Our 2015 approach to invasive pulmonary aspergillosis.

At the University Hospital of Cologne, in general two patient groups at high risk for invasive aspergillosis receive posaconazole prophylaxis: Acute myelogenous leukaemia patients during remission induction chemotherapy and allogeneic haematopoietic stem cell transplant recipients. Other patients at risk undergo serum galactomannan testing three times weekly. At 72-96 h of persisting fever despite broad-spectrum antibiotics, or at onset of lower respiratory tract symptoms a thoracic computed tomography (CT) scan is performed. Without lung infiltrates on CT, IPA is ruled out. In lung infiltrates not suggestive for IPA mycological confirmation is pursued. In patients without posaconazole prophylaxis empiric caspofungin will be considered. CT findings typical for IPA prompt targeted treatment, and mycological confirmation. Bronchoalveolar lavage (BAL) is most important for cultural identification and susceptibility testing, and facilitates diagnosing other pathogens. BAL performance is virtually independent of platelet counts. If despite suggestive infiltrates BAL does not yield the diagnosis, CT-guided biopsy follows as soon as platelet counts allow. Surgery can also be beneficial in diagnosis and treatment of IPA. If the diagnosis of IPA is not established, mucormycosis is a valid concern. In patients with breakthrough IPA during posaconazole prophylaxis liposomal amphotericin B is the drug of choice. If no posaconazole prophylaxis was given, voriconazole is the treatment of choice for IPA.

[Chronic pulmonary Aspergillosis. Four exemplary clinical cases and literature overview]. / Chronische pulmonale Aspergillose. Vier klinische Fallbeispiele und Überblick über die aktuelle Literatur.

Chronic pulmonary aspergillosis (CPA) is a rare complication in patients with either mild immunosuppression or various pulmonary diseases. Diagnosis and therapy are challenging because of unspecific symptoms like productive cough, weight loss, fever and haemoptysis. Differential diagnoses are manifold, and CPA is characterized by findings in chest CT and serologic proof of precipitins. Surgery is only recommended for simple aspergillomas. Recurrent prolonged courses of antifungal treatment yield satisfactory short-term outcome, but long-term prognosis is uncertain. We provide an overview of the literature and present four cases to illustrate disease diversity.

Chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a group of consuming diseases usually presenting with prolonged and relapsing cough, dyspnoea and weight loss. Acute symptoms such as haemoptysis and bronchial or pulmonary haemorrhage may occasionally occur. CPA affects patients with underlying pulmonary conditions, for example, chronic obstructive pulmonary disease or mycobacteriosis or common immunosuppressive conditions such as diabetes. Precise epidemiology is unknown, and while prevalence is considered low the chronic and relapsing nature of the disease challenges the treating physician. Diagnostics largely rely on serologic Aspergillus precipitins and findings on thoracic computed tomography. The latter are manifold comprising cavity formation, pleural involvement and sometimes aspergilloma. Other markers for aspergillosis are less helpful, in part due to the non- or semi-invasive nature of these forms of Aspergillus infection. Various antifungals were shown to be effective in CPA treatment. Azoles are the most frequently applied antifungals in the outpatient setting, but are now compromised by findings of Aspergillus resistance. Long-term prognosis is not fully elucidated and may be driven by the underlying morbidities. Prospective registry-type studies may be suitable to systematically broaden our CPA knowledge base. This article gives an overview of the available literature and proposes a clinical working algorithm for CPA management.

[Experiences with power-injectable port systems: complications, patient satisfaction and clinical benefit]. / Komplikationsrate, Patientenzufriedenheit und klinischer Einsatz nach Implantation eines Portkathetersystems mit Zulassung zur Hochdruckinfusion.

PURPOSE: Evaluation of complications, patient satisfaction and clinical benefit of port systems with authorization for high pressure injection of contrast agent during CT/MR examinations. MATERIALS AND METHODS: Ultrasound-guided insertions of central venous port catheters were performed through the lateral subclavian vein at a university teaching hospital. The radiological information system (HIS/RIS) was used to evaluate technical success and complication rates. Assessment of patient satisfaction and clinical benefit was carried out by a questionnaire during a telephone call 6 months after implantation of the port system. RESULTS: A total of 195 port systems in 193 patients were implanted. The catheter remained in place for a mean duration of 169 days (overall 29,210 catheter days). The technical success rate was 99.5 % and the overall complication rate was 17.4 % (24/138; 0.82 per 1000 catheter days). Follow-up revealed 13 early port explantations (9 %). Most of the patients reported high satisfaction in general (satisfied/very satisfied: 94 %). 34/209 contrast-enhanced CT/MRT scans (16 %) were performed using the port for contrast media injection. There were no complications during or after administration of contrast agent via the port system. CONCLUSION: The Powerport system is a safe alternative for peripheral i. v. contrast media injection during CT/MR scans, but has been infrequently used. Most patients reported high overall satisfaction with the port system.

[Misplacement of central venous catheters in the subclavian artery: safe retrieval with a percutaneous closure device (AngioSeal)]. / Fehllage zentraler Venenkatheter in der Arteria subclavia: zuverlässige Entfernung mit einem perkutanen Verschlusssystem (AngioSeal).

PURPOSE: To evaluate the feasibility of retrieval of misplaced central venous catheters in the subclavian artery with a percutaneous closure device (AngioSeal). MATERIALS AND METHODS: According to the radiologic information system of a university hospital, 7 patients (6 women, 1 child) underwent removal of a misplaced central venous catheter (4 × 7 F, 1 × 8 F, 2 × 13 F) in the subclavian artery between January 2008 and June 2012 with the 8 F percutaneous closure device AngioSeal. The body mass index (BMI) of 7 patients was available, 3 of whom were obese (BMI 2 × 35.7 and 1 × 33.0). Both 13 F catheters were removed in a balloon-supported manner as described elsewhere. The Broviak catheter of a 21-month-old boy was removed by surgical support with preparation of the catheter to its vessel entry. Success control was done by a transfemoral DSA in 5 of the 7 patients. 2 patients received clinical follow-up. RESULTS: In all cases the misplaced catheter could be removed successfully. In all 7 patients, there was no arterial bleeding after catheter removal. Complications were not observed. CONCLUSION: Removal of misplaced central venous catheters in the subclavian artery by the percutaneous closure device AngioSeal is safe. Percutaneous catheter removal should be regarded as the method of choice, even in obese patients.

Looking for landmarks in medial orbital trauma surgery.

Knowledge of the precise location of anatomical landmarks such as the anterior (AEC) and posterior ethmoid (PEC) canals facilitates medial orbital wall surgery and is of major importance for the protection of the orbital nerve. The aim of this study was to identify these anatomical structures in 100 consecutive CT scans and measure the distance between them. The authors investigated whether a predictable symmetry existed between the left and right side. The AEC was not identified unilaterally in one patient, the PEC was not identified unilaterally in six patients and not bilaterally in one patient. An additional PEC was found unilaterally in 12 and bilaterally in five patients. If an anatomical structure was found bilaterally, the authors obtained a strong Pearson's correlation between the sides (r=0.798-0.903, p<0.001). An anatomical variation was found in nearly every fourth patient. The authors think that these data call into question the use of the PEC and AEC as reliable surgical landmarks in medial orbital surgery.

CT coronary angiography: coronary CT-flow quantification supplements morphological stenosis analysis.

BACKGROUND: Our rationale was to evaluate whether a 64-slice CT scanner allows accurate measurement of computed tomographic (CT) changes in coronary artery flow profiles and whether CT flow measurements are suitable for classifying the significance and hemodynamic relevance of a stenosis and thereby supplement as a functional parameter for morphological stenosis analysis. METHODS: A total of 50 patients prospectively underwent computed tomography coronary angiography (coronary CTA) in a multidetector CT scanner (Brilliance 64, Philips)±1 day before or after invasive coronary angiography (ICA). Immediately thereafter, 2 radiologists reviewed the imaging data to detect any vessel segments with morphology poorly evaluable by coronary CTA. A locally constant cyclical measurement was acquired in these coronary arteries in breath-hold technique during the passage of a 50ml bolus of contrast media. For analysis, time-density curves of the bolus passage were registered in the coronary artery and the aorta (internal reference), the up-slopes were determined and correlated with each other. The results were compared with the ICA findings. RESULTS: 47 of 50 CT flow measurements were evaluable. A good correlation was found between the degrees of stenosis and slope ratios in aorta and coronary artery (R(2)=0.92). The threshold corridor was 0.55-0.77 for distinguishing hemodynamically (≥70%) from non-hemodynamically relevant stenoses. CONCLUSIONS: CT-based coronary artery flow measurements (CTFM) correlate well with the angiographically determined degree of stenosis and can elevate by non-invasive means the diagnostic accuracy of coronary CTA. From both a clinically diagnostic and scientific standpoint, CTFM proves a suitable method for quantifying coronary blood flow.

Association of transcobalamin c. 776C>G with overall survival in patients with primary central nervous system lymphoma.

BACKGROUND: Chemotherapy for primary central nervous system lymphoma (PCNSL) is based on methotrexate (MTX), which interferes with both nucleic acid synthesis and methionine metabolism. We have reported previously that genetic variants with influence on methionine metabolism are associated with MTX side effects, that is, the occurrence of white matter lesions as a sign of MTX neurotoxicity. Here, we investigated whether such variants are associated with MTX efficacy in terms of overall survival in MTX-treated PCNSL patients. METHODS: We analysed seven genetic variants influencing methionine metabolism in 68 PCNSL patients treated with systemic and facultative intraventricular MTX-based polychemotherapy (Bonn protocol). RESULTS: Median age at diagnosis was 59 years (range: 28-77), 32 patients were female. Younger age (Wald=8.9; P=0.003) and the wild-type C (CC) allele of the genotype transcobalamin c (Tc2). 776C>G (Wald=6.7; P=0.010) were associated with longer overall survival in a multivariate COX regression analysis. CONCLUSION: This observation suggests that the missense variant Tc2. 776C>G influences both neurotoxicity and efficacy of MTX in the Bonn PCNSL protocol.

Quality control of involved-field radiotherapy for patients with early stage Hodgkin's lymphoma based on a central prospective review. Comparison of the results between two study generations of the German Hodgkin Study Group.

PURPOSE: Based on experience in trials HD10 and HD11 (1998-2003), the radiotherapy reference center of the German Hodgkin Study Group (GHSG) continued their central prospective radiation oncological review in trials HD13 and HD14. The purpose of this analysis was to identify the impact of this procedure on radiotherapeutic management and to compare findings with former trials. METHODS: Between 2003 and 2009, 1,710 patients were enrolled in the HD13 trial (early favorable stages) and 2,039 patients in the HD14 trial (early unfavorable stages). All patients received a total of 30 Gy involved-field (IF) radiotherapy within a combined modality approach. RESULTS: For patients in HD13, there was a correction of disease involvement in 847/1,518 patients (56%), and for patients in HD14 in 1,370/1,905 patients (72%). Most discrepancies were observed in the lower mediastinum (19.2%), infraclavicular (31.7%), upper cervical (12.7%), and supraclavicular (10.8%) lymph nodes. This resulted in a change of disease stage in 241 (7%) patients and a shift into another study protocol in 66 (2%) patients. Due to the incorrect lymph node documentation of the participating study centers, the IF radiotherapy volume had to be enlarged in 1,063/3,423 patients (31%) and reduced in 244/3,423 patients (7.1%). These findings are comparable to the results of the quality control in the trials HD10 and HD11 (2,611 patients reviewed). CONCLUSION: Central review of the diagnostic imaging and clinical findings of Hodgkin's lymphoma patients shows a considerable number of discrepancies compared with the local evaluation. Thus, meticulous evaluation of all imaging information in close collaboration between the radiation oncologist and diagnostic radiologist is mandatory.

Pandemic 2009 influenza A(H1N1) virus infection coinciding with invasive pulmonary aspergillosis in neutropenic patients.

SIn patients receiving anti-neoplastic chemotherapy, the impact of influenza on the incidence of invasive pulmonary aspergillosis (IPA) remains unknown. We matched data of the Cologne Cohort of Neutropenic Patients (CoCoNut) with records from the Institute for Virology and compared the findings to historical data. During the pandemic, we diagnosed influenza A(H1N1) in five patients with malignancies and febrile neutropenia refractory to antibiotic therapy. Probable IPA was diagnosed in three of these patients on the grounds of typical computed tomography morphology and microbiological results. Three of five patients receiving remission-induction chemotherapy for acute myeloid leukaemia developed aspergillosis although receiving posaconazole prophylaxis. In the 3 years before the influenza pandemic, only 2/77 patients of this group developed infection. Infection with influenza A(H1N1) may increase the risk for invasive aspergillosis in neutropenic patients. Pulmonary aspergillosis is an important additional differential diagnosis in neutropenic influenza patients with pneumonia.

[Radiofrequency of the liver - an update]. / Radiofrequenzablation der Leber - eine aktuelle Übersicht.

The impact of radiofrequency ablation (RFA) as a local ablative tumor therapy is increasing. Randomized trials justify RFA for small hepatocellular carcinoma (HCC) (single tumor ≤ 5 cm or three or less tumors ≤ 3 cm). Surgical resection still remains the gold standard for resectable colorectal liver metastases (CRLM). Several single center trials demonstrate improved patient survival by RFA and justify RFA for non-resectable CRLM. Local recurrence increases significantly with tumor diameters > 3 cm. There is insufficient evidence at this time to resolve the issue of optimal approach for treatment of CRLM. Technical development of the electrode design, improved ablation algorithms, and simplification of the exact electrode placement by new real-time fusion techniques of pre-interventional CT or MRT images with intra-interventional ultrasound have the potential to reduce the variable and sometimes high rate of local tumor recurrence. The clinical impact of immunological aspects following RFA with regard to patient survival and local tumor recurrence remains unclear.

Clinical effectiveness of posaconazole prophylaxis in patients with acute myelogenous leukaemia (AML): a 6 year experience of the Cologne AML cohort.

BACKGROUND: Large randomized controlled trials have shown significant decreases in morbidity and mortality in leukaemia patients with posaconazole prophylaxis. However, the value of prophylaxis has been questioned in centres with a low incidence of invasive fungal diseases (IFDs) and pre-emptive treatment strategies. METHODS: We prospectively evaluated the epidemiology of IFDs in acute myelogenous leukaemia (AML) patients undergoing first remission-induction chemotherapy before and after posaconazole prophylaxis had been introduced as a standard of care. Patients admitted from January 2003 to December 2005 received topical polyenes as antifungal prophylaxis (first group), while those admitted between January 2006 and December 2008 received 200 mg of oral posaconazole three times daily (second group). Other diagnostic and therapeutic standard operating procedures remained unchanged. RESULTS: A total of 82 patients in the polyene prophylaxis group and 77 in the posaconazole prophylaxis group were included in the final analysis. Baseline characteristics were well matched between groups. Patients receiving topical polyene prophylaxis were more likely to experience breakthrough IFDs (19.5% and 3.9%; P = 0.003) or breakthrough aspergillosis (13.4% and 2.6%; P = 0.018) than patients receiving systemic posaconazole prophylaxis. They also had more febrile days (mean 10.7 +/- 9.66 and 7.3 +/- 5.73; P = 0.007), longer need for inpatient treatment (mean 53.0 +/- 24.16 and 46.0 +/- 14.39; P = 0.026) and a shorter fungal-free survival (78.7 and 90.4 days; P = 0.024). No significant differences were observed for persistent fever, pneumonia, lung infiltrates indicative of invasive pulmonary aspergillosis, or attributable and overall mortality. CONCLUSIONS: After introduction of posaconazole prophylaxis for patients with AML, the number of febrile days, the incidence rate of IFDs and aspergillosis and the duration of hospitalization decreased significantly.

Electro-physiological parameters of hepatic radiofrequency ablation--a comparison of an in vitro versus an in vivo porcine liver model.

BACKGROUND: Radiofrequency ablation (RFA) is an inherent part of curative treatment within a multimodal therapy concept of malignant liver tumors. The biggest problem is the high rate of local recurrences in tumors with a diameter of more than 3 cm because of the high variability and poor reproducibility of the zone of ablation. No imaging modality facilitates monitoring during neither intraoperativ nor percutaneous RFA. This experimental study describes and compares an in vitro and in vivo porcine model by its electro-physiological parameters with the aim of monitoring RFA procedures. MATERIALS AND METHODS: RFA was performed in a perfused in vitro porcine (one RFA per liver) and in vivo porcine model (24 animals) with three different RFA systems (Rita XL 5 cm, Rita XLi 7 cm, LeVeen 5 cm). In the in vivo model, percutaneous placement of the RFA device was guided by native and contrast-enhanced CT scan. The electro-physical parameters during RFA were online (in real time) recorded by a dedicated software. After the RFA, the livers were explanted, sliced, and measured according to the consensus technique. RESULTS: The delivered energy was in vivo versus in vitro: Rita XL 238 +/- 135 kJ versus 135 +/- 53 kJ (p = 0.247); Rita XLi 711 +/- 180 kJ versus 159 +/- 54 (p = 0.016) and with LeVeen 212 +/- 71 kJ (in vivo). The LeVeen system was inconsistent in the in vitro model. This correlates to an energy consumption per ml of necrosis in vivo versus in vitro Rita XL of 8 +/- 3 kJ/ml versus 6.4 +/- 3.9 kJ/ml (p = 0.537), Rita XLi of 10 +/- 6 kJ/ml versus 1.8 +/- 0.2 kJ/ml (p = 0.016), and LeVeen of 14.0 +/- 12 kJ/ml (in vivo). The volume of ablation was in vivo versus in vitro Rita XL 30 +/- 10 ml versus 26 +/- 17 ml (p = 0.329), Rita XLi 90 +/- 58 ml versus 88 +/- 21 ml (p = 0.905), and LeVeen 22 +/- 11 ml versus 50 +/- 12 ml (p = 0.04). The impedance during RFA were in vivo versus in vitro Rita XL 39 +/- 4 Omega versus 50 +/- 14 Omega (p < 0.247), Rita XLi 33 +/- 5 Omega versus 61 +/- 16 Omega (p = 0.016) and LeVeen 31 +/- 2 Omega (in vivo). CONCLUSION: The volume of ablation showed analogue data in vivo and in vitro. The delivered energy and energy consumption was in vivo up to five times (Rita XLi) higher than in vitro and the impedance in vivo was always lower than in vitro. These differences observed between in vivo and in vitro were more pronounced than previously described. Thus the use of an in vitro model for research of the RFA technique must be challenged. The large deployment of the Rita XLi was a problem for percutaneous positioning of the device without direct contact to liver surface or major vessels in 80-kg pigs and to a lesser extent in in vitro liver originating from 130- to 140-kg pigs. Modern RFA systems which generate large volume of tissue necrosis can therefore only be adequately tested in a porcine model with a liver weight of at least 1.5-2 kg. Alternatively, a bovine liver model (with a liver weight up to 10 kg) should be developed in the future.