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Background and Objective: The exact timing of the evolution of lesion volumes of invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the management of hematological patients but has never been evaluated in a prospective study. We analyzed the CT scan data from the prospective Combistrat trial., Design and Methods: Volumes of aspergillosis lesions from 30 patients (including 24 acute myeloid leukaemia) with probable (n=26) or proven (n=4) IPA according to the EORTC-MSG modified criteria, were measured prospectively on the thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of treatment (EOT)., Results: For the overall population, the volume of pulmonary aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p=0.003). Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with p=0.003 for D14 vs. D7, but with p=0.56 for D14 vs. D0). At EOT (= D17, median value), the volume of lesions was significantly lower than D14 (0.76 fold the initial volume; p<0.001) but it was not significantly different when compared to D0 (p=0.11)., Conclusions: The results of this prospective study suggest that the sequential analysis of CT scan in neutropenic patients with IPA depicts more precisely the evolution of lesion volumes than comparison to baseline images. Moreover, the systematic use of chest CT appears to be a useful tool for diagnosis and outcome evaluation of IPA in clinical trials., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Invasive pulmonary aspergillosis (IPA) occurs mostly in immunocompromised hosts and especially in neutropenic patients. Improved prognosis for IPA requires early diagnosis. We report our experience in the management of IPA in patients with hematological malignancies. In prolonged neutropenia (> 10 days), thoracic CT scanning seems to be the best choice for the diagnosis of IPA (with CT halo or air-crescent signs). Its systematic use allows a dramatic reduction in the time to achieve the diagnosis, if there is evidence of a halo sign. The systematic screening for the detection of Aspergillus antigenemia with an ELISA test is helpful for early diagnosis. The detection of Aspergillus antigen (with the less sensitive latex agglutination test) on bronchoalveolar lavage (BAL) fluid may also be as useful. The treatment of IPA relies on amphotericin B (or its lipid formulations) or on azole antifungal agents. Pulmonary surgical resection should be considered either as an emergency procedure (despite persistent neutropenia) to avoid massive hemoptysis, or as an elective or diagnostic procedure. This global strategy for the management of IPA is associated with a 75-80% success rate in hematological patients. Nevertheless, the control of underlying malignancy remains a major prognostic factor.

Purpose: In patients with neutropenia, thoracic computed tomography (CT) halo and air-crescent signs are recognized as major indicators of invasive pulmonary aspergillosis (IPA). Nevertheless, the exact timing of CT images is not well known., Patients and Methods: Seventy-one thoracic CT scans were analyzed in 25 patients with neutropenia with surgically proven IPA., Results: On the first day of IPA diagnosis with early CT scan (d0), a typical CT halo sign was observed in 24 of 25 patients. At that time, the median number of thoracic lesions was two (range, one to six), and pulmonary involvement was bilateral in 12 cases. The halo sign was present in 68%, 22%, and 19% of cases on d3, d7, and d14, respectively. Similarly, the air-crescent sign was seen in 8%, 28%, and 63% of cases on the same days. Otherwise, a nonspecific air-space consolidation aspect was seen in 31%, 50%, and 18% of cases on the same days. The analysis of calculated aspergillary volumes on CT showed that, despite antifungal treatment, the median volume of lesions increased four-fold from d0 to d7, whereas it remained stable from d7 to d14. Overall, 21 patients (84%) were cured by the medical-surgical approach., Conclusion: In patients with neutropenia, CT halo sign is a highly effective modality for IPA diagnosis. The duration of the halo sign is short, and it demonstrates the value of early CT. The increase of the aspergillosis size on CT in the first days after IPA diagnosis is not correlated with a pejorative immediate outcome when using a combined medical-surgical approach.

The aim of the study is to specify the indication for surgery in the treatment of invasive pulmonary aspergillosis (API). From January 1991 to October 1996 nineteen patients who had been treated with chemotherapy and associated marrow aplasia and suffering from API were operated on. At the time of the surgical intervention all of the patients were treated with antifungal drugs. The delay between the start of their symptoms and the start of treatment was 2.6 days (range: 0-17 days). 1. The risk of a massive haemoptysis by contact between the fungal infection and the pulmonary artery led to eight urgent surgical operations: six lobectomies and two lobectomies associated with segmentectomy. The mean level of polymorphonuclear neutrophils was 296 cell/mm3 (0-1,000). Plastic surgery on the pulmonary artery was carried out in three patients. One patient died after the operation with progression of the API. The duration of postoperative stay was 13 days (6-18). 2. Planned surgery consisted of a resection of the residual mass after antifungal treatment and a diagnostic approach to the intraparenchymatous mass of indeterminate aetiology. A resection of the residual masses (in spite of antifungal treatment) was carried out in seven patients: before further haematological therapy in six cases and in one case for a superinfected lesion. The type of resection was: a lobectomy (n = 4), a lingulectomy (n = 1) and an atypical resection (n = 2). No postoperative deaths were reported. The patients left the surgical service between the seventh and twentieth day postoperatively. The surgery was used in four patients as the diagnostic approach in view of intraparenchymal masses of unknown aetiology and had enabled a fungal mycelium to be isolated at the centre of persisting inflammation. Antifungal treatment sometimes associated with surgery allowed for a better prognosis in patients suffering from invasive pulmonary aspergillosis.

Background: The aim of our study was to clarify the indications for operation in invasive pulmonary aspergillosis., Methods: Nineteen patients with hematologic malignancy, in whom invasive pulmonary aspergillosis developed during the course of neutropenia, had operations. Neutropenia lasted 28 days (range, 15 to 45 days). The preoperative diagnosis of invasive pulmonary aspergillosis was based on computed tomographic scan findings (halo or air crescent signs)., Results: Eight patients underwent emergency operations, before marrow recovery, for prevention of massive hemoptysis. The criterion for operation was an aspergillosis lesion that contacted the pulmonary artery on computed tomography. A lobectomy was performed in all cases. A sleeve resection of the pulmonary artery was necessary on two occasions. There was one postoperative death due to extensive aspergillosis. The length of hospitalization after operation was 13 days (range, 6 to 18 days). Seven patients were treated by elective resection of a residual mass (before hematologic therapy in 6 cases). The types of resection performed were lobectomy (n = 4), lingulectomy (n = 1), and wedge resection (n = 2). There were no postoperative deaths. The average length of stay before discharge from the hospital was 11 days (range, 7 to 20 days). The surgical resection was performed as a diagnostic procedure in the 4 remaining patients after an allotted time of 14 days (range, 4 to 24 days) from initiation of antifungal therapy., Conclusions: The combination of antifungal agents and surgical resection is an efficient strategy for the treatment of invasive pulmonary aspergillosis in patients with hematologic malignancy.

Purpose: The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients., Patients and Methods: Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively., Results: The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value < 9 g/L were associated with better outcome., Conclusion: In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.

In neutropenic patients, one way of improving invasive pulmonary aspergillosis (IPA) prognosis is an earlier initiation of the antifungal treatment. We report our experience with 36 cases of IPA in 35 patients with haematological malignancies. When aspergillosis was diagnosed, all but 2 patients were neutropenic (PMN < 500; median duration = 20 days). The most frequent clinical signs were cough (100%), chest pain (78%) and haemoptysis (58%). Before the diagnosis of IPA, Aspergillus antibody test was positive in 60% of cases. A thoracic CT-scan was performed in 23 patients and demonstrated highly suggestive images in 22 cases (96%) with presence of CT halo sign (n = 13) or CT air-crescent sign (n = 9). Moreover, Aspergillus antigen test was positive in 13 of 28 tested patients. IPA diagnosis was determined to be definite in 23 cases and probable or possible in 13 cases. Thirty-five patients were treated: in 3 cases with amphotericin B (2 failures) and in 32 cases with itraconazole (7 failures and 25 successes or improvements). In 7 cases (including 5 emergencies) surgical resection was successfully combined with the medical treatment. In neutropenic patients with fever, we consider that thoracic CT-scan and repeated biological tests (Aspergillus antibody and antigen tests) can be used to establish the diagnosis of aspergillosis. Early treatment with itraconazole and surgical resection appears to improve prognosis.