definitions. Six-week survival was estimated by Kaplan-Meier analysis. Of 201 patients with invasive mould disease, 118 (59%) had a diagnosis based on halo signs (possible cases). Mycological evidence was present in 83 (41%) cases (probable/proven cases). Survival rates at 12 weeks for possible vs. probable/proven cases in the 3 mg kg(-1) QD group were 82% vs. 58% (P = 0.006), and 65% vs. 50% (P = 0.15) in the 10 mg kg(-1) QD group. At 6 weeks, rates were 87% vs. 69% in the 3 mg kg(-1) QD group (P = 0.009), and 75% vs. 61% in the 10 mg kg(-1) QD group (P = 0.01). Patients with possible invasive mould disease based on EORTC/MSG 2008 criteria had improved survival rates compared with those treated for probable/proven invasive mould disease. As possible invasive mould disease probably reflects an early-stage of disease, a better outcome might be expected when treatment with liposomal amphotericin B is started preemptively.

Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients

Invasive pulmonary aspergillosis (IPA) is an important cause of mortality in transplant recipients and in patients with neutropenia. Although IPA has been studied extensively in neutropenic patients, there are limited data on IPA in recipients of solid organ transplants (SOTs). We compared the clinical features and radiologic findings of 27 SOT recipients with IPA with those of 35 neutropenic patients with IPA. The SOT recipients were more likely than neutropenic patients to show peribronchial consolidation (31% vs. 7%; P=0.03) or ground-glass opacity (38% vs. 7%; P=0.007) and less likely to have fever (22% vs. 80%; P<0.001), macro-nodules (35% vs. 67%; P=0.02), mass-like consolidation (27% vs. 67%; P=0.004), halo signs (8% vs. 56%; P<0.001), or air-crescent signs (0% vs. 22%; P=0.01).

Clinical features of 32 cases of fungal pneumonia

A total of 32 patients with mycoses other than cavity-formed aspergilloma were reviewed. The main pathogenic fungi were Aspergillus in 14, Candida in 8, Cryptococcus in 4, Trichosporon in 4 and Mucor in 2. Coinfection by two species was detected in 3 cases: Trichosporon and Aspergillus in 2 and Aspergillus and Candida in 1. The underlying diseases were hematologic malignancies in all cases except 1 case of lung cancer. The hematologic malignancies were mostly leukemias of various types. Cryptococcosis developed in patients given long-term corticosteroid treatment but not in leukemic patients. All cases of aspergillosis, candidiasis and mucormycosis were due to nosocomial infection. On the other hand, 3 of 4 cases of cryptococcosis or trichosporonosis were attributable to community-acquired infection. Two of 4 trichosporonosis cases were considered to have been acquired during 2-day home stays. The diagnosis of pulmonary mycosis was made pathologically in 18 and clinically in 14 cases. Of the latter, 6 cases had an air-crescent sign on chest X-ray films and 8 cases were culture-positive. Extrapulmonary involvement was seen in all 16 cases of candidiasis, cryptococcosis and trichosporonosis but not in 10 of 14 aspergillosis cases. Severe granulocytopenia was present in all cases except 4 cases of cryptococcosis and 3 cases of aspergillosis. Chest X-ray findings of aspergillosis were of two types: one was an air-crescent sign which was noted in the recovery phase from leukopenia and the other was gradually enlarging consolidation which was bound by the interlobar fissure and progressed to lobar penumonia. A diffuse granular shadow was not characteristic of any fungus species.(ABSTRACT TRUNCATED AT 250 WORDS)

Pleomorphic Carcinoma with the Air-Crescent and CT Halo Signs: A Case Report

A pulmonary pleomorphic carcinoma is a rare, poorly differentiated, primary malignancy. We report an atypical manifestation of this rare tumor, with the air crescent and CT halo signs.

Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia.

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

Caspofungin for invasive aspergillosis: A single-centre prospective study

e20618 Background: Infections are the main complication for neutropenic patients (pts).Fungal infections represent a frequent cause of death. Caspofungin (Caspo) is the first drug able to inhibit the growth of the fungal cell wall. Methods: Since 2004 we began a prospective study with the administration of Caspo as first line therapy in 63 consecutive adult neutropenic pts. With persistent fever despite antibiotics,a chest CT-scan and galactomannan test were performed. In case of probable or proven infection Caspo was administered at the dose of 70 mg on the first day followed by 50 mg daily. They were 35 males and 28 females; the mean age was 56 yrs. The diagnoses were: leukemia 44, myeloma 3, lymphoma 16; the disease's phases were: new onset 24, remission 16, relapse 23. 12 pts received an allogeneic and 6 an autologous transplant; the others received conventional chemotherapy. Results: Fungal infections were proven in 12 and probable in 51 cases.The first site of infection was the lung in 62 pts. CT scan was positive(halo sign or air-crescent sign)in all the pts with a lung localization. BAL was performed in 37 pts.The mean time of treatment was 18 days. Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion were seen, and it was not necessary to administer any premedication. The global (partial and complete) response was 50/63 (79%); 13 pts died for fungal infection. The responses were generally similar for probable and proven infections. No breakthrough infections were seen. All surviving patients, upon discharge from the hospital, received oral treatment with voriconazole. For all the cured pts, there was a concomitant recovery of neutrophils and this seems crucial for the resolution of the infection. Among the 50 responsive patients, 25 died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 pts there was the recurrence of the fungal infection. Conclusions: The resolution rate of the infections is very high; Caspo seems safe, it does not preclude any other treatment, it is well tolerated and the cost is lower than other antifungal treatments. No significant financial relationships to disclose.

Signs in chest imaging: a pictorial review

A radiological sign can sometimes resemble a particular object or pattern and is often highly suggestive of a group of similar pathologies. Awareness of such similarities can shorten the differential diagnosis list. Many such signs have been described for X-ray and computed tomography (CT) images. In this article, we present the most frequently encountered plain film and CT signs in chest imaging. These signs include for plain films the air bronchogram sign, silhouette sign, deep sulcus sign, Continuous diaphragm sign, air crescent ("meniscus") sign, Golden S sign, cervicothoracic sign, Luftsichel sign, scimitar sign, doughnut sign, Hampton hump sign, Westermark sign, and juxtaphrenic peak sign, and for CT the gloved finger sign, CT halo sign, signet ring sign, comet tail sign, CT angiogram sign, crazy paving pattern, tree-in-bud sign, feeding vessel sign, split pleura sign, and reversed halo sign.

An Early CT-Diagnosis Based Treatment Strategy for Invasive Fungal Infection in Allogeneic Transplant Recipients Using Caspofungin First Line: An Effective Strategy with Low Mortality.

Empirical antifungal therapy is the standard treatment in allogeneic transplant patients who have persistent febrile neutropenia. This approach can be associated with increased cost, toxicity and breakthrough infections. There are limited reports to date of strategies for the early diagnosis of invasive fungal infection (IFI). These include either invasive investigations or serum testing. (Oshima K et al, J Antimicrobial Chemother 2007 Aug; 60(2): 350–5, Maertens J et al, Clin Infect Dis 2005; 41:1242–50). To our knowledge, there are no reports to date of treatment strategies based only on high resolution computerised tomography (HRCT) scans.We used a CT-diagnosis based treatment strategy for early invasive aspergillosis in 99 consecutive patients undergoing allogeneic transplantation over a two year time period. A retrospective review of the electronic patient record, notes and drug charts was undertaken in all patients receiving an allogeneic transplant in our unit from 1st January 2006 to 31st December 2007. The study protocol was approved by the Royal Marsden Hospital audit committee. Patients received primary antifungal prophylaxis with itraconazole or secondary prophylaxis with voriconazole from day + 1. Patients had a HRCT scan performed if they had antibiotic resistant fever for > 72 hours. Parenteral antifungal treatment with caspofungin was commenced in patients with a positive HRCT result. Cavitation, air crescent sign and halo sign were classified as major changes. Nodules and new infiltrates including consolidation and effusions were classified as minor changes. Serum testing was not used due to the possibility of false positive results with tazobactampiperacillin antimicrobials and low sensitivity in patients receiving mould active azoles as prophylaxis.Neutropenic fever developed in 89/99 patients (90%). Fifty-four percent (53/99) of patients developed antibiotic resistant fever for > 72 hours and would have received parenteral antifungal treatment if an empiric strategy had been used. The HRCT-based strategy reduced the use of parenteral antifungal treatment to 17% of patients (17/99). Four of these patients had engrafted (absolute neutrophil count >0.5x109 cells/L for 3 days) at time of commencing caspofungin following a period of persistent neutropenic fever. Fifteen patients had a positive HRCT scan and 2 were treated empirically until a HRCT could be performed. The remaining 36/53 patients (68%) did not receive antifungal treatment although they would have met criteria for standard empirical therapy. Our nonempiric strategy reduced the use of parenteral antifungal treatment from 54% to 17% of allogeneic transplant patients. These findings represent a 68% reduction in use of parenteral antifungal agentsCaspofungin (70mg once daily IV on day 1 and 50mg once daily IV thereafter) was given for a median of 13 days (3–34 days) and 11 patients responded to treatment. Six patients required second line antifungal therapy. Only one patient died from IFI after 100 days of follow-up. No patients had to stop caspofungin due to toxicity. Three of the 36 patients who did not receive initial antifungal treatment went on to receive empiric caspofungin within 100 days. One of these 3 patients died of enterococcal septicaemia. The other 2 patients recovered. None of this group had probable or proven IFI. During the extended follow-up period of 3–27 months (median 13 months) only 3/99 patients (3%) died of IFI.These results suggest that this non-empiric strategy of parenteral antifungal treatment based on HRCT scanning is feasible and may help to reduce toxicity, cost and breakthrough infections associated with the use of antifungal agents. Caspofungin may be a useful first line agent in this setting. A randomised controlled trial is warranted to further evaluate these results.

First Line Treatment of Probable and Proven Invasive Aspergillosis with Caspofungin in Oncohemopatic Patients. A Single Centre Experience

Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia. In particular fungal infections are the most difficult to treat and represent a major cause of mortality. Caspofungin (Caspo) is the first drug which is able to inhibit the growth of the fungal cell wall. Since January 2004 we have treated 64 consecutive adult neutropenic pts with Caspo as first line therapy. In the setting of persistent fever (3 days) despite broad spectrum antibiotic therapy and negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test were performed. In the setting of probable or proven fungal infection (according to the revised EORTC criteria and Cornely CID 2007) Caspo was administered at the dose of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. They were 35 males and 29 females; the mean age was 56 yrs (range 19–77 yrs). The diagnoses were: acute leukemia 46 (72%), myeloma 2 (3%), lymphoma 14 (22%) and chronic leukemia 2 (3%); the disease's phases were: new onset 26 (41%), remission 16 (24%), relapse 22 (35%). Thirteen pts received an allogeneic and 5 an autologous hematopoietic stem cell transplant; the other pts received an induction or consolidation or rescue chemotherapy course. Fungal infections were proven in 13 cases (20% including 11 aspergillus spp, 1 aspergillus fumigatus, 1 G. capitatum) and probable in 51 cases (80%). The first site of infection was the lung in 63 pts (98%) and paranasal sinuses in 1 patient (2%). CT scan was positive (halo sign or air-crescent sign) in all the pts with a lung localization, while the chest X-ray was positive in 40% of them. BAL was performed in 31 pts. The mean time of treatment was 18 days (range 13–25 days). Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion of Caspo were seen, and it was not necessary to administer any drug before the infusion as premedication. The global (partial and complete) response was 55/64 (86%); 9 pts died for fungal infection. The efficacy responses were generally similar for probable and proven infections. No breakthrough fungal infections were found. All surviving patients, upon discharge from the hospital, received oral treatment with Voriconazole or Posaconazole. For all the cured pts, there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial factor for the resolution of the infection. Among the 55 responsive patients, 25 (45%) died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 cases there was the recurrence of the fungal infection. In conclusion the resolution rate of the infections is very high (86%); Caspo seems safe, it does not preclude any other treatment (such as Cyclosporin A), it is well tolerated and the cost is lower than other antifungal treatments.

Pediatric Invasive Aspergillosis: A Multicenter Retrospective Analysis of 139 Contemporary Cases

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised children. Invasive aspergillosis has been well characterized in adults; however, the incidence and analysis of risk factors, diagnostic tools, treatments, and outcomes have not been well described for a large cohort of pediatric patients. We conducted the largest retrospective review of contemporary cases of proven and probable pediatric invasive aspergillosis diagnosed at 6 major medical centers (January 1, 2000, to July 1, 2005). Aspergillus fumigatus was the species most frequently recovered (52.8%) for the 139 patients analyzed. The majority of the children had a malignancy with or without hematopoietic stem cell transplant. Significant risk factors that impacted survival were immunosuppressive therapies and allogeneic stem cell transplant. The most common clinical site of invasive aspergillosis was the lungs (59%), and the most frequent diagnostic radiologic finding was nodules (34.6%). Only 2.2% of children showed the air crescent sign, 11% demonstrated the halo sign, and cavitation was seen in 24.5% of patients. Before the diagnosis of invasive aspergillosis, 43.1% of patients received fluconazole, and 39.2% received liposomal amphotericin B. After the diagnosis of invasive aspergillosis, 57% were treated with a lipid formulation of amphotericin B; however, 45.8% received > or = 3 concomitant antifungal agents. Analysis did not show superiority of any 1 antifungal related to overall mortality. A total of 52.5% (73 of 139) died during treatment for invasive aspergillosis. Of all the interventions implemented, surgery was the only independent predictor of survival. Our analyses revealed common findings between adult and pediatric invasive aspergillosis. However, one key difference is diagnostic radiologic findings. Unlike adults, children frequently do not manifest cavitation or the air crescent or halo signs, and this can significantly impact diagnosis. Immune reconstitution, rather than specific antifungal therapy, was found to be the best predictor of survival.

Changes in CT appearance of intrathoracic gossypiboma over 10 years

An intrathoracic gossypiboma is a rare condition. Moreover, intrathoracic gossypibomas with intrapulmonary location are extremely rare and only a few cases of intrapulmonary gossypiboma have been published. Usually gossypiboma has the characteristic CT appearance of a soft tissue mass with high attenuation, air bubbles and a whirl-like pattern, but its radiological manifestations may be variable according to the location and chronicity of the sponge. We report a case of intrathoracic gossypiboma initially misdiagnosed as an aspergilloma owing to its intrapulmonary location and air crescent sign on CT. In addition, our case will show morphological changes of the gossypiboma on CT during the 10 year follow-up period and correlate the CT findings with pathological results.

Adenocarcinoma of the Lung Presenting as a Mycetoma With an Air Crescent Sign

An 89-year-old man was admitted to the hospital due to intermittent anterior chest wall pain for > 1 month. A chest radiograph obtained on November 9, 2004, demonstrated a mass with an irregular border, inside a thin-walled cavity, located in the superior segment of the left lower lobe. A chest CT scan revealed an irregular thin-walled cavity, 5.9 x 5.4 x 4 cm in size, with an air-crescent sign in the superior segment of the left lower lobe, and an intracavitary fungus ball-like mass. A bronchoscopic examination was performed, revealing only external compression of the left lower lobe bronchial lumen. Cultures from both the brushing cytology and brushing fungus specimens were negative. Since the patient was a heavy smoker and the chest radiograph obtained 23 months before had revealed no active pulmonary lesion, neoplastic growth was still highly suspected. Thus, an (18)F-fluoro-2-deoxyglucose positron emission tomography study was performed on November 25, and a mass with a slightly increased standard uptake value (3.17; cutoff value, 2.5) was found. He received a left lower lobe lobectomy on December 23, and a tumor with many septum-like structures connecting the surrounding pulmonary parenchymal tissue was found in the superior segment of the left lower lobe. The final pathologic diagnosis was adenocarcinoma of the lung (pT2N0M0). Thus, even though the chest radiograph and chest CT scan showed a typical air-crescent sign (ie, mass inside a cavity) favoring a mycetoma, the physician should still keep in mind that lung cancer may also unusually present in this way.

Imaging Findings in Acute Invasive Pulmonary Aspergillosis: Clinical Significance of the Halo Sign

Computed tomography (CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which is an early sign of invasive pulmonary aspergillosis (IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life-threatening infection. Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings. At presentation, most patients (94%) had > or =1 macronodules, and many (61%) also had halo signs. Other imaging findings at presentation, including consolidations (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent signs (10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment (52% vs. 29%; P<.001) and greater survival to 84 days (71% vs. 53%; P<.01) than did patients who presented with other imaging findings. Most patients presented with a halo sign and/or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival.