P4 radiology of hepatobiliary diseases with gadoxetic acid-enhanced MRI as a biomarker.

A recent paradigm shift in radiology has focused on the globalization of so-called P4 radiology. P4 radiology represents delivery of imaging results that are predictive, personalized, pre-emptive and participatory. The combination of the P4 approach and biomarkers is particularly pertinent to MRI, especially with technological advances such as diffusion-weighted imaging. The development of new liver-specific MRI contrast media, particularly gadoxetic acid, demonstrate specific pharmacokinetic properties, which provide combined morphologic and functional information in the same setting. The evaluation of hepatobiliary pathology beyond morphology gives rise to the possibilty of using gadoxetic acid-enhanced MRI as an imaging biomarker of hepatobiliary diseases. The integration of functional imaging with an understanding of complex disease mechanisms forms the basis for P4 radiology, which may ultimately lead to individualized, cost-effective, targeted therapy for patients. This will enable radiologists to determine the prognosis of the disease and estimate early response to treatment, with the participation of all the required medical disciplines.

Confident non-invasive diagnosis of pseudolesions of the liver using diffusion-weighted imaging at 3T MRI.

PURPOSE: Pseudolesions of the liver including focal steatosis or non-steatosis and THID (transient hepatic intensity differences) are often challenging, especially when imaging patients with underlying malignant disease. We evaluated the efficacy of diffusion-weighted imaging (DWI) in the diagnostic work-up of pseudolesions. MATERIALS AND METHODS: Forty-eight patients with pseudolesions of the liver were consecutively examined and the images were retrospectively analyzed. MRI was performed on a clinical 3T scanner using T1-GRE in-phase and opposed phase images, T2-TSE-FS, diffusion-weighted sequences (b-value 50, 300, 600), ADC mapping, and dynamic post-contrast T1-VIBE-FS sequences (32 patients received Gd-EB-DTPA and 16 patients received gadolinium chelates). All images were analyzed by two experienced radiologists in consensus. As a standard of reference, we used the T1-w GRE, in-phase and out of phase, and the contrast enhanced series, as well as long-term follow-up. RESULTS: In the 48 patients, a total of 116 liver lesions were found. Of these, 40 were benign and eleven were malignant focal lesions. Benign lesions included one FNH, 26 simple cysts, and twelve hemangiomas. In addition, 65 pseudolesions (20 focal steatosis, 13 focal non-steatosis, and 32 THIDs) were found. All pseudolesions could be identified either on the T1-GRE in-phase and opposed phase images or on the contrast-enhanced series, or on both. However, none of them were visible on the diffusion-weighted images. CONCLUSION: Pseudolesions are invisible on DWI (negative predictive value = 1); therefore, DWI can be used as an additional sequence to significantly increase diagnostic confidence in the differentiation between pseudolesions and other focal liver lesions.

Puumala virus infection: radiologic findings.

A 33-year-old male patient was admitted to our nephrology department with rapidly deteriorating general health, fever, respiratory difficulties, and acute renal failure. Computed tomography of the thorax revealed interstitial edema with thickening of the interlobular septa, peribronchial cuffing, ground-glass opacities, and small pleural and pericardial effusions. Polymerase chain reaction tests verified Puumala virus infection. The patient recovered with supportive treatment. Hantavirus infection should be considered in the differential diagnosis of young patients who present with acute renal failure of an unknown origin and the nonspecific radiologic finding of noncardiogenic interstitial edema, which in combination with typical clinical symptoms and laboratory parameters, can be indicative of this disease.

Intensified adjuvant IFADIC chemotherapy in combination with radiotherapy versus radiotherapy alone for soft tissue sarcoma: long-term follow-up of a prospective randomized feasibility trial.

Adjuvant chemotherapy for grade 2 and 3 soft tissue sarcoma (STS) patients still has to be considered experimental. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or in combination with six courses of chemotherapy consisting of ifosfamide, DTIC, and doxorubicin administered in 14-day intervals supported by G-CSF on days 5-13. Twenty-eight patients received radiotherapy (control group) and 31 patients were treated with additional chemotherapy. After a median observation period of 97 months (range: 13-158 months), 58 patients were followed up to assess long-term relapse-free survival (RFS), time to local failure (TLF), time to distant failure (TDF), and overall survival (OS). Fifteen patients (56%) in the control group vs. 19 patients (61%) in the chemotherapy group were free of disease. Within the control group, tumor relapses occurred in 12 patients (44%) vs. 12 patients (39%) in the chemotherapy group. RFS (P = 0.87), TLF (P = 0.58), TDF (P = 0.60) as well as OS (P = 0.99) did not differ significantly between the two groups. Adjuvant chemotherapy was not translated into a significant benefit concerning RFS, TLF, TDF, and OS for STS patients.

Automatic assessment of the knee alignment angle on full-limb radiographs.

In this study a fully automatic assessment of the knee alignment angles in full-limb radiographs was developed and compared to manual standard of reference measurements in a prospective manner. The data consisted of 28 knees which were gathered from total-leg radiographs of 15 patients (12 males and 3 females with a mean age of 29.4+/-6.9 years) consecutively. For statistical evaluation, a leave-one-out cross-validation was performed. The pattern recognition and consequently the fully automatic assessment were successful in all patients. The automatically measured angles highly correlated with the standard of reference (r=0.989). The mean absolute difference was 0.578 degrees (95% CI: 0.399-0.757 degrees ). 82% of the angles differed less than 1 degrees from the standard of reference, 46% differed less than 0.5 degrees and 31% differed less than 0.2 degrees . The automatic method showed a high agreement between repeated measurements (+0.515 degrees to -0.429 degrees ). The automatic assessment of alignment angles in full-limb radiographs were equal to the manual assessment. No measurement related user interaction was necessary to achieve results.

Magnetic resonance imaging of liver malignancies.

The histological structure of the liver is complex, consisting of hepatocytes, biliary epithelium, and mesenchymal cells. From this large variety of cells, a broad spectrum of benign and malignant liver lesions in originate. An accurate diagnosis of these lesions is mandatory for choosing an appropriate therapeutic approach. With the recent developments in hardware and software, magnetic resonance imaging (MRI) has emerged as the method of choice in the diagnostic workup of focal liver lesions, in particular in the pretherapeutic stage. The introduction of high-field MRI at 3.0 T in the routine workup and the selective use of liver-specific contrast agents, including hepatobiliary and reticuloendothelial agents, have also strengthened the role of MRI in liver imaging. In this overview article, we will review the recent developments in 3.0-T MRI and MRI contrast agents in the diagnostic workup of the most common malignant liver tumors.

Major response and clinical benefit following third-line treatment for Bellini duct carcinoma.

Bellini duct carcinoma accounts for 1-3% of all renal carcinomas and is characterized by an aggressive course and extremely poor prognosis. Conventional treatment for renal-cell carcinoma seems to be ineffective. Since the histology of Bellini duct carcinoma is similar to urothelial carcinoma, chemotherapy for urothelial cancer might be more promising than conventional treatment. We present a patient with renal carcinoma of the left kidney who underwent laparoscopic extrafascial nephrectomy and adrenalectomy. Histopathologic work-up showed Bellini duct carcinoma (pT3a, NX, G3, R0 and M0). Eight months after surgery, disease progression was observed with local recurrence, multiple pulmonal lesions, para-aortic and aortocaval lymphadenopathies and a solitary bone lesion. First-line treatment with interferon-alpha and interleukin-2, as well as second-line treatment with thalidomide, were ineffective. Disease progressed rapidly and the patient experienced a dramatic reduction in performance status and quality of life. Six courses of chemotherapy with cisplatin and gemcitabine were given, a treatment reported to be highly active in urothelial cancer. The treatment was well tolerated, with thrombopenia WHO grade II, anemia WHO grade I and nausea/vomitus WHO grade II being the most severe side effects. Follow-up computer tomography revealed partial remission with 50-100% response at the different sites of metastasis. This response was accompanied by a dramatic improvement in performance status (from an initial 60% to 100% Karnofsky index) and quality of life. The combination of cisplatin and gemcitabine was highly active in this patient with metastatic Bellini duct carcinoma, even given as third-line treatment. This regimen fulfils all criteria for palliative treatment, as our patient showed an impressive improvement in WHO performance status and therefore in quality of life. Histopathologic characteristics should be a major criterion for treatment strategy in renal carcinoma, particularly in Bellini duct carcinoma.

The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer is independent of p53 status.

PURPOSE: Her-2/neu and p53-mediated signalling have been shown to interact at various cellular levels. However, the clinical relevance of p53 alterations in patients receiving trastuzumab for Her-2/neu-overexpressing metastatic breast cancer (MBC) remains unknown. The present study was performed to corroborate previous in vitro findings from our laboratory showing that trastuzumab induces growth arrest and apoptosis in a p53-independent manner. METHOD: Retrospective immunohistochemical (IHC) analysis for p53 protein expression was carried out on tumour specimens from 104 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing MBC at a single institution. p53 status was correlated with response (R) and clinical benefit (CB), median progression-free survival (PFS) time and overall survival (OAS) time in univariate and multivariate analyses. RESULTS: Characteristics were similar between p53-negative and p53-positive tumours (all P>0.05). In univariate analyses, R (39% vs 26%, P=0.208), CB (70% vs 57%, P=0.218), PFS (6.2 months vs 4.2 months, P=0.186) and OAS (23.8 months vs 23.2 months, P=0.650) were similar for p53-positive tumours and p53-negative tumours, respectively. In multivariate analyses, p53 status was not a significant predictor of R, CB, PFS or OAS (all P>0.05). CONCLUSIONS: p53 status, as determined by IHC, is not a predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu-overexpressing MBC.

Glioblastoma with spinal seeding.

BACKGROUND: Extracranial seeding of glioblastoma multiforme (GBM) is very rare and its development depends on several factors. This case report describes two patients suffering from GBM with spinal seeding. In both cases, the anatomic localization of the primary tumor close to the cerebrospinal fluid (CSF) was the main factor for spinal seeding. CASE REPORTS: Two patients with GBM and spinal seeding are presented. After diagnosis of spinal seeding, both patients were highly symptomatic from their spinal lesions. Case 1 experienced severe pain requiring opiates, and case 2 had paresis of lower limbs as well as urinary retention/incontinence. Both patients were treated with spinal radiation therapy. Nevertheless, they died 3 months after diagnosis of spinal seeding. RESULTS: In both patients the diagnosis of spinal seeding was made at the time of cranial recurrence. Both tumors showed close contact to the CSF initially. Even though the patients underwent intensive treatment, it was not possible to keep them in a symptom-free state. CONCLUSION: Because of short survival periods, patients deserve optimal pain management and dedicated palliative care.

Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy.

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.

Psychometric- and quality-of-life assessment in long-term glioblastoma survivors.

BACKGROUND: Multimodal treatment of patients with glioblastoma multiforme (GBM) allows an increasing number of patients to survive beyond one year. On account of various neurological and psychophysiological impairments, however, these patients may not benefit in terms of quality of life (QOL). We evaluated the subjective QOL, clinical psychophysiological and cognitive functions in patients with GBM surviving 18 months after diagnosis. PATIENTS AND METHODS: Thirteen patients underwent psychophysiological and psychometric measurements for central-nervous activation, habituation of skin-conductance reaction, crystallized intelligence, verbal and psychovisual memory. QOL was assessed by the symptom check-list for somatization (SCS-Score). RESULTS: We found various impairments such as central-nervous deactivation (n = 9) or high activation (n = 3), psychovegetative overexcitement (n = 3) or attenuation (n = 1), reduced verbal (n = 5) and/or psychovisual (n = 5) memory and loss in attention (n = 7) or concentration (n = 5). Severe physical symptoms (grade 5) were fatigue, convulsion, headache, nausea and micturition difficulties. Eleven patients expressed high satisfaction with life in general, whereas only 4 were satisfied with their general state of health. All patients were independent and 8 patients returned to work. CONCLUSION: Despite various psychophysiological and cognitive impairments, subjective QOL appears mostly unaffected in this patient setting.