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1.  Does volume perfusion computed tomography enable differentiation of metastatic and non-metastatic mediastinal lymph nodes in lung cancer patients? A feasibility study 
Cancer Imaging  2013;13(3):323-331.
Objectives: To compare the perfusion characteristics of mediastinal lymph node metastases with those of non-metastatic nodes in patients with newly diagnosed lung cancer using volume perfusion computed tomography (VPCT). Materials and methods: Between January 2010 and October 2011, 101 patients with histologically confirmed, untreated lung cancer received a 40-s VPCT of the tumor bulk; 32/101 patients had evident hilar/mediastinal metastatic disease and 17/101 patients had proven non-metastasized lymph nodes within the VPCT scan range. Validation or exclusion of metastatic node involvement was proven by mediastinoscopy, biopsy, positron emission tomography imaging and/or unequivocal volume dynamics on follow-up computed tomography. A total of 45 metastases and 23 non-metastatic lymph nodes were found within the scan range and subsequently evaluated. Blood flow (BF), blood volume (BV) and Ktrans were determined. Tumor volume was recorded as whole tumor volume. Results: In a comparison between metastatic and non-metastatic lymph nodes, we controlled for age, lymph node volume, lung tumor volume, lung tumor location, and histologic type effects and found no significant differences with respect to BF, BV, Ktrans or heterogeneity in nodal perfusion (P > 0.05, respectively), even after adjusting lymph node perfusion values to the perfusion parameters of the primary tumor (P > 0.05, respectively). Metastatic lymph node volume had a significant increasing effect on perfusion heterogeneity (P < 0.05, respectively) and BV in the primary was a highly significant factor for BV in metastatic disease (P < 0.001). Conclusion: Perfusion characteristics of mediastinal metastatic and non-metastatic lymph nodes in untreated lung cancer show considerable overlap, so that a reliable differentiation via VPCT is not possible.
PMCID: PMC3719054  PMID: 23876521
Lung cancer; metastasis; volume perfusion CT; VPCT; Ktrans
2.  Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue sarcoma mimicking myeloproliferative neoplasia: a case report 
BMC Research Notes  2014;7:313.
While paraneoplastic leukocytosis is a common phenomenon in solid tumors, extreme elevations of white blood counts (WBC) in the range of more than 100,000/μl are uncommon in patients with non-hematologic malignancies. Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating factor (G-CSF) producing tumor is only seen on rare occasions.
Case presentation
Massive neutrophil leukocytosis of approximately 100,000/μl was diagnosed in a 57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma. A bone marrow trephine biopsy revealed massively increased granulopoiesis, but no evidence of monoclonal myeloproliferative disease. After the primary tumor had been resected, white blood count (WBC) plummeted and went back to nearly normal levels within one week. With progressive metastatic disease, granulocyte colony-stimulating factor (G-CSF) plasma levels were found to be increased by 10-fold. White blood count (WBC) strictly correlated with tumor burden and response to chemotherapy. In the final stage of treatment resistent disease, white blood count (WBC) approximated 300,000/μl.
We report on a granulocyte colony-stimulating factor (G-CSF) secreting undifferentiated endometrial sarcoma, which was associated with extreme neutrophil counts. White blood count (WBC) were closely correlated with tumor burden and associated with an aggressive clinical course. We suggest that paraneoplastic neutrophilia represents a poor prognostic sign in soft tissue sarcoma. In patients with similar constellations, antitumor therapy must not be delayed.
PMCID: PMC4039653  PMID: 24885681
Paraneoplastic leukocytosis; Neutrophilia; G-CSF; Sarcoma
3.  Volume and attenuation computed tomography measurements for interim evaluation of Hodgkin and follicular lymphoma as an additional surrogate parameter for more confident response monitoring: a pilot study 
Cancer Imaging  2011;11(1):155-162.
Purpose: To retrospectively determine the potential role of additional computed tomography (CT) attenuation measurements for interim response evaluation in residual masses of patients with Hodgkin disease (HD) and follicular non-Hodgkin lymphoma (NHL). Materials and methods: In this retrospective study, 39 patients with HD and 35 patients with NHL presented with residual masses at mid-treatment CT (after 2–4 cycles of chemotherapy) and were assessed via contrast-enhanced CT at baseline, mid-treatment and post-treatment. Volume was recorded as whole-tumour volume. A tumour attenuation ratio (TAR) was calculated as the quotient of attenuation between tumour and muscle at the respective point in time versus baseline. The standard deviation of attenuation values within the tumour volume was recorded to estimate tumour heterogeneity. Results were correlated with relapse-free survival determined at a minimum of 12 months after end-treatment CT. Results: Tumour volume and TAR at interim versus baseline control were significantly reduced in responders compared with non-responders, even after controlling for age, stage, treatment regimen, and baseline tumour volume. No significant differences with respect to the standard deviation of attenuation values within the tumour volumes (tumour heterogeneity) were observed. The volume and attenuation CT (VACT) criteria yielded the highest sensitivities and specificities for the identification of non-response at a threshold of a >20% increase in volume and an increase in TAR at interim control, i.e. 88% (NHL 80%, HD 100%) and 98% (NHL 97%, HD 100%), respectively. The negative predictive values reached by VACT analysis were ≥97%, according to both parameters. Conclusion: Mid-treatment response assessment of residual masses in patients with HD and NHL using VACT may aid in the risk stratification as an additional surrogate parameter.
PMCID: PMC3205764  PMID: 22042236
Hodgkin disease; follicular lymphoma; volume and attenuation CT; VACT; interim response evaluation
4.  Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma 
BMC Urology  2012;12:7.
Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma.
Case presentation
A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable.
Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.
PMCID: PMC3348004  PMID: 22436420
Paraneoplastic; Hypereosinophilia; Leukocytosis; Renal cell carcinoma; Leukemoid reaction; Encephalopathy
5.  Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity 
Korean Journal of Radiology  2010;11(5):547-552.
We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity.
Materials and Methods
An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs).
Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively.
Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans.
PMCID: PMC2930164  PMID: 20808699
Perfusion CT; Tumor vascularity; Radiation exposure; Effective dose; 128-slice CT; Alderson-Rando phantom
6.  Early MRI response monitoring of patients with advanced hepatocellular carcinoma under treatment with the multikinase inhibitor sorafenib 
BMC Cancer  2009;9:208.
New therapeutic principles in clinical oncology require the adjustment of response criteria to govern therapy decisions. For advanced hepatocellular carcinoma (HCC) a new era has recently begun by the approval of the multikinase inhibitor sorafenib. As a unique feature, HCC usually develops in a diseased liver and current imaging technologies employing classical response criteria have not been prospectively evaluated for this new treatment.
MRI signal patterns were assessed in 21 advanced HCC patients receiving sorafenib. MRI was performed at baseline and in short-term intervals thereafter. Signal changes under therapy on T1WI, T2WI and post-gadolinium images including necrosis volume and its ratio to the entire tumor volume were compared to baseline imaging. To assess the association between the categorical variables, Fisher's exact tests were applied for a statistical analysis. Survey time ranged from 2–65 weeks, and a total of 39 target lesions were evaluated.
Signal abnormalities during sorafenib therapy were disclosed by T1WI and T2WI in 15/21 patients. The predominant tumor signal change was hyperintensity on both T1WI and T2WI. Interestingly, most patients developed MRI signal changes within 4 weeks of therapy; in contrast, two non-responders did not show any signal alteration at follow-up. Under therapy, 16/21 patients presented with new or progressive necrosis, whereas 7 patients achieved temporarily >75% tumor necrosis under sorafenib. Significantly associated MRI variables were increase in T1WI signal and tumor necrosis (p = 0.017) as well as increase of tumor necrosis with an elevated ratio of necrotic to vital tumor areas (p = 0.002). Remarkably, some (3/13) of the patients developing necrotic tumor areas showed a relevant (>20%) increase in tumor volume, which should be considered in the assessment of imaging studies.
As sorafenib induces early intralesional necrosis with profound changes in T1WI/T2WI MRI signal intensities and measurable necrotic tumor areas in most HCC patients, early MRI-based evaluation could pave the way for its rationale and cost-effective application.
PMCID: PMC2714320  PMID: 19558720

Results 1-6 (6)