[Oncologic aspects in treatment of pathologic fractures]. / Onkologische Aspekte der Behandlung pathologischer Frakturen.

BACKGROUND: Pathological fractures are not only incisive events for tumor patients often with the need of surgical treatment but also often represent a relevant challenge in the overall concept of oncological treatment. OBJECTIVE: The aim of this article is to illustrate the necessity of a pre-interventional interdisciplinary consideration of disease-specific and patient-specific characteristics. MATERIAL AND METHODS: A literature search and evaluation of existing guidelines were carried out including the keywords "bone metastases" and "pathological fractures" with respect to the oncological and radiotherapeutic treatment. RESULTS: An essential classification of the surgical and other needs for treatment is carried out by the identification of the underlying disease and dissemination situation. For tumor-related pathological fractures a palliative treatment situation is present in most cases. Nevertheless, a possible oligometastasis and an increasing number of effective systemic treatment methods must be taken into consideration when planning the surgical treatment. In addition to the therapeutic emergency indications in spinal compression or symptomatic hypercalcemia, both additive radiotherapy and supplementary pharmaceutical osteoprotection have to be addressed in this context. Radiotherapy in particular represents an effective alternative option for symptom and tumor control. CONCLUSION: The work-up of the multifaceted oncological treatment concept represents an interdisciplinary challenge, which ideally defines the further treatment procedure, including fracture treatment, in an interdisciplinary tumor board within an overall oncological concept.

Association of proton density fat fraction in adipose tissue with imaging-based and anthropometric obesity markers in adults.

BACKGROUND/OBJECTIVES: The purpose of this study was to examine the relationship of the proton density fat fraction (PDFF), measured by magnetic resonance imaging (MRI), of supraclavicular and gluteal adipose tissue with subcutaneous and visceral adipose tissue (SAT and VAT) volumes, liver fat fraction and anthropometric obesity markers. The supraclavicular fossa was selected as a typical location where brown adipocytes may be present in humans and the gluteal region was selected as a typical location enclosing primarily white adipocytes. SUBJECTS/METHODS: In this cross-sectional study, 61 adults (44 women, median age 29.3 years, range 21-68 years) underwent an MRI examination of the neck and the abdomen/pelvis (3T, Ingenia, Philips Healthcare). PDFF maps of the supraclavicular and gluteal adipose tissue and the liver were generated. Volumes of SAT and VAT were calculated and supraclavicular and subcutaneous fat were segmented using custom-built post-processing algorithms. Body mass index (BMI), waist circumference and waist-to-height ratio were recorded. Statistical analysis was conducted using the Student's t-test and Pearson correlation analysis. RESULTS: Mean supraclavicular PDFF was 75.3±4.7% (range 65.4-83.8%) and mean gluteal PDFF was 89.7±2.9% (range 82.2-94%), resulting in a significant difference (P<0.0001). Supraclavicular PDFF was positively correlated with VAT (r=0.76, P<0.0001), SAT (r=0.73, P<0.0001), liver PDFF (r=0.42, P=0.0008) and all measured anthropometric obesity markers. Gluteal subcutaneous PDFF also correlated with VAT (r=0.59, P<0.0001), SAT (r=0.63, P<0.0001), liver PDFF (r=0.3, P=0.02) and anthropometric obesity markers. CONCLUSIONS: The positive correlations between adipose tissue PDFF and imaging, as well as anthropometric obesity markers suggest that adipose tissue PDFF may be useful as a biomarker for improving the characterization of the obese phenotype, for risk stratification and for selection of appropriate treatment strategies.

Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC).

The immunological checkpoints of programmed death 1 and its ligand (PD-L1) are currently in focus as novel therapeutic targets in renal cell carcinoma (RCC). The aim of this study was to evaluate the prognostic association of PD-L1 expression in clear cell (cc) RCC with clinical parameters, tumor aggressiveness and overall survival (OS). Patients who underwent renal surgery due to RCC between 1994 and 2003 were retrospectively evaluated. Tumor specimens were analyzed for PD-L1 expression by immunohistochemistry. One hundred and seventy-seven ccRCC patients were eligible for analysis, in which 140 (79.1 %) were negative and 37 (20.9 %) were positive for PD-L1 expression. PD-L1 positivity was associated with female gender (p = 0.001), lymph node metastasis (p = 0.004), distant metastasis (p = 0.002), higher AJCC stage (p = 0.004), as well as advanced disease (pT3/4 and/or N+ and/or M1) (p < 0.001). Kaplan-Meier analysis revealed a significantly diminished 5- and 10-year overall survival of 46.7 and 28.3 % for PD-L1(+) compared to PD-L1(-) tumors with 66 and 53.4 % (p = 0.005), respectively. Univariate analysis showed a significant negative association of OS with PD-L1 positivity [p = 0.005; HR: 2 (95 % CI 1.2-3.3)], even though PD-L1 positivity only tends to predict independently the OS using multivariate analyses [p = 0.066; HR: 1.6 (95 % CI 0.98-2.7)]. PD-L1 expression in ccRCC is associated with parameters of aggressiveness, as well as with poor OS, even though PD-L1 status was not identified as a significant independent prognostic parameter. However, further studies in larger cohorts are warranted.

[Visual diagnosis while performing transurethral resection of bladder tumors: power or myth?]. / Blickdiagnose bei der transurethralen Resektion von Harnblasentumoren : Macht oder Mythos?

INTRODUCTION: The gold standard for diagnosis and immediate therapy of bladder cancer is a transurethral resection (TURB) followed by histopathologic evaluation. The aim of this study was to assess the reliability of visual diagnosis by the operating urologist concerning dignity (malignant/benign) and staging compared to histopathologic evaluation. This is especially crucial since early mitomycin C instillation is based on the urologist's first impression. STUDY DESIGN AND METHODS: This prospective study included 311 cases of TURB from five German institutions. Surgeons were asked to estimate dignity of the neoplasm, tumor stage, and grade according to a standardized questionnaire. RESULTS: The subjective estimation/visual diagnosis of the operating urologist achieved a sensitivity with respect to identifying malignant tumors as such of 97%, while specificity was only 41%. Accordingly, the positive (PPV) and negative predictive values (NPV) were 76% and 88%, respectively. In general, muscle invasive cancer was predicted more often than confirmed by pathology (PPV 52%). However, whenever muscle invasive cancer was excluded by the urologist, this was confirmed by the pathologist in most the cases (NPV 95%). The educational degree did not influence the reliability and predictive value of visual diagnosis. CONCLUSION: This study shows that urologists cannot reliably distinguish benign from malignant lesions of bladder mucosa-regardless of their educational degree. A reliable diagnosis of a pathologist is definitely needed to plan final therapeutic steps.

[Utility of the serum CRP value for assessing the prognosis and therapeutic response of urological malignancies]. / Stellenwert des Serum-CRP-Wertes zur Einschätzung von Prognose und therapeutischem Ansprechen urologischer Malignome.

C-reactive protein (CRP) is an unspecific marker of systemic inflammation. It is known to be elevated in autoimmune disease, traumata and malignancies. Increased CRP levels have specifically been shown to be associated with disease progression and prognosis in various studies on renal cell carcinoma and transitional cell carcinoma. Although CRP, unlike PSA, is neither organ-specific nor tumour-specific, studies were able to show that increased CRP values are an independent prognostic marker for tumour-specific survival of patients with prostate cancer. In metastatic and castration-resistant prostate cancer elevated CRP levels have been approved as a useful marker to estimate the extent of disease and mortality. CRP measurements in serum are standardised worldwide and widely used in daily clinical routine. However, until CRP can be firmly established as a prognostic marker in daily routine, we need validation of its prognostic and predictive value with large and preferably prospective multicentre studies.

[Influence of obesity on urological malignancies]. / Der Einfluss von Adipositas auf urologische Tumorerkrankungen.

BACKGROUND: Overweight presents a growing problem in our society; therefore, there is an increasing interest to understand the influence of obesity on urological forms of cancer. AIM: In prostate cancer the development of a more aggressive phenotype seems to correlate with obesity. In renal cell cancer (RCC) obesity is both, a risk factor for occurrence -and is also associated with an improved tumour-specific survival in patients with organ-confined disease following kidney surgery as well as overall survival of patients with advanced disease receiving VEGF(R)-targeted treatment. In contrast, even though an association between body mass index (BMI) and bladder cancer has been described the role of obesity in bladder cancer remains largely unclear as published data are contradictory. RESULTS: An update on currently available data focusing on the relationship between obesity and genitourinary malignancies is given in this review; however, basic research which is necessary to define the biological and metabolic effects associated with obesity and which might affect the development and progression of urological cancers, is indicated.

Fibronectin 1 protein expression in clear cell renal cell carcinoma.

Fibronectin 1 (FN1) is a glycoprotein that is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defenses and metastasis. The aim of this study was to elucidate the FN1 protein expression in renal cell carcinoma (RCC) and to determine its potential prognostic relevance. A total of 270 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Biomarker expression was determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 153 patients with complete follow-up data and pathologically proven clear cell carcinoma of the kidney. The follow-up group had a mean follow-up period of 83.8 months (IQR 26.2-136.2 months). The calculated median 5-year overall and tumor-specific survival rate of all 153 evaluable patients was 66.6 and 71.0%, respectively. A higher disease-related mortality rate was observed among patients with cytoplasmic FN1 expression (41.3 vs. 24.7%, p=0.039, Fisher's exact test). No significant correlation was found between FN1 staining and patient characteristics such as age, gender, tumor differentiation and visceral metastasis. However, there was a trend for FN1 expression and correlation with tumor stage and lymph node metastasis (p=0.085 and p=0.203; respectively). The Kaplan-Meier analysis revealed significant differences in the 5-year tumor-specific survival for patients with and without cytoplasmic FN1 expression (64.8 vs. 77.7%; p=0.035, log-rank test). However, results of the multivariate Cox regression analysis showed that FN1 expression was not an independent marker of either overall or tumor-specific survival. In conclusion, FN1 protein expression in RCC is associated with a higher disease-related mortality rate, indicating a possible role in RCC progression. Therefore, our data on FN1 encourage further investigations to determine the role of FN1 in RCC.

Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1) CpG island methylation in renal cell carcinoma.

The tumour suppressor gene hypermethylated in cancer 1 (HIC1) is a transcriptional repressor, which functionally cooperates with p53. Loss of HIC1 function is associated with the development of various tumor entities. The aim of this study was to elucidate the relevance of CpG island (CGI) methylation of HIC1 in renal cell carcinoma (RCC). DNA methylation of HIC1 was analysed in a total of 98 tumor and 70 tumor adjacent normal specimens. After conducting bisulfite conversion, relative methylation levels were quantitated using pyrosequencing. Relative methylation values were compared for paired tumor and normal specimen and for correlation with clinico-pathologic and follow-up data of patients. Tumor-specific hypermethylation could not be detected for the subregion of the HIC1 - CGI analyzed in this study. Comparing the level of methylation in tumors to clinicopathological data solely, patients without lymph node metastases demonstrated a higher level of methylation compared to patients with lymph node metastases (p=0.030). Patients recurrence-free survival (p=0.0074) both in univariate as well as bivariate cox regression analysis. This study identifies HIC1 hypermethylation in tumors as an independent predictor of reduced recurrence-free survival, which fits into our current understanding of hypermethylated HIC1 being a marker for poor prognosis. Therefore, HIC1 - CGI methylation could be a candidate marker to improve individualized therapy and risk stratification.

[Incidence and long-term prognosis of papillary renal cancer. Results of a retrospective multicenter study]. / Inzidenz und Langzeitprognose des papillären Nierenzellkarzinoms. Ergebnisse einer retrospektiven Multicenterstudie.

OBJECTIVES: Papillary renal cell carcinoma (pRCC) represents the largest subgroup of non-clear-cell kidney cancer. In this retrospective multicenter study, we assessed tumor characteristics and long-term prognosis of patients with pRCC in comparison with conventional clear-cell cancer (ccRCC). METHODS: We evaluated 2,804 patients who had undergone renal surgery for pRCC or ccRCC between 1990 and 2006. The mean follow-up was 65 months. RESULTS: Both pRCC and ccRCC groups were comparable concerning age, tumor grade and the incidence of regional lymph node metastasis at diagnosis. The percentage of male patients was higher in pRCC than in ccRCC (76.0% vs. 63.6%), pRCC patients suffered less often from advanced tumors (22.3% vs. 38.1%), visceral metastasis at diagnosis (8.1% vs. 14.5%) and died less frequently due to RCC progression (16.3% vs. 29.6%). Applying multivariable analyses pRCC was found to be an independent predictor of a favorable clinical course for patients with organ-confined RCC. In contrast in advanced disease papillary histology was significantly associated with a poor prognosis and early tumour-related death. CONCLUSIONS: pRCC seem to be stratified into two different prognostic groups. Localized pRCC has a significantly better prognosis than ccRCC. In contrast, advanced pRCC is characterized by a worse clinical outcome. Whether these two different pRCC cohorts are consistent with the recently defined types 1 and 2 pRCC subtypes or are characterized by other typical genetic alterations, which would lead to a novel pRCC subclassification is currently under investigation within the German Renal Cancer Network.

[Overweight is an advantageous prognostic marker in patients with clear cell kidney cancer]. / Übergewicht ist ein günstiger Prognosefaktor für Patienten mit Nierenzellkarzinom.

OBJECTIVES: Obesity increases the risk of developing renal cell carcinoma (RCC). We assessed whether different body mass index (BMI) levels and the body surface area (BSA) at the time of surgery had an effect on aggressiveness and long-term prognosis of RCC. METHODS: The study included 1,595 RCC patients with complete information about their BMI who had undergone surgery for renal cell cancer at the University Hospitals in Hannover (MHH) and Marburg between 1990 and 2005. The mean follow-up was 5.0 years. RESULTS: A higher BMI and a higher than average BSA were significantly associated with younger age. A high BMI value was additionally related to a lower tumor grade, the clear cell histological subtype, and metastasis at the time of diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 76.9% (BMI>30) and 72.6% (BMI 25-30) as opposed to 63.5% for patients with a BMI below 25 (p<0.001). However, the positive correlation between a high BMI and tumor-specific survival could be confirmed in multivariable analyses for localized clear cell RCC only. CONCLUSION: We identified BMI as an independent prognostic marker of improved cancer-specific survival in patients with RCC, particularly with organ-confined clear cell cancer.

Toward individualized SAR models and in vivo validation.

The specific absorption rate (SAR) is a limiting constraint in sequence design for high-field MRI. SAR estimation is typically performed by numerical simulations using generic human body models. This entails an intrinsic uncertainty in present SAR prediction. This study first investigates the required detail of human body models in terms of spatial resolution and the number of soft tissue classes required, based on finite-differences time-domain simulations of a 3 T body coil. The numerical results indicate that a resolution of 5 mm is sufficient for local SAR estimation. Moreover, a differentiation between fatty tissues, water-rich tissues, and the lungs was found to be essential to represent eddy current paths inside the human body. This study then proposes a novel approach for generating individualized body models from whole-body water-fat-separated MR data and applies it to volunteers. The SAR hotspots consistently occurred in the arms due to proximity to the body coil as well as in narrow regions of the muscles. An initial in vivo validation of the simulated fields in comparison with measured B(1)-field maps showed good qualitative and quantitative agreement.

[Ewing's sarcoma of the kidneys with simultaneous seminoma]. / Ewing-Sarkom der Niere bei gleichzeitig vorliegendem Seminom.

Extraosseous Ewing's sarcoma (EOE) is rarely observed in the urinogenital tract, which results in only sporadic descriptions of primary EOE of the kidneys in the literature with cytologic analyses. A timely diagnosis and differentiated therapy of this aggressive disease are compromised by its infrequent appearance and scarce available data. With a simultaneously diagnosed seminoma our case report supports and extends further the data collected so far.

Whole-heart imaging using undersampled radial phase encoding (RPE) and iterative sensitivity encoding (SENSE) reconstruction.

Whole-heart isotropic nonangulated cardiac magnetic resonance (CMR) is becoming an important protocol in simplifying MRI, since it reduces the need of cumbersome planning of angulations. However the acquisition times of whole-heart MRI are prohibitive due to the large fields of view (FOVs) and the high spatial resolution required for depicting small structures and vessels. To address this problem, we propose a three-dimensional (3D) acquisition scheme that combines Cartesian sampling in the readout direction with an undersampled radial scheme in the phase-encoding plane. Different undersampling patterns were investigated in combination with an iterative sensitivity encoding (SENSE) reconstruction and a 32-channel cardiac coil. Noise amplification maps were calculated to compare the performance of the different patterns using iterative SENSE reconstruction. The radial phase-encoding (RPE) scheme was implemented on a clinical MR scanner and tested on phantoms and healthy volunteers. The proposed method exhibits better image quality even for high acceleration factors (up to 12) in comparison to Cartesian acquisitions.

Free-breathing whole-heart coronary MRA with 3D radial SSFP and self-navigated image reconstruction.

Respiratory motion is a major source of artifacts in cardiac magnetic resonance imaging (MRI). Free-breathing techniques with pencil-beam navigators efficiently suppress respiratory motion and minimize the need for patient cooperation. However, the correlation between the measured navigator position and the actual position of the heart may be adversely affected by hysteretic effects, navigator position, and temporal delays between the navigators and the image acquisition. In addition, irregular breathing patterns during navigator-gated scanning may result in low scan efficiency and prolonged scan time. The purpose of this study was to develop and implement a self-navigated, free-breathing, whole-heart 3D coronary MRI technique that would overcome these shortcomings and improve the ease-of-use of coronary MRI. A signal synchronous with respiration was extracted directly from the echoes acquired for imaging, and the motion information was used for retrospective, rigid-body, through-plane motion correction. The images obtained from the self-navigated reconstruction were compared with the results from conventional, prospective, pencil-beam navigator tracking. Image quality was improved in phantom studies using self-navigation, while equivalent results were obtained with both techniques in preliminary in vivo studies.

Fast isotropic volumetric coronary MR angiography using free-breathing 3D radial balanced FFE acquisition.

A shortcoming of current coronary MRA methods with thin-slab 3D acquisitions is the time-consuming examination necessitated by extensive scout scanning and precise slice planning. To improve ease of use and cover larger parts of the anatomy, it appears desirable to image the entire heart with high spatial resolution instead. For this purpose, an isotropic 3D-radial acquisition was employed in this study. This method allows undersampling of k-space in all three spatial dimensions, and its insensitivity to motion enables extended acquisitions per cardiac cycle. We present initial phantom and in vivo results obtained in volunteers that demonstrate large volume coverage with high isotropic spatial resolution. We were able to visualize all major parts of the coronary arteries retrospectively from the volume data set without compromising the image quality. The scan time ranged from 10 to 14 min during free breathing at a heart rate of 60 bpm, which is comparable to that of a thin-slab protocol comprising multiple scans for each coronary artery.

Projection reconstruction balanced fast field echo for interactive real-time cardiac imaging.

A balanced fast field echo (FFE) sequence (also referred to as true fast imaging with steady precession (true FISP)), based on projection reconstruction (PR) is evaluated in combination with real-time reconstruction and interactive scanning capabilities for cardiac function studies. Cardiac image sequences obtained with the balanced PR-FFE method are compared with images obtained with a spin-warp (2D Fourier transform (2DFT)) technique. In particular, the representation of motion artifacts in both techniques is investigated. Balanced PR-FFE provides a similar contrast to spin-warp-related techniques, but is less sensitive to motion artifacts. The use of angular undersampling within balanced PR-FFE is examined as a means to increase temporal resolution while causing only minor artifacts. Furthermore, a modification of the profile order allows the reconstruction of PR images at different spatial and temporal resolution levels from the same data. This study shows that balanced PR-FFE is a robust tool for cardiac function studies.

[Control of low Legionella concentrations in pool water]. / Erfassung niedriger Legionellen-Konzentrationen in Badebeckenwasser.

The Legionella proof is necessary in pool water according to DIN 19 643 in case of possible aerosol formation. In lab tests it was proven that the direct spatulation of 1 ml water offers high-grade proof with high correlation of the determined concentration to the actual germ content. With very small germ concentrations, however, preceding filtration of larger sample volumes is necessary. During the investigation of routine samples a Legionella proof was possible thereby in individual cases, whereas direct spatulation remained negative.

Reversed spiral MR imaging.

Reversed spiral imaging is discussed as an approach that provides strong intrinsic T *(2) contrast without the need for long repetition times. In comparison to the conventional forward spiral method, the T *(2) contrast achieved by reversing the spiral k-space trajectory is similar and differs only for very fast relaxing species. The flow and motion sensitivity of the reversed approach is the same if flow compensation is applied, except for a flow-dependent voxel shift and the sign of the artifact pattern. By simulations as well as phantom and in vivo experiments, it is shown that the image quality in reversed spiral imaging is comparable to that obtained with the forward spiral method.

Fatty acid-depleted albumin induces the formation of echovirus A particles.

Picornavirus infection requires virus uncoating, associated with the production of 135S "A" particles and 80S empty particles from 160S mature virions, to release the RNA genome into the cell cytoplasm. Normal albumin inhibits this process. We now show that when depleted of fatty acids, albumin induces the formation of echovirus A particles.