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PubMed1983

The COMSTAT algorithm for multimodal factor analysis: an improvement of Tucker's three-mode factor analysis method.

Three-mode factor analysis, as developed by Tucker in 1966, is a method for nonredundant representation of data arrays with three subscripts (e.g. observations classified according to persons by variables by conditions). Tucker , however, did not succeed in obtaining a least-squares solution for his model. We derive in this paper a necessary condition for a least-squares solution and construct an algorithm which improves any given initial solution in the least-squares sense. We show that this algorithm converges to a representation satisfying the necessary conditions for a least-squares solution. The method is in no way restricted to three dimensions, but can be applied to any multimodal data array.

Alpha Rhythm↗
PubMed1997

The roles of multimodality treatment and lymphadenectomy in the management of esophageal cancer.

PURPOSE: To review the current status of multimodality treatment and lymphadenectomy in the management of esophageal cancer. DATA SOURCES: Literature review. STUDY SELECTION: Multimodality treatment and lymphadenectomy in esophageal cancer. DATA EXTRACTION: Results in research papers published selected by literature search. RESULTS: Numerous studies have been carried out attempting to define the roles of various neoadjuvant or adjuvant regimens in the treatment of esophageal cancer. These included the use of radiotherapy or chemotherapy alone or in different combinations, with or without surgical resection. Randomized trials have failed to show significant improvement compared with surgical resection alone, although downstaging of disease and benefits on subgroups of patients could be demonstrated. Whether the extent of resection can influence outcome was tested by varying the surgical approach, and by increasing the extent of lymphadenectomy. Although indirect evidence exists suggesting more extensive resection may improve long term prognosis, definitive proof is lacking. CONCLUSIONS: More well organized randomized controlled trials are needed to further elucidate the roles of these approaches in the treatment of esophageal cancer.

Combined Modality Therapy↗
PubMed2002

Cortical source estimate of combined high resolution EEG and fMRI data related to voluntary movements.

OBJECTIVES: In this paper, we employed advanced methods for the modeling of human cortical activity related to voluntary right one-digit movements from combined high-resolution electroencepholography (EEG) and functional magnetic resonance imaging (fMRI). METHODS: Multimodal integration between EEG and fMRI data was performed by using realistic head models, a large number of scalp electrodes (128) and the estimation of current density strengths by linear inverse estimation. RESULTS: Increasing of spatial details of the estimated cortical density distributions has been detected by using the proposed integration method with respect to the estimation using EEG data alone. CONCLUSION: The proposed method of multimodal EEG-fMRI data is useful to increase spatial resolution of movement-related potentials and can also be applied to other kinds of event-related potentials.

Brain Mapping↗
PubMed2025

Fundamentals of FAIR biomedical data analyses in the cloud using custom pipelines.

As the biomedical data ecosystem increasingly embraces the findable, accessible, interoperable, and reusable (FAIR) data principles to publish multimodal datasets to the cloud, opportunities for cloud-based research continue to expand. Besides the potential for accelerated and diverse biomedical discovery that comes from a harmonized data ecosystem, the cloud also presents a shift away from the standard practice of duplicating data to computational clusters or local computers for analysis. However, despite these benefits, researcher migration to the cloud has lagged, in part due to insufficient educational resources to train biomedical scientists on cloud infrastructure. There exists a conceptual lack especially around the crafting of custom analytic pipelines that require software not pre-installed by cloud analysis platforms. We here present three fundamental concepts necessary for custom pipeline creation in the cloud. These overarching concepts are workflow and cloud provider agnostic, extending the utility of this education to serve as a foundation for any computational analysis running any dataset in any biomedical cloud platform. We illustrate these concepts using one of our own custom analyses, a study using the case-parent trio design to detect sex-specific genetic effects on orofacial cleft (OFC) risk, which we crafted in the biomedical cloud analysis platform CAVATICA.

Cloud Computing↗
PubMed2001

Vestibular projections in the human cortex.

There is considerable evidence from studies on cats and monkeys that several cortical areas such as area 2v at the tip of the intraparietal sulcus, area 3av in the sulcus centralis, the parietoinsular vestibular cortex adjacent to the posterior insula (PIVC) and area 7 in the inferior parietal lobule are involved in the processing of vestibular information. Microelectrode recordings from these areas have shown that: (1) most of these cortical neurons are connected trisynaptically to the labyrinthine endorgans and (2) they receive converging vestibular, visual and somatosensory inputs. These data suggest that a multimodal cortical system is involved in postural and gaze control. In humans, recent positron emission tomography (PET) scans and functional magnetic resonance imaging (fMRI) studies have largely confirmed these data. However, because of the limited temporal resolution of these two methods, the minimum time of arrival of labyrinthine inputs from the vestibular hair cells to these cortical areas has not yet been determined. In this study, we used the evoked potential method to attempt to answer this question. Due to its excellent temporal resolution, this method is ideal for the investigation of the tri- or polysynaptic nature of the vestibulocortical pathways. Eleven volunteer patients, who underwent a vestibular neurectomy due to intractable Meniere's disease (MD) or acoustic neurinoma resection, were included in this experiment. Patients were anesthetized and the vestibular nerve was electrically stimulated. The evoked potentials were recorded by 30 subcutaneous active electrodes located on the scalp. The brain electrical source imaging (BESA) program (version 2.0, 1995) was used to calculate dipole sources. The latency period for the activation of five distinct cortical zones, including the prefrontal and/or the frontal lobe, the ipsilateral temporoparietal cortex, the anterior portion of the supplementary motor area (SMA) and the contralateral parietal cortex, was 6 ms. The short latency period recorded for each of these areas indicates that several trisynaptic pathways, passing through the vestibular nuclei and the thalamic neurons, link the primary vestibular afferents to the cortex. We suggest that all these areas, including the prefrontal area, process egomotion information and may be involved in planning motor synergies to counteract loss of equilibrium.

Brain Mapping↗
PubMed2004

PET/CT image navigation and communication.

UNLABELLED: The advent of multimodality imaging scanners combining PET and CT has led to a new paradigm in image display and presentation that raises new challenges in workstation interpretation software, image navigation, and communication. The essence of multimodality imaging is the ability to overlay imaging information from different modalities in a visually compelling fashion. This is accomplished by combining functional and anatomic data into multidimensional views using color-encoding techniques that provide visual clues on the spatial distribution of image data. DISCUSSION: Combined PET/CT scanners provide spatially registered images from the two modalities acquired simultaneously in a single imaging session. Special reconstruction software and image display programs are required to rescale the native images from different spatial resolution into orthogonal or oblique reformatted planes in which data from PET images are color coded and superimposed on corresponding anatomic CT images. The color overlay technique allows the user to visually identify areas of high tracer activity and determine the underlying anatomic structure. Because of the multidimensional nature of the data, visualization requires interactive multidimensional navigation techniques that allow the viewer to move the visualization planes through three spatial directions and two additional dimensions. The fourth dimension is the continuum blend from PET to CT fusion, and the fifth is the dynamic range of the CT images that can be adjusted to display different tissue characteristics, such as bones, soft tissue, and lungs. Software tools currently available are often relatively complex, requiring the user to perform cumbersome maneuvers and time-consuming image manipulation to navigate through all dimensions and obtain adequate image settings and plane positioning for diagnostic interpretation of the image data. Moreover, the ability to convey these images to referring physicians is usually limited because of the lack of adequate viewing software. Distribution of results is usually performed instead through static "snapshots" of the fused images generated by the interpreting radiologist. The ability of the referring physician to navigate through the set of multimodality image data is thus limited. CONCLUSION: The wider adoption of multimodality PET/CT imaging techniques in routine clinical use will depend heavily on the development of more adequate image display and navigation tools that allow interpreting physicians to navigate easily and efficiently through multiple dimensions of data. Distribution of results to referring physicians and care providers also requires new tools for interactively reviewing the multimodality data, and current static images obtained from fused image data remain inadequate for proper visualization of the true content of images.

Algorithms↗
PubMed2006

Synovial cell sarcoma of the vulva: multimodality treatment incorporating preoperative external-beam radiation, hemivulvectomy, flap reconstruction, interstitial brachytherapy, and chemotherapy.

BACKGROUND: Vulvar synovial cell sarcomas are rare, with only four previously published cases in the literature. Traditionally, the primary management for these tumors has been surgery alone. CASE: We report a case of a large vulvar synovial cell sarcoma in a 50-year-old woman treated with comprehensive combined multimodality management, including preoperative intensity-modulated radiation therapy, radical hemivulvectomy, flap reconstruction, interstitial low-dose-rate brachytherapy boost, and adjuvant chemotherapy. CONCLUSION: Based on this case and the limited data in the literature, multimodality treatment of advanced soft tissue sarcoma of the vulva may optimize local control and minimize toxicity while preserving sexual function.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Determination of the attenuation map in emission tomography.

Reliable attenuation correction methods for quantitative emission CT (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomic structure. Two broad classes of methods have been used to calculate the attenuation map: transmission-less and transmission-based attenuation correction techniques. Whereas calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications, where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and uses different approaches to determine this map, including transmission scanning, segmented magnetic resonance images, or appropriately scaled CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acquired from different imagers suffers from the usual problems of working with multimodality images--namely, accurate co-registration from the different modalities and assignment of attenuation coefficients. A current trend in ECT is to use transmission scanning to reconstruct the attenuation map. Combined ECT/CT imaging is an interesting approach; however, it considerably complicates both the scanner design and the data acquisition and processing protocols. Moreover, the cost of such systems may be prohibitive for small nuclear medicine departments. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This is being investigated either using a statistical model of emission data or applying the consistency conditions that allow one to identify the operator of the problem and, thus, to reconstruct the attenuation map. This article presents the physical and methodologic basis of attenuation correction and summarizes recent developments in algorithms used to compute the attenuation map in ECT. Other potential applications are also discussed.

Algorithms↗
PubMed1997

Multimodality treatment of thymoma: a prospective study.

BACKGROUND: Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy. METHODS: Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients. RESULTS: The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049). CONCLUSIONS: Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.

Adult↗
PubMed2026

Multimodal Integration of Protein Interactomes With Genomic and Molecular Data Discovers Distinct Rheumatoid Arthritis Endotypes.

OBJECTIVE: Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease characterized by clinical and molecular heterogeneity, notably in the presence of anti-cyclic citrullinated peptide (CCP) antibodies. Patients with CCP+ RA exhibit more severe disease progression and distinct treatment responses compared to patients with CCP- RA. Although previous studies have investigated cellular and molecular differences between these subtypes, their genetic differences are understudied. METHODS: We leveraged the Rheumatoid Arthritis Comparative Effectiveness Research cohort, comprising 555 patients with CCP+/rheumatoid factor (RF)+ RA and 384 patients with CCP-/RF+ RA. Using a novel framework, we integrated a network-based genome-wide association study (GWAS) with multiomic data to uncover corresponding genetic and molecular differences. RESULTS: We uncovered a significant heritability difference between these disease groups. Network-based GWAS uncovered 14 putative gene modules, including many genes outside the HLA loci, that explained genetic differences between CCP+/RF+ and CCP-/RF+ RA. Heritability partitioning and multivariate expression analyses validated four modules, highlighting novel genetic loci underlying phenotypic differences. Module functional significance was established using multiple orthogonal cohorts, underscoring their biologic relevance. CONCLUSION: Our findings demonstrate the use of network-based approaches in revealing differential genetic risk factors underlying CCP+/RF+ and CCP-/RF+ RA. Disease-associated gene modules detected in synovial tissue were also observed in peripheral blood, indicating joint-specific molecular programs are reflected systemically. This cross-tissue concordance highlights the potential for blood-based assays to capture pathogenic mechanisms active in the joints, enabling practical patient stratification. Our findings highlight why patients with CCP+/RF+ and CCP-/RF+ RA exhibit distinct clinical courses and therapeutic responses, supporting precision-guided treatment strategy development in RA.

Humans↗
PubMed2005

Estimation of the cortical functional connectivity with the multimodal integration of high-resolution EEG and fMRI data by directed transfer function.

Nowadays, several types of brain imaging device are available to provide images of the functional activity of the cerebral cortex based on hemodynamic, metabolic, or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions communicate with each other. In this study, advanced methods for the estimation of cortical connectivity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multidipole source model, and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. We estimate functional cortical connectivity by computing the directed transfer function (DTF) on the estimated cortical current density waveforms in regions of interest (ROIs) on the modeled cortical mantle. The proposed method was able to unveil the direction of the information flow between the cortical regions of interest, as it is directional in nature. Furthermore, this method allows to detect changes in the time course of information flow between cortical regions in different frequency bands. The reliability of these techniques was further demonstrated by elaboration of high-resolution EEG and fMRI signals collected during visually triggered finger movements in four healthy subjects. Connectivity patterns estimated for this task reveal an involvement of right parietal and bilateral premotor and prefrontal cortical areas. This cortical region involvement resembles that revealed in previous studies where visually triggered finger movements were analyzed with the use of separate EEG or fMRI measurements.

Adult↗
PubMed2003

Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture.

BACKGROUND: The pathophysiology of cerebral ischemia is well studied in small-animal models, which offer reproducibility and control of confounding variables-factors essential to hypothesis-testing. This presentation first highlights insights into the ischemic penumbra enabled by a multimodal experimental approach; second, discusses gene expression in ischemia; and third, confronts the challenges of neuroprotectant therapy. SUMMARY OF REVIEW: The ischemic penumbra: Transient (2-hour) middle cerebral artery suture-occlusion in anesthetized rats gives rise to highly consistent neurological and histopathological sequelae. Autoradiographic local cerebral blood flow (LCBF) studies at 2 hours of occlusion define the penumbra as a region of intermediate CBF depression (20% to 40% of control) surrounding the densely ischemic core (5% to 20% of control) and constituting one half of the entire lesion. Local glucose metabolic rate in the acute penumbra is not reduced despite the critical CBF reduction, so that the penumbral metabolism/blood flow ratio is markedly elevated. In contrast, following 1 hour of recirculation, glucose metabolism throughout the previously ischemic hemisphere has become markedly depressed, and the metabolism/flow ratio has pseudonormalized. By correlating these data with histopathology using multimodal image analysis, the probability of infarction is shown to be highly determined by the degree of antecedent CBF reduction. These animal data agree strikingly with published results in patients with acute stroke studied by positron emission tomography. This remarkable correspondence belies the assertion that data from lower species may not be relevant to human stroke. Gene expression: Perfusion gradients also determine differential patterns of gene expression in ischemia. This can be demonstrated by correlating in situ hybridization autoradiographs for gene expression with autoradiographic LCBF data and histological infarct maps derived from replicate series. In other studies, DNA microarray technology is used to screen for thousands of expressed genes. In the 2-hour middle cerebral artery occlusion model with 3-hour recirculation, we have identified 28 known ischemia-hypoxia response genes that are upregulated and 6 that are downregulated, together with 35 upregulated and 41 downregulated genes newly connected with ischemia. These findings underscore the enormous complexity of ischemic biology and suggest possible novel mechanisms for future exploration. NEUROPROTECTION: A desirable neuroprotectant would, in theory, antagonize multiple injury mechanisms. We have explored 2 such therapies of particular promise. Mild brain hypothermia (32 degrees C target temperature, for 5 hours) is highly neuroprotective even when initiated at the onset of recirculation. Another highly protective agent is human albumin, administered in doses of 1.25 to 2.5 g/kg--a therapy that reduces infarct volume in this ischemia model by 60% to 65%, markedly diminishes brain swelling, and has a therapeutic window extending to 4 hours. CONCLUSION: The careful study of rodent ischemia models can yield valuable, clinically relevant insights into the pathophysiology of ischemic stroke.

Albumins↗
PubMed1994

The National Cancer Data Base report on breast cancer.

BACKGROUND: Previous National Cancer Data Base data have been used to examine time trends in stage of disease and treatment patterns for breast cancer. The most current (1990) data are described here. METHODS: Two calls for data have yielded a total of 143,051 breast cancer cases for 1985, 1988, and 1990 from hospital cancer registries across the United States. RESULTS: The percentage of in situ cancers increased between 1985 and 1988 but was essentially constant between 1988 and 1990. The use of breast-conserving partial mastectomy across the country increased between 1988 and 1990. Some interesting regional differences appeared in the use of multimodality treatment. CONCLUSIONS: These data suggest a plateau in the use of mammographic screening.

Adult↗
PubMed1998

Intraoperative three-dimensional ultrasonography: an approach to register brain shift using multidimensional image processing.

Neuronavigation uses the skull as a reference system for transfer of image-space data to physical space during brain surgery. This requires a stable spatial relation between the skull and intracranial structures. However, especially dura opening and preparation for lesion removal causes brain shift. This shift may mislead the surgeon unless preoperatively defined image-space data are corrected for shifting online intraoperatively. Since a real-time modality is required intraoperatively, we propose three-dimensional (3 D) ultrasonography for detection of brain shift. By coupling common ultrasound probes (3.5/6.5 MHz) to a magnetic digitizer receiver 2 D-ultrasound scans were obtained intraoperatively along with their spatial orientation. 3 D-ultrasonography was achieved by alignment of sequentially obtained 2 D-scans. For multimodal matching, preoperative MRI data was segmented for landmarks (cerebral ventricles, lesion) automatically. The 3 D-ultrasonography data set scanned intraoperatively was contoured and matched with the MRI data set. Intraoperative 3 D-ultrasonography revealed excellent delineation of landmarks in almost real time in six patients studied. Matching of MRI data and intraoperative 3 D-ultrasonography data was successful with good correspondence of landmarks. Intraoperative 3 D-ultrasonography is proposed as a promising tool for on-line detection of brain shift during intracranial operations.

Adult↗
PubMed2006

Searching for convergence in phylogenetic Markov chain Monte Carlo.

Markov chain Monte Carlo (MCMC) is a methodology that is gaining widespread use in the phylogenetics community and is central to phylogenetic software packages such as MrBayes. An important issue for users of MCMC methods is how to select appropriate values for adjustable parameters such as the length of the Markov chain or chains, the sampling density, the proposal mechanism, and, if Metropolis-coupled MCMC is being used, the number of heated chains and their temperatures. Although some parameter settings have been examined in detail in the literature, others are frequently chosen with more regard to computational time or personal experience with other data sets. Such choices may lead to inadequate sampling of tree space or an inefficient use of computational resources. We performed a detailed study of convergence and mixing for 70 randomly selected, putatively orthologous protein sets with different sizes and taxonomic compositions. Replicated runs from multiple random starting points permit a more rigorous assessment of convergence, and we developed two novel statistics, delta and epsilon, for this purpose. Although likelihood values invariably stabilized quickly, adequate sampling of the posterior distribution of tree topologies took considerably longer. Our results suggest that multimodality is common for data sets with 30 or more taxa and that this results in slow convergence and mixing. However, we also found that the pragmatic approach of combining data from several short, replicated runs into a "metachain" to estimate bipartition posterior probabilities provided good approximations, and that such estimates were no worse in approximating a reference posterior distribution than those obtained using a single long run of the same length as the metachain. Precision appears to be best when heated Markov chains have low temperatures, whereas chains with high temperatures appear to sample trees with high posterior probabilities only rarely.

Bayes Theorem↗
PubMed2006

Spinal cord monitoring in scoliosis surgery using an epidural electrode. Results of a prospective, consecutive series of 191 cases.

STUDY DESIGN: Retrospective analysis of a prospectively accrued series of 191 consecutive patients who underwent intraoperative neurophysiologic monitoring during scoliosis corrective surgery. OBJECTIVES: To compare the monitoring outcome of idiopathic and neuromuscular scoliosis. To demonstrate the usefulness of the epidural electrode. To report sensitivity and specificity of the monitoring method employed at a single institution. SUMMARY OF BACKGROUND DATA: Reports in the literature emphasized the difficulty to obtain data in neuromuscular patients. Multimodality spinal cord monitoring has been recommended. Despite their still debated composition, neurogenic motor-evoked potentials have proven their validity in clinical practice. METHODS: Somatosensory and neurogenic evoked potentials were attempted in all patients presenting for scoliosis correction between 1999 and 2005. Study patients were divided into 3 groups: group 1, idiopathic; group 2, neuromuscular; and group 3, miscellaneous origins. RESULTS: The use of the epidural electrode demonstrated significant usefulness in the ability of monitoring otherwise nonmonitored patients, especially in group 2. Inability to obtain any evoked potentials occurred in 4 cases (2.1%). Five cases were found to be true positives. An adapted and rapid intervention permitted to avoid new postoperative deficit in all cases. There was no instance of false-negative data. The overall method sensitivity was 100%, and specificity was 52.69%. CONCLUSIONS: The use of a single epidural electrode allowing somatosensory evoked potentials recording and spinal cord stimulation alternately is a safe and valid method of intraoperative monitoring.

Adolescent↗
PubMed1991

Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma.

Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Multimodal genetic diagnosis of solid variant alveolar rhabdomyosarcoma.

The most common types of rhabdomyosarcoma (RMS) are alveolar RMS (ARMS), which are characterized by the specific translocation t(2;13)(q35;q14) or its rarer variant, t(1;13)(p36;q14), producing the fusion genes PAX3-FKHR and PAX7-FKHR, respectively, and embryonal RMS (ERMS), which is characterized by multiple numeric chromosome changes. A solid variant of ARMS that is morphologically indistinguishable from ERMS has been described recently. We present two cases with an initial histopathologic diagnosis of ERMS in which the combined findings by cytogenetic, reverse-transcriptase polymerase chain reaction (RT-PCR), and comparative genomic hybridization (CGH) analyses demonstrate that both tumors were in fact the solid variant of ARMS. The cytogenetic analysis of patient 1 revealed a t(2;13)(q35;q14) and the RT-PCR study detected the corresponding PAX3-FKHR chimeric transcript. In patient 2, the cytogenetic finding of multiple trisomies was compatible with the initial histopathologic diagnosis of ERMS, but the finding of a PAX7-FKHR fusion transcript by RT-PCR pointed to the diagnosis of ARMS. Interestingly, the CGH findings of this case reconciled the molecular and cytogenetic data by detecting, in addition to the trisomies, amplification of chromosomal bands 1p36 and 13q14, where the PAX7 and FKHR genes are located, respectively. Our data indicate that this multimodal genetic analysis could be important for the differential diagnosis of these tumors. Furthermore, our findings and previous studies indicate that there are no apparent genetic differences between solid variant and typical ARMS.

Base Sequence↗