Peter Dankerl

A Retrieval-Based Computer-Aided Diagnosis System for the Characterization of Liver Lesions in CT Scans

RATIONALE AND OBJECTIVES To evaluate a computer-aided diagnosis (CADx) system for the characterization of liver lesions in computed tomography (CT) scans. The stand-alone predictive performance of the CADx system was assessed and compared to that of three radiologists who were provided with the same amount of image information to which the CADx system had access. MATERIALS AND METHODS The CADx system operates as an image search engine exploiting texture analysis of liver lesion image data for the lesion in question and lesions from a database. A region of interest drawn around an indeterminate liver lesion is used as input query. The CADx system retrieves lesions of similar histology (benign/malignant), density (hypodense/hyperdense), or type (cyst/hemangioma/metastasis). The systems performance was evaluated with leave-one-patient-out receiver operating characteristic area under the curve on 685 CT scans from 372 patients that contained 2325 liver lesions (193 <1 cm(3)). Sensitivity, specificity, and positive and negative predictive values were evaluated separately for subcentimeter lesions. Results were compared to those of three radiologists who rated 83 liver lesions (20 hemangiomas, 20 metastases, 20 cysts, 20 hepatocellular carcinomas, and 3 focal nodular hyperplasias) displaying only the liver. RESULTS The CADx systems leave-one-patient-out receiver operating characteristic area under the curve was 97.1% for density, 91.4% for histology, and 95.5% for lesion type. For subcentimeter lesions, input of additional semantic information improved the systems performance. The CADx system has been proved to significantly outperform radiologists in discriminating lesion histology and type, provided the radiologists have no access to information other than the image. The radiologists were most reliable in diagnosing hemangioma given the limited image data. CONCLUSIONS The CADx system under study discriminated reliably between various liver lesions, even outperforming radiologists when accessing the same image information and demonstrated promising performance in classifying subcentimeter lesions in particular.

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

BACKGROUND Reports on long-term (≥10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup. METHODS Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides were injected intradermally in high doses over 2 years. We performed serial immunomonitoring in all 53 evaluable patients. RESULTS Vaccine-specific immune responses including high-affinity, IFNγ-producing CD4+ and lytic polyfunctional CD8+ T cells were de novo induced or boosted in most patients. Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not further enhance such immune responses, while keyhole limpet hemocyanin (KLH) pulsing to provide unspecific CD4+ help promoted CD8+ T cell responses - notably, their longevity. An unexpected 19% of nonresectable metastatic melanoma patients are still alive after 11 years, a survival rate similar to that observed in ipilimumab-treated patients and achieved without any major (>grade 2) toxicity. Survival correlated significantly with the development of intense vaccine injection site reactions, and with blood eosinophilia after the first series of vaccinations, suggesting that prolonged survival was a consequence of DC vaccination. CONCLUSIONS Long-term survival in advanced melanoma patients undergoing DC vaccination is similar to ipilimumab-treated patients and occurs upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine injection site reactions occurring after the initial vaccinations. TRIAL REGISTRATION ClinicalTrials.gov NCT00053391. FUNDING European Community, Sixth Framework Programme (Cancerimmunotherapy LSHC-CT-2006-518234; DC-THERA LSHB-CT-2004-512074), and German Research Foundation (CRC 643, C1, Z2).

Effects on posture by different neuromuscular afferent stimulations and proprioceptive insoles: Rasterstereographic evaluation

Background: Proprioceptive neuromuscular stimulating insoles are increasingly applied in treating functional complaints, chronic pain, foot disorders and so on. Objectives: To evaluate rasterstereography as a tool in objectifying postural changes resulting from neuromuscular afferent stimulation and proprioceptive neuromuscular stimulating insoles and to compare the respective effects on posture. Study design: This is a prospective experimental study. Methods: A total of 27 healthy volunteers were consecutively exposed to six different varying intense neuromuscular afferent stimulating test conditions at three different times. One test condition featured proprioceptive neuromuscular stimulating insoles. In each test condition, a sequence of 12 rasterstereographic recordings of back shape was documented. Changes between six different test conditions and over time for 14 posture characterising parameters were investigated, for example, trunk inclination, pelvic torsion, lateral deviation of the spine’s amplitude or sagittal spinal curve. Results: Standard deviation of our rasterstereographic measurements (±2.67 mm) was better than in most comparable reference values. Different neuromuscular stimuli were found to provoke significant changes to various posture parameters, including trunk inclination, pelvic torsion and so on ( each p < 0.001, F-tests). Proprioceptive neuromuscular stimulating insoles induced significant changes for parameter lateral deviation of the spine’s amplitude (p = 0.03). Conclusion: Neuromuscular afferent stimulation and proprioceptive neuromuscular stimulating insoles induce postural changes, which can be detected reliably by rasterstereography. Clinical relevance We demonstrated that rasterstereography – a radiation-free imaging modality – enables visualisation and documentation of subtle postural changes induced by varying intense neuromuscular afferent stimulation and the application of proprioceptive neuromuscular stimulating insoles.

Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy

Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in neoadjuvant chemotherapy setting.

Evaluation of Rib Fractures on a Single-in-plane Image Reformation of the Rib Cage in CT Examinations

RATIONALE AND OBJECTIVES This study aimed to evaluate the diagnostic performance of using a reformatted single-in-plane image reformation of the rib cage for the detection of rib fractures in computed tomography (CT) examinations, employing different levels of radiological experience. MATERIALS AND METHODS We retrospectively evaluated 10 consecutive patients with and 10 patients without rib fractures, whose CT scans were reformatted to a single-in-plane image reformation of the rib cage. Eight readers (two radiologists, two residents in radiology, and four interns) independently evaluated the images for the presence of rib fractures using a reformatted single-in-plane image and a multi-planar image reformation. The time limit was 30 seconds for each read. A consensus of two radiologist readings was considered as the reference standard. Diagnostic performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) was assessed and evaluated per rib and per location (anterior, lateral, posterior). To determine the time limit, we prospectively analyzed the average time it took radiologists to assess the rib cage, in a bone window setting, in 50 routine CT examinations. McNemar test was used to compare the diagnostic performances. RESULTS Single image reformation was successful in all 20 patients. The sensitivity, specificity, PPV, and NPV for the detection of rib fractures using the conventional multi-planar read were 77.5%, 99.2%, 89.9%, and 98.0% for radiologists; 46.3%, 99.7%, 92.5%, and 95.3% for residents; and 29.4%, 99.4%, 82.5%, and 93.9% for interns, respectively. Sensitivity, PPV, and NPV increased across all three groups of experience, using the reformatted single-in-plane image of the rib cage (radiologists: 85.0%, 98.6%, and 98.7%; residents: 80.0%, 92.8%, and 98.2%; interns: 66.9%, 89.9%, and 97.1%), whereas specificity did not change significantly (99.9%, 99.4%, and 99.3%). The diagnostic performance of the interns and residents was significantly better when evaluating the single-in-plane image reformations (P < .01). The diagnostic performance of the radiologists was better when evaluating the single-in-plane image reformations; however, there was no significant difference (statistical power: 0.32). CONCLUSIONS The diagnostic performance for the detection of rib fractures, using CT images that have been reformatted to a single-in-plane image, improves for readers from different educational levels when the evaluation time is restricted to 30 seconds or less.

Stiff Young Woman.

The stiff person syndrome (SPS) is a rare autoimmune neurological disorder, featuring progressive stiffness and rigidity of the axial muscles (Rakocevic G et al. Muscle Nerve 2012; 45: 623). In most cases SPS is an idiopathic disease with a suspected prevalence of approximately one per million (Ciccoto G et al. Neurol Clin. 2013; 31: 319). However, in 5–10% of cases it presents as paraneoplastic disease (Alexopoulos H et al. Eur J Clin Invest 2012; 40: 1018), mostly in patients with small-cell lung carcinoma, breast carcinoma and melanoma (Pittock SJ et al. Ann Neurol 2005; 58: 96). Autoantibodies against amphiphysin, and gephyrin muscles (Rakocevic G et al. Muscle Nerve 2012; 45: 623) are strongly associated with the secondary paraneoplastic form. While idiopathic stiff person syndrome usually develops over months and features typical GAD (glutamic acid decarboxylase) antibodies (Jung YJ et al. J Mov Disord. 2014; 7: 19), the paraneoplastic version features a subacute onset (Byrne TN et al. N Engl J Med. 2012; 367: 851). Clinical presentation ranges from stiffness and spasms in the thoracoabdominal spine and proximal legs, to a change in posture and gait, worsening chronic pain and even paralysis.