Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase.

BACKGROUND: Follow-up care in breast cancer is still an issue of debate. Diagnostic methods are more sensitive, and more effective therapeutic options are now available. The risk of recurrence is not only influenced by tumour stage but also by the different molecular subtypes. This study was performed to evaluate the use of whole-body imaging combined with tumour marker monitoring for the early detection of asymptomatic metastatic breast cancer (MBC). METHODS: This analysis was performed as part of a follow-up study evaluating 813 patients with a median follow-up of 63 months. After primary therapy, all patients underwent tumour marker monitoring for CEA, CA 15-3 and CA 125 at 6-week intervals within an intensified diagnostic aftercare algorithm. A reproducible previously defined increase was considered as a strong indicator of MBC. From 2007 to 2010, 44 patients with tumour marker increase underwent whole-body magnetic resonance imaging and/or an FDG-PET/CT scan. Histological clarification and/or imaging follow-up were done. RESULTS: Metastases were detected in 65.9% (29/44) of patients, 13.6% (6/44) had secondary malignancies besides breast cancer and 20.5% (9/44) had no detectable malignancy. Limited disease was found in 24.1% (7/29) of patients. Median progression-free survival of MBC was 9.2 months and median overall survival was 41.1 months. The 3- and 5-year survival rates were 64.2% and 40.0%, respectively. CONCLUSIONS: A reproducible tumour marker increase followed by whole-body imaging is highly effective for early detection. By consequence, patients might benefit from earlier detection and improved therapeutic options with a prolonged survival.

FDG-PET-CT and whole-body MRI for triage in patients planned for radioembolisation therapy.

PURPOSE: The purpose was to evaluate the potential of FDG-PET-CT and whole-body MRI (WB-MRI) as diagnostic triage methods for patients planned for radioembolisation of metastatic liver disease. MATERIALS AND METHODS: 135 patients with multifocal liver metastases were evaluated for potential palliative therapy with radioembolisation using 90-Yttrium microspheres. All patients were examined consecutively with FDG-PET-CT and WB-MRI for exclusion of relevant extra-hepatic tumor manifestations. All patients underwent 99mTc-albumine angiography followed by scintigraphy to exclude significant hepato-pulmonary shunting. RESULTS: Out of the 135 patients included into the pre-therapeutic diagnostic algorithm, 56% were eligible and received radioembolisation, while 44% could not be treated. In 91% the exclusion criteria was diagnosis of significant extra-hepatic metastatic disease. In 85% exclusion diagnosis was made concordantly by both FDG-PET-CT and WB-MRI, in 9% diagnosis was provided by PET-CT, in 6% by WB-MRI alone. Patient-based sensitivity for detection of extra-hepatic disease was 94% for PET-CT and 91% for WB-MRI. False-positive diagnosis of extrahepatic disease leading to exclusion for radioembolisation therapy was made in 2% of patients, in one patient by PET-CT and in one patient by WB-MRI alone. Overall, specificity for inclusion of radioembolisation therapy by combining both modalities was 99%. In 9% of patients angiographic diagnosis made radioembolisation impossible, in 7% solely the angiographic findings were decisive. CONCLUSION: Both FDG-PET-CT and WB-MRI are efficient diagnostic triage methods for patients planned for radioembolisation of liver metastases. Overall, FDG-PET-CT shows a trend to higher diagnostic accuracy compared to WB-MRI and may be used as imaging method of choice as a standalone examination. In combination, both modalities exhibited high sensitivity for the diagnosis of extra-hepatic tumor manifestations and result in high specificity.

Changes in normal liver and spleen volume after radioembolization with (90)Y-resin microspheres in metastatic breast cancer patients: findings and clinical significance.

PURPOSE: In clinical trials with yttrium-90-resin-microspheres for the management of colorectal cancer liver metastases, it was observed that radioembolization might result in splenomegaly and an increase in portal vein size. Subclinical hepatitis in normal liver tissue as well as the effects of radioembolization and prior chemotherapy are suspected to be responsible for this phenomenon. The purpose of this study was to quantify the changes in liver and spleen volume and portal vein diameter after radioembolization. METHODS: Twenty-seven patients with liver-dominant metastatic disease from breast cancer who had not responded to chemotherapy or had to abandon chemotherapy because of its toxic effects were evaluated. Changes in liver and spleen volume and portal vein diameter as well as liver tumor volume and diameter were quantified using computed tomography scans. RESULTS: Radioembolization was associated with a significant mean decrease in the whole liver volume of 10.2% (median 16.7%; P = 0.0024), mainly caused by a reduction in the right lobe volume (mean 16.0%; P < 0.0001). These changes were accompanied by a significant increase in the diameter of the main portal vein (mean 6.8%; P < 0.0001) as well as splenic volume (mean 50.4%; P < 0.0001). Liver-tumor volume and diameter decreased by a median of 24 and 39.7%. CONCLUSIONS: Radioembolization is an effective treatment for tumor size reduction in patients with breast cancer liver metastases. Treatment is associated with changes of hepatic parenchymal volume, splenic volume, and portal vein size that appear not to represent clinically important sequelae in this patient cohort.

[Whole-body MRI and FDG-PET/CT imaging diagnostics in oncology]. / Ganzkörper-MRT und FDG-PET/CT in der bildgebenden onkologischen Diagnostik.

The advent of whole-body MRI (WB-MRI) has introduced a systemic approach to oncologic imaging compared to established sequential, multi-modal diagnostic algorithms. Hardware innovations, such as whole-body scanners at 1.5 Tesla and also recently 3 Tesla, combined with acquisition acceleration techniques, have made WB-MRI clinically feasible. With this method dedicated assessment of individual organs with various soft tissue contrast, high spatial resolution and contrast media dynamics can be combined with whole-body anatomic coverage.PET/CT has established itself as a powerful modality in the staging of patients suffering from malignant tumors. In addition to the morphologic information provided by the CT component of this hybrid modality, the PET component contributes invaluable metabolic information, which greatly enhances accuracy in the assessment of lymphatic spread and viability of tumor tissue. Whole-body MR diffusion imaging is a novel and promising technique which may contribute to superior sensitivity in the detection of tumor manifestations. In the assessment of distant metastatic spread WB-MRI is highly sensitive and has advantages over PET/CT, especially in those tumors frequently spreading to the liver, bone or brain. WB-MRI is also very attractive as a radiation-free alternative for imaging of pediatric tumor patients in whom multiple follow-up examinations may be required.WB-MRI allows for precise assessment of the bone marrow and has been proven to be highly accurate for the staging of hematologic diseases, such as multiple myeloma. In this article recent developments and applications of WB-MRI in oncologic imaging are addressed and compared to the results of PET/CT.

[Quantification of immunohistochemical expression of somatostatin receptors in neuroendocrine tumors using 68Ga-DOTATATE PET/CT]. / Quantifizierung der Somatostatinrezeptorexpression neuroendokriner Tumoren mit der (68)Ga-DOTATATE-PET/CT.

PURPOSE: The immunohistochemical expression of somatostatin receptor (SSTR) subtype 2 was compared to quantitative (68)Ga-DOTATATE PET in neuroendocrine tumors (NET). MATERIAL AND METHODS: In 27 patients suffering from metastatic NET the expression of somatostatin receptors (SSTR, score 0-3) and the Ki-67 index were assessed. The immunohistochemical findings were compared with the (68)Ga-DOTATATE PET uptake in these tumors using the SUV(max) (standardized uptake value). Both values were compared with the Ki-67 proliferation index. RESULTS: The SUV(max) in NET without SSTR expression was significantly lower compared to those with SSTR expression (p <0.05), even though 3 out of 5 NETs with a score of 0 showed a high uptake of (68)Ga-DOTATATE. The SUV(max) correlated significantly (r=0.40, p <0.05) with the score of immunohistochemical SSTR expression (negative, score 0, moderate, score 1 and high, scores 2 and 3). The Ki-67 index correlated inversely with the SSTR expression score (r=-0.42, p <0.05), but not significantly with the SUV(max) (r=-0.33, p=0.11). CONCLUSION: (68)Ga-DOTATATE uptake was moderately correlated with the results of immunohistochemical SSTR analyses. However, SSTR negative NET may show high uptake of (68)Ga-DOTATATE.

Whole-body MRI at 1.5 T and 3 T compared with FDG-PET-CT for the detection of tumour recurrence in patients with colorectal cancer.

The purpose of this study was to assess the diagnostic accuracy of whole-body MRI (WB-MRI) at 1.5 T or 3 T compared with FDG-PET-CT in the follow-up of patients suffering from colorectal cancer. In a retrospective study, 24 patients with a history of colorectal cancer and suspected tumour recurrence underwent FDG-PET-CT and WB-MRI with the use of parallel imaging (PAT) for follow-up. High resolution coronal T1w-TSE and STIR sequences at four body levels, HASTE imaging of the lungs, contrast-enhanced T1w- and T2w-TSE sequences of the liver, brain, abdomen and pelvis were performed, using WB-MRI at either 1.5 T (n = 14) or 3 T (n = 10). Presence of local recurrent tumour, lymph node involvement and distant metastatic disease was confirmed using radiological follow-up within at least 5 months as a standard of reference. Seventy seven malignant foci in 17 of 24 patients (71%) were detected with both WB-MRI and PET-CT. Both investigations concordantly revealed two local recurrent tumours. PET-CT detected significantly more lymph node metastases (sensitivity 93%, n = 27/29) than WB-MRI (sensitivity 63%, n = 18/29). PET-CT and WB-MRI achieved a similar sensitivity for the detection of organ metastases with 80% and 78%, respectively (37/46 and 36/46). WB-MRI detected brain metastases in one patient. One false-positive local tumour recurrence was indicated by PET-CT. Overall diagnostic accuracy for PET-CT was 91% (sensitivity 86%, specificity 96%) and 83% for WB-MRI (sensitivity 72%, specificity 93%), respectively. Examination time for WB-MRI at 1.5 T and 3 T was 52 min and 43 min, respectively; examination time for PET-CT was 103 min. Initial results suggest that differences in accuracy for local and distant metastases detection using FDG-PET-CT and WB-MRI for integrated screening of tumour recurrence in colorectal cancer depend on the location of the malignant focus. Our results show that nodal disease is better detected using PET-CT, whereas organ disease is depicted equally well by both investigations.

Pulmonary radiological characteristics in patients with HIV infection at the time of highly active antiretroviral therapy (HAART).

OBJECTIVE: To report on radiological and epidemiological characteristics of pulmonary disease in patients with HIV infection in times of highly active antiretroviral therapy (HAART). METHODS: Clinical data of 130 HIV infected adults with acute pulmonary symptoms were compared with findings in chest radiography (n = 130) and computed tomography (CT, n = 42). Presence and distribution of consolidation, interstitial changes, pleural effusion, and adenopathy were evaluated. Results were compared to findings from sputum, bronchoalveolar lavage, transbronchial biopsy, or empirical therapy results. RESULTS: 48% of patients presented pathologic findings. Overall sensitivity for the detection of pulmonary involvement was 0.87 (chest radiography) vs. 0.97 (CT). Disease specific sensitivity was 0.33 compared to 0.70. Bacterial pneumonia (BP, n = 26, 20%) was the most frequent diagnosis, followed by pneumocystis jiroveci pneumonia (PJP, n = 17, 13%), mycobacterium avium complex (MAC, 6%), Kaposi's sarcoma and lymphoma (KS and NHL, each 4%), fungal pneumonia (2%), and tuberculosis (TBC, 1%). Focal pulmonary infiltration was predominantly present in BP (50%, n = 13). Reticular (35%; n = 6) and micronodular (35%; n = 6) infiltration were predominantly found in PJP. CONCLUSIONS: Despite HAART, lung involvement is still common. Only contrast-enhanced computed tomography shows an acceptable disease-specific sensitivity. In unclear cases, CT should be performed.

Robust parametric modeling approach based on domain knowledge for computer aided detection of vertebrae column metastases in MRI.

This study evaluates a robust parametric modeling approach for computer-aided detection (CAD) of vertebrae column metastases in whole-body MRI. Our method involves constructing a model based on geometric primitives from purely anatomical knowledge of organ shapes and rough variability limits. The basic intensity range of primary 'simple' objects in our models is derived from expert knowledge of image formation and appearance for certain tissue types. We formulated the classification problem as a multiple instance learning problem for which a novel algorithm is designed based on Fisher's linear discriminant analysis. Evaluation of metastases detection algorithm is done on a separate test set as well as on the training set via leave-one-patient-out approach.

Whole-body MR imaging of bone marrow.

In clinical routine, multimodality algorithms, including X-ray, computed tomography, scintigraphy and MRI, are used in case of suspected bone marrow malignancy. Skeletal scintigraphy is widely used to asses metastatic disease to the bone, CT is the technique of choice to assess criteria of osseous destruction and bone stability. MRI is the only imaging technique that allows direct visualization of bone marrow and its components with high spatial resolution. The combination of unenhanced T1-weighted-spin echo- and turbo-STIR-sequences have shown to be most useful for the detection of bone marrow abnormalities and are able to discriminate benign from malignant bone marrow changes. Originally, whole-body MRI bone marrow screening was performed in sequential scanning techniques of five body levels with time consuming coil rearrangement and repositioning of the patient. The introduction of a rolling platform mounted on top of a conventional MRI examination table facilitated whole-body MR imaging and, with the use of fast gradient echo, T1-weighted and STIR-imaging techniques, for the first time allowed whole-body imaging within less than one hour. With the development of parallel imaging techniques (PAT) in combination with global matrix coil concepts, acquisition time could be reduced substantially without compromises in spatial resolution, enabling the implementation of more complex and flexible examination protocols. Whole-body MRI represents a new alternative to the stepwise multimodality concept for the detection of metastatic disease, multiple myeloma and lymphoma of the bone with high diagnostic accuracy.

[Estimation of diffuse bone marrow infiltration of the spine in multiple myeloma: correlation of MRT with histological results]. / Beurteilbarkeit diffuser Knochenmarksinfiltrationen der Wirbelsäule bei multiplem Myelom: Korrelation von MRT-Befunden mit der Histologie.

PURPOSE: To determine the detection of diffuse bone marrow infiltration with MRI in comparison with histopathological findings. MATERIALS AND METHODS: MRI was performed on 45 patients with histologically proven multiple myeloma and on 30 healthy individuals. Three experienced radiologists read separately Tl-weighted SE sequences, STIR sequences and the combination of Tl-weighted SE and STIR sequences of the spine. Additionally, Tl-weighted SE sequences were obtained after gadolinium administration and the percentage increase in signal intensity was calculated. Bone marrow histology was used as gold standard for assessing the grade of infiltration. A dichotomous decision (infiltration yes/no) was made when assessing the MRI examinations. RESULTS: For the visual detection of diffuse infiltration, the best sensitivity was found with Tl-weighted SE sequences, achieving 71 % on average. The specificity was 89 %. The STIR sequences showed a sensitivity of 61 % and a specificity of 98 %, and the combination of Tl-weighted/STIR-sequences achieved a sensitivity of 65 % and a specificity of 94 %. In comparison with the histological findings, the sensitivity of the Tl-weighted sequences was 35 % for low-grade, 89 % for moderate and 100 % for high-grade infiltration. The application of contrast material with calculation of the percentage signal increase improved the detection by 7 %. CONCLUSION: The sensitivity of the visual detection of diffuse multiple myeloma with unenhanced MRI is limited for low-grade or moderate infiltration, whereas the sensitivity for high grade infiltration is reliable. The specificity is high and the diagnostic confidence improves after application of contrast material with calculation of the percentage increase in signal intensity.

[Whole-body MRI and PET/CT in tumor diagnosis]. / Ganzkörper-MRT und PET-CT in der Tumordiagnostik.

Tumor staging according to the TNM-system influences prognosis and therapeutical options of patients with a malignant disease. It is the challenge of diagnostic imaging to depict the exact localization of the primary tumor and to detect or rule out lymph node involvement or distant metastases. In doing so, the complete body anatomy should be covered with a modality that offers high sensitivity and specificity. As these requirements could not or only partially be achieved by previous ordinary procedures, the use of multiple different modalities became necessary. Last but not least, in consideration of the costs it would be preferable to replace this cascade of different modalities by a "whole body examination", preconditioned that the same accuracy is achieved.With PET/CT and whole-body MRI, two newly available promising methods for a systemic tumor staging have been developed. First experiences indicate PET/CT as a method of first choice. With the introduction of new whole-body MRI scanners using parallel imaging technique (iPAT) and free table movement, MRI plays a more and more important role in whole body tumor staging.

[Comparison of high resolution whole-body MRI using parallel imaging and PET-CT. First experiences with a 32-channel MRI system]. / Hochauflösendes Ganzkörpertumorstaging unter Verwendung paralleler Bildgebung im Vergleich zur PET-CT. Erste Erfahrungen auf einem 32-Kanal-MRT-System.

PURPOSE: To compare the accuracy in the detection and staging of various malignant tumors with high resolution whole-body MRI using parallel imaging with whole-body dual-modality PET-CT. PATIENTS AND METHODS: Preliminary results of an interim analysis from a prospective, blinded study are presented, in which 20 patients (mean age 59 years, range 27-77 years) with different oncological diseases underwent whole-body dual modality FDG-PET-CT screening for tumor search or staging in case of confirmed or suspected metastatic disease. All patients also underwent whole-body MRI imaging with the use of parallel imaging (iPAT). High-resolution coronal T1w- and STIR-sequences of 5 body levels with 512 x 512 matrix, axial fast T2w imaging of lung and abdomen (HASTE), contrast-enhanced dynamic and static T1w-sequences of liver, brain, abdomen, and pelvis were performed. Using a 32-channel whole-body MRI scanner (Magnetom Avanto, Siemens Medical Solutions) with a total field of view of 205 cm and free table movement, all patients could be covered from head to toe within one examination. With this technique, high spatial resolution and acceptable scanning times could be obtained. Two experienced radiologists read the MRI-scans, one radiologist and one nuclear scientist read PET-CT scans, each in consensus in a clinical setting. Delineation of the primary tumor (T-stage) or recurrent tumor, pathologic lymph node involvement, as well as degree and localization of metastatic disease, was assessed using PET-CT as standard of reference. RESULTS: Metastases from gastrointestinal tumor (25%) and breast cancer (25%), genitourinary tumor (15%) and malignant melanoma (15%) were detected. In 4/20 patients the primary tumor was identified, 2/20 patients showed recurrent tumor. Of 140 malignant lesions detected by PET-CT, 124 lesions were detected with MRI, resulting in a sensitivity of 89% at a specificity of 86%. In malignant lymph node detection, sensitivity of MRI was 83% and specificity 85%. CONCLUSION: Whole-body MRI is a promising technique in the detection of primary tumor and metastatic disease. Sensitivity in the assessment of lymph node metastases seems to be limited. With the use of parallel imaging (iPAT), dedicated high-resolution whole-body MRI is possible within acceptable scanning times.

Effect of oral Escherichia coli inoculation on performance of young turkeys.

A strain of Escherichia coli isolated from the yolk sac of stunted turkey poults was administered orally to day-old large white poults. Poults were inoculated with either 0.1 ml of sterile broth or 0.1 ml of a 10(-2) dilution of a 24-hr E. coli culture containing 3.4 x 10(8) viable bacteria per ml. Two levels of dietary protein (28 or 22%) were fed from 1 day to 3 weeks of age. Following E. coli inoculation of 3.4 x 10(5) viable bacteria at day one, body weight gain and feed consumption from 0 to 3 weeks of age were numerically increased 4.5 and 2.1%, respectively, and feed efficiency was significantly increased 2.4%. E. coli had a greater effect on performance of poults fed the 28% protein diet than on poults fed the 22% protein diet. Metabolism studies, conducted from 7 to 10 and from 17 to 20 days postinoculation, showed no significant changes in the measurements of nutrient utilization due to E. coli other than a 17% increase in nitrogen retention from 17 to 20 days by those poults fed the 28% protein diet.

Dietary protein and yolk sac inoculation with Escherichia coli in young turkeys.

An experiment was conducted to examine the effect of pathogenic Escherichia coli inoculated into the yolk sac of day-old turkeys. Escherichia coli was isolated from the yolk sac of stunted poults and inoculated directly into the yolk sac of day-old birds. Poults were administered either .1 ml of uninoculated sterile Todd-Hewitt broth or .1 ml of a 10(-3) or 10(-2) dilution of a 24-hr E. coli culture containing 3.4 X 10(8) viable bacteria/ml. In addition, poults were fed either 28 or 22% protein diets from 0 to 21 days of age to form a 3 X 2 factorial arrangement. Body weight gain and feed consumption were measured weekly, and dry matter and protein retention and nitrogen-corrected metabolizable energy were measured from 7 to 10 and 17 to 20 days postinoculation. Intestinal mucosal dipeptidase and maltase activities were determined at 21 days of age. Average mortality by 7 days of age was increased from 1 to 36% from the E. coli inoculation of the yolk sac. Escherichia coli significantly depressed body weight gain and feed consumption 27 and 30, 13 and 16, and 6 and 8%, respectively, during the first, second, and third weeks of the experiment but failed to affect feed efficiency. Feeding a 28% protein diet alleviated the depression in feed consumption and body weight gain to some extent compared with a substantial depression at 22% protein. Nitrogen content and gross energy of the excreta were increased by both dilutions of E. coli for the 7 to 10-day period; this was indicative of a malabsorption of nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Frequency of the retroaortic left renal vein in adults (author's transl)]. / Uber die Häufigkeit der linken retroaortären Nierenvene bei Erwachsenen

In 231 adults the frequency and the pattern of the retroaortic left renal vein were studied. We observed a retroaortic left renal vein in 9.09% ("renal collar" in 5.62%, single retroaortic left renal vein in 3.46%. According to our results and to the findings in the literature a retroaortic left renal vein can be expected in 13.67% ("renal collar" in 9.53%, single retroaortic left renal vein in 4.13%).

[Absence of the vena cava inferior during simultaneous absence of the left kidney in a human fetus]. / "Fehlen" einer unteren Hohlvene bei gleichzeitigem Fehlen der linken Niere bei einem menschlichen Foeten

Atypical pattern of inferior cava (human embryo, sex: male, age: 6 month) is described. The left kidney is absent. The pelvis of the right kidney send two ureters to bladder. Pars hepatica of normal V. cava inferior is missed. Blood transport is formed by a vessel lateral of left suprarenal gland. This vessel is penetrating through pars lumbalis of diaphragm to thorax, goes in analogy to V. hemiazygos later to V. hemiazygos accessoria and flows into the right atrium.

[A special form of double vena cava inferior]. / Uber eine besondere Form der doppelseitigen V. cava inferior

In 231 cases the frequency of double inferior Cava in postrenal part is determined at 0.5%. The importance of double inferior Cava is discussed. This variation is the most frequent of V. cava inferior. The genesis is by persistence of left sacro-cardinal-vein (supracardinal-vein) over the six embryonical week. The casus, here mentioned, has an anastomosis overmore. This anastomosis cross Aorta and A. mesenterica inferior ventral, combines both inferior Cavae and must be interpreted as a second inferior Anastomosis intersubcardinalis.