Claus Peter Heussel

Treatment of fungal infections in hematology and oncology: Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

The Infectious Diseases Working Party of the German Society of Haematology and Oncology presents their guidelines for the treatment of fungal infections in patients with hematological and oncological malignancies. These guidelines are evidence-based, considering study results, case reports and expert opinions, using the evidence criteria of the Infectious Diseases Society of America (IDSA). The recommendations for major fungal complications in this setting are summarized here. The primary choice of therapy for chronic candidiasis should be fluconazole, reserving caspofungin or amphotericin B (AmB) for use in case of progression of the Candida infection. Patients with candidemia (except C. krusei or C. glabrata) who are in a clinically stable condition without previous azole prophylaxis should receive fluconazole, otherwise AmB or caspofungin. Voriconazole is recommended for the first-line treatment of invasive aspergillosis. The benefit of a combination of AmB and 5-flucytosine has not been demonstrated except in patients with cryptococcal meningitis. Mucormycosis is relatively rare. The drug therapy of choice consists of AmB, desoxycholate or liposomal formulation, in the highest tolerable dosage. Additional surgical intervention has been shown to achieve a lower fatality rate than with antifungal therapy alone. The role of interventional strategies, cytokines/G-CSF, and granulocyte transfusions in invasive fungal infections are further reviewed. These guidelines offer actual standards and discussions on the treatment of oropharyngeal and esophageal candidiasis, invasive candidiasis, cryptococcosis and mould infections.

Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients

Patients with severe neutropenia lasting for more than 10 days, who develop fever and pulmonary infiltrates, are at high risk of treatment failure and infection-related death, under conventional broad-spectrum antibiotics. Early supplementation by a systemic antifungal therapy active against Aspergillus spp. has been shown to markedly improve their clinical outcome. Prognosis is significantly influenced by early identification of lung infiltrates by means of high-resolution thoracic computed tomography. Non-culture based diagnostic procedures using a highly sensitive Sandwich ELISA assay to detect circulating galactomannan, or PCR techniques to amplify circulating fungal DNA, may facilitate the diagnosis of invasive pulmonary aspergillosis. CT-directed bronchoscopy and bronchoalveolar lavage using standardized procedures are useful in order to identify causative microorganisms such as filamentous fungi or Pneumocystis carinii. The standard antifungal agent in the treatment of these patients, amphotericin B deoxycholate, has been challenged recently by newly developed antifungals such as voriconazole. It seems important to continue antifungal treatment for at least 14 days before first response assessment. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates, to avoid inadequate antimicrobial treatment modification.

Diagnosis of invasive fungal infections in hematology and oncology--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation empirical antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.

Diagnosis of invasive fungal infections in hematology and oncology—guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO)

Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either empirical or preemptive antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

CT attenuation of paired HRCT scans obtained at full inspiratory/expiratory position: comparison with pulmonary function tests

Abstract. The purpose of this prospective study was to measure lung attenuation at paired HRCT obtained at full inspiratory/expiratory position, to correlate with pulmonary function tests (PFTs) and to characterize different types of ventilatory impairment. One hundred fifty-five patients with and without pulmonary disease underwent paired HRCT obtained at full inspiratory/expiratory position. Three scan pairs were evaluated by densito- and planimetry using dedicated software. The PFTs were available for correlation in all patients (mean interval 5xa0days). Mean lung density (MLD) at full inspiration was –813xa0HU, and MLD at full expiration was –736xa0HU; both, as well as the expiratory attenuation increase, demonstrated significant correlations with static and dynamic lung volumes: up to r=0.68, p<0.05 for residual volume. The MLD and emphysema indices correlated markedly better for scans obtained at full expiration than at full inspiration, e.g. correlation with the residual volume: r=0.68 compared with r=0.55. Even better correlations were obtained for the lung area (229xa0cm2 at inspiration, 190xa0cm2 at expiration), up to r=0.74 for the lung area in expiration and the intrathoracic gas volume. Inspiratory MLD and the expiratory attenuation increase were able to differentiate obstructive and restrictive ventilatory impairment from normal subjects, the best results were obtained from scans obtained at full expiratory position (p<0.05). In conclusion, scans obtained at full expiratory position reveal more functional information than scans obtained at full inspiratory position. Quantitative analysis of CT obtained at full expiratory position provides good estimations of static and dynamic lung volumes as well as significant differences between normal subjects and patients with ventilatory impairment.

Value of contrast-enhanced MR angiography and helical CT angiography in chronic thromboembolic pulmonary hypertension.

The aim of this study was to evaluate the diagnostic value of contrast-enhanced MR angiography (ce MRA) and helical CT angiography (CTA) of the pulmonary arteries in the preoperative workup of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The ce MRA and CTA studies of 32 patients were included in this retrospective evaluation. Image quality was scored by two independent blinded observers. Data sets were assessed for number of patent segmental, subsegmental arteries, and number of vascular segments with thrombotic wall thickening, intraluminal webs, and abnormal proximal to distal tapering. Image quality for MRA/CTA was scored excellent in 16 of 16, good in 11 of 14, moderate in 2 of 5, and poor in no examinations. The MRA/CTA showed 357 of 366 patent segmental and 627 of 834 patent subsegmental arteries. CTA was superior to MRA in visualization of thrombotic wall thickening (339 vs 164) and of intraluminal webs (257 vs 162). Abnormal proximal to distal tapering was better assessed by MRA than CTA (189 vs 16). In joint assessment of direct and indirect signs, MRA and CTA were equally effective (353 vs 355). MRA and CTA are equally effective in the detection of segmental occlusions of the pulmonary arteries in CTEPH. CTA is superior for the depiction of patent subsegmental arteries, of intraluminal webs, and for the direct demonstration of thrombotic wall thickening.

Dynamic 19F-MRI of pulmonary ventilation using sulfur hexafluoride (SF6) gas

A new method for dynamic imaging of pulmonary wash‐in and wash‐out kinetics of inhaled sulfur hexafluoride (SF6) gas was developed. Measurements at the fluorine‐19 Larmor frequency were performed in pigs using a gradient echo pulse sequence with 0.5 ms echo time and a measurement time of 9.1 s per image. Dynamic MRI was performed during wash‐in and wash‐out of SF6 gas in mechanically ventilated porcine lungs. A postprocessing strategy was developed for quantitative determination of wash‐out time constants in the presence of noise. Mean wash‐out constants were 4.78 ± 0.48 breaths vs. 4.33 ± 0.76 breaths for left and right lung when ventilation was performed with low tidal volume, and 1.73 ± 0.16 breaths vs. 1.85 ± 0.11 breaths with high tidal volume ventilation. In conclusion, breath‐hold MRI of SF6 gas is feasible in large animals. Moreover, regional wash‐in and wash‐out kinetics of SF6 can be determined noninvasively with this new method. Potential human applications are discussed. Magn Reson Med 45:605–613, 2001.

Hybrid segmentation and exploration of the human lungs

Segmentation of the tracheo-bronchial tree of the lungs is notoriously difficult. This is due to the fact that the small size of some of the anatomical structures is subject to partial volume effects. Furthermore, the limited intensity contrast between the participating materials (air, blood, and tissue) increases the segmentation of difficulties. In this paper, we propose a hybrid segmentation method which is based on a pipeline of three segmentation stages to extract the lower airways down to the seventh generation of the bronchi. User interaction is limited to the specification of a seed point inside the easily detectable trachea at the upper end of the lower airways. Similarly, the complementary vascular tree of the lungs can be segmented. Furthermore, we modified our virtual endoscopy system to visualize the vascular and airway system of the lungs along with other features, such as lung tumors.

Assessment of lung microstructure with magnetic resonance imaging of hyperpolarized Helium-3☆

Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are shown.

3He-MRI in follow-up of lung transplant recipients

The aim of this study was to evaluate the possible contribution of 3He-MRI to detect obliterative bronchiolitis (OB) in the follow-up of lung transplant recipients. Nine single- and double-lung transplanted patients were studied by an initial and a follow-up 3He-MRI study. Images were evaluated subjectively by estimation of ventilation defect area and quantitatively by individually adapted threshold segmentation and subsequent calculation of ventilated lung volume. Bronchiolitis obliterans syndrome (BOS) was diagnosed using pulmonary function tests. At 3He-MRI, OB was suspected if ventilated lung volume had decreased by 10% or more at the follow-up MRI study compared with the initial study. General accordance between pulmonary function testing and 3He-MRI was good, although subjective evaluation of 3He-MRI underestimated improvement in ventilation as obtained by pulmonary function tests. The 3He-MRI indicated OB in 6 cases. According to pulmonary function tests, BOS was diagnosed in 5 cases. All diagnoses of BOS were also detected by 3He-MRI. In 2 of these 5 cases, 3He-MRI indicated OB earlier than pulmonary function tests. The results support the hypothesis that 3He-MRI may be sensitive for early detection of OB and emphasize the need for larger prospective follow-up studies.