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Esophageal cancer: the role of integrated CT-PET in initial staging and response assessment after preoperative therapy.

Esophageal cancer, an uncommon neoplasm, has been increasing in incidence over the past few decades. Optimal management of patients is determined by the stage of disease at presentation, patient performance status, and location of the primary cancer. Recently, there has been increasing use of multimodality therapy in suitable candidates that employs preoperative chemotherapy and/or radiation followed by surgical resection. This evolving treatment strategy together with the substantial morbidity and mortality associated with esophagectomy makes appropriate patient selection critical. Computed tomography (CT) and endoscopy/endoscopic ultrasonography are usually carried out to initially stage patients with esophageal cancer, to determine primary tumor response, and to detect nodal and distant metastases after preoperative therapy. Positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose and integrated CT-PET are useful in the initial staging of patients with esophageal cancer and in the prediction of pathologic response, disease-free interval, and overall survival after preoperative therapy. Importantly, integrated CT-PET imaging decreases the number of futile attempts at surgical resection, mainly because of the detection of occult distant metastases. The following sections review the use of integrated CT-PET imaging in determining the T, N, and M descriptors of the American Joint Commission on Cancer's 2002 guidelines for pathologic and clinical staging at initial diagnosis and after chemoradiation therapy in those patients being considered for surgical resection.

Algorithms↗

[Rational of oncological surgery in multimodality treatment of cancers].

The infiltrative cancers permanently swarm circulating cancer cells, and in 2006 it is no more possible to consider that localized cancer exists. So, we must question our self about the place of a treatment like surgery, which is localized in the time and in the space. Moreover, it is now proved that surgery increases the number of circulating cancers cells, gives a transient immunodepression which promotes cancer implantations, and that the cicatrisation stimulates growth factors, which act also on tumor growth. In spite of these deleterious effects, the oncological surgery stays an important tool by achieving an optimal cytoreductive surgery which facilitates the effect of the adjuvant treatments, by eliminating the vascular sanctuaries present in the center of any big tumor, and because it is a striking-force very localized in the space and in the time. The role of the oncological surgery must be integrated in the new aspect of the biology of the tumors and must take in account the recent improvements concerning functional imaging, genomic and proteomic. It is currently only one of the different compounds of the multimodality treatments for cancers, and its modalities, as its timing must be reconsidered. At last, considering the future technologies, we must elaborate the future modalities of the oncological surgery.

Chemotherapy, Adjuvant↗

Iron-Deprivation Liposomes for Cancer Therapy.

Targeting iron homeostasis in tumor cells represents a promising anticancer strategy, as iron plays essential roles in tumor growth, invasion, and metastasis. Although deferoxamine can effectively chelate iron, its clinical application is limited by poor membrane permeability, short half-life, and lack of targeting capability. To overcome these challenges, we designed and synthesized a family of DFO-bearing lipids by modifying the molecule with dual fatty acid chains of varying lengths, and co-assembled them with auxiliary lipids via microfluidics to construct "iron-deprivation" liposomes. Among them, the medium-chain DFO-C12-liposomes exhibited the highest cellular uptake, iron-deprivation efficiency, and anticancer activity in vitro, markedly depleting mitochondrial iron, disrupting Fe-S cluster synthesis, suppressing mitochondrial respiration, and inducing autophagy. Furthermore, DFO-C12-liposomes efficiently coordinated Mn2 + via DFO-Mn2 + chelation, providing MRI capability while inducing iron deprivation-mediated ferroptosis. In addition, the iron-deprivation liposomes can encapsulate anticancer drugs such as doxorubicin, leading to an enhanced antitumor effect through the combination of iron deprivation and chemotherapy for osteosarcoma treatment. In summary, the "iron-deprivation" liposomes integrate iron chelation, imaging functionality, and chain-length-dependent cellular uptake into a versatile nanoplatform for regulating tumor iron homeostasis and achieving enhanced antitumor efficacy through multimodal therapeutic strategies.

alkyl chain‐length engineering↗

Esthesioneuroblastoma in childhood and adolescence. Better prognosis with multimodal treatment?

BACKGROUND AND PURPOSE: Only 3% of all malignant intranasal tumors are esthesioneuroblastomas (ENB) and only 20% of these rare neuroectodermal tumors are diagnosed up to 20 years of age. Radiotherapy and surgery are established treatment modalities for these patients, but the role of chemotherapy, especially in a multimodal approach, is not well defined. To investigate the influence of radio- and chemotherapy, the treatment and course of the disease in children and adolescents with ENB were analyzed retrospectively. PATIENTS AND METHODS: 19 unselected patients (nine male and ten female) diagnosed with ENB < or = 20 years of age were included in this analysis. Median age at diagnosis was 14.0 years (range, 5-20 years). The tumors were Kadish stage B in 4/19 patients and stage C in 15/19 patients. 17 patients underwent surgery, either without further therapy (n = 4), followed by radiotherapy (n = 1) or as part of multimodal regimens (n = 12). Two patients received radio- and chemotherapy without surgery. Complete resection (R0) was achieved in 15 out of 17 patients with surgery including all five patients with preoperative chemotherapy due to unresectable primary at diagnosis. RESULTS: The 5-year overall survival (OS) for the whole group was 73% +/- 12% and the 5-year event-free survival (EFS) 55% +/- 13%. None of the four patients with stage B experienced tumor progression so far, whereas seven out of 15 patients with stage C did (5-year EFS 47% +/- 14%; not significant). Patients with Kadish stage C and multimodal treatment strategies combing surgery, chemo- and radiotherapy had a significantly better outcome than patients with stage C and less than three treatment modalities (65% +/- 17% vs. 20% +/- 18%; p = 0.02). CONCLUSION: These data indicate a benefit of multimodal treatment regimens combining surgery, chemo- and radiotherapy for pediatric patients with ENB Kadish stage C. Chemotherapy appears to improve resectability, EFS, and OS. Radiotherapy is an integral part in the management of children and young adolescents with ENB in Kadish stage B and C.

Adolescent↗

[Termination of inpatient treatment for anorexia nervosa].

BACKGROUND: Dropout is a neglected area of research; patients with anorexia nervosa are a group with high risk for dropout. RESEARCH QUESTIONS: 1. What are the frequency and type of dropout in disorder-specific, integrated treatment programs for anorexic patients? 2. What are the predictors for dropout? METHOD: Analysis of 80 prospectively documented, consecutive treatment episodes of anorexic inpatients, based on multimodal clinical and psychometric parameters. RESULTS: Twenty percent of patients terminated on their own initiative, often after reaching target weight; 10% were discharged by the treatment team. At least 43% of dropouts continued with some sort of psychotherapy within the 3 months after discharge. Previous dropout was a predictor for dropout in the present episodes. Patients with no comorbidity had a higher risk of dropout. Patients discharged by the team had personality disorders more often. Patients with comorbid depression stayed in treatment. CONCLUSIONS: The form of termination of treatment should be routinely assessed. Previous dropout and comorbidity are indicators of the risk of dropout.

Adolescent↗

Neuroimaging advances and the transformation of acute stroke care.

Neuroimaging techniques have transformed the delivery of stroke care. Multimodal computed tomography and magnetic resonance imaging rapidly illustrate the vascular and parenchymal correlates in acute ischemic and hemorrhagic stroke. Optimal selection of thrombolytic candidates and the characterization of ischemic sequelae may be achieved with imaging. The nature and topography of intracerebral hemorrhage may also be defined. Increasing use of multimodal imaging in acute stroke has expanded our current understanding of stroke pathophysiology and streamlined the care of stroke patients from the hyperacute to chronic phases. The integration of neuroimaging techniques in research studies has elucidated pitfalls in the translation of novel therapy into clinical practice. This review explores the impact of neuroimaging advances in stroke and emphasizes the critical role of these modalities in the care of patients with ischemic and hemorrhagic events.

Brain Ischemia↗

Passive directional discrimination in laser-Doppler anemometry by the two-wavelength quadrature homodyne technique.

We report a method for passive optical directional discrimination in laser-Doppler anemometers. For this purpose frequency-shift elements such as acousto-optic modulators, which are bulky and difficult to align during assembly, have traditionally been employed. We propose to use a quadrature homodyne technique to achieve directional discrimination of the fluid flow without any frequency-shift elements. It is based on the employment of two laser wavelengths, which generate two interference fringe systems with a phase shift of a quarter of the common fringe spacing. Measurement signal pairs with a direction-dependent phase shift of +/- pi/2 are generated. As a robust signal-processing technique, the cross-correlation technique is used. The principles of quadrature homodyne laser-Doppler anemometry are investigated. A setup that provides a constant phase shift of pi/2 throughout the entire measurement volume was achieved with both single-mode and multimode radiation. The directional discrimination was successfully verified with wind tunnel measurements. The complete passive technique offers the potential of building miniaturized measurement heads that can be integrated, e.g., into wind tunnel models.

Journal Article↗

The integration of newer agents into neoadjuvant therapy.

The overall prognosis for N2 non-small cell lung cancer treated by surgical resection alone is dismal. At this stage, the disease is systemic, and the presence of occult micrometastases leads to relapse in the majority of cases. Progress against the disease therefore requires a multimodality approach involving chemotherapy, radiotherapy, and surgery. At least two randomized trials have demonstrated that cisplatin-based induction chemotherapy before surgery substantially improves median and 5-year survival compared with surgery alone. Induction chemotherapy has an equally impressive effect when it precedes definitive thoracic radiotherapy. In both settings, cisplatin-based combinations can achieve cure in certain stage IIIA patients. Attaining complete resection and downstaging N2 disease are useful surrogates for long-term survival. One focus for future research is the earlier stages of disease, in which induction chemotherapy also may have a role. Another challenge is to integrate new active agents, such as docetaxel, into the neoadjuvant setting, and trials of either a cisplatin or a carboplatin plus docetaxel regimen are under way. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse and, hence, those in greatest need of chemotherapy.

Carcinoma, Non-Small-Cell Lung↗

Intersensory experience and early perceptual development: the role of spatial contiguity in Bobwhite quail chicks' responsiveness to multimodal maternal cues.

In contrast to the large body of work on young infants' capacity to perceive temporally based intersensory relations, little research has been done on the role of spatial contiguity in the development of audio-visual integration. This study examined the effects of early postnatal sensory experience on an avian neonate's responsiveness to the spatial contiguity between maternal auditory and visual cues. Specifically, we assessed whether a bobwhite quail chick's ability to respond to the correspondence between the location of auditory and visual events is affected by its sensory-stimulation history. Results revealed that chicks denied species-typical auditory or visual experience in the period immediately following hatching showed altered patterns of responsiveness to maternal auditory and visual cues. In particular, chicks that received modified postnatal sensory experience demonstrated a higher tolerance for audio-visual spatial discrepancy than did control chicks. These results provide evidence of the important role of sensory experience in the emergence of intersensory integration during the perinatal period and highlight the role of spatial information in early perceptual responsiveness to maternal cues.

Aging↗

Light enhances hydrodynamic signaling in the multimodal caudal photoreceptor interneurons of the crayfish.

1. The caudal photoreceptor (CPR) interneurons in the sixth abdominal ganglion of the crayfish are complex, multi-modal interneurons. These cells respond directly to light with tonic spike discharges, and they integrate synaptic input from an array of fili-form mechanoreceptors on the tailfan. They also provide input to rostral command centers, inducing backward walking at high firing frequencies, and thus directly influence behavior. 2. We recorded CPR activity in response to weak hydrodynamic stimulation of the tailfan mechanoreceptors while under varying intensities of light shined on the sixth ganglion. Spike trains were characterized according to the mean discharge rate (MDR) and the power spectrum from which the signal-to-noise ratio (SNR) was calculated. 3. Illumination of the CPR enhances the efficiency of transmitting mechanosensory signals. It does so by increasing the SNR of mechanosensory input received from tailfan receptors. A sevenfold, nonlinear increase in the SNRs was observed with increasing light intensity, an effect especially pronounced for weak hydrodynamic stimuli. In comparison with the dark, illumination of the ganglion lowered the hydrodynamic threshold and heightened the response to suprathreshold stimulation. Unlike the SNR, the MDR is little affected by mechanosensory input. 4. These results are compared with simulated electronic activity from an analogue threshold model and are discussed with respect to the mechanism of stochastic resonance.

Animals↗

Multimodal fetal transesophageal echocardiography for fetal cardiac intervention in sheep.

BACKGROUND: The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. METHODS AND RESULTS: We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.

Animals↗

Crossmodal integration for perception and action.

The integration of information from different sensory modalities has many advantages for human observers, including increase of salience, resolution of perceptual ambiguities, and unified perception of objects and surroundings. Several behavioral, electrophysiological and neuroimaging data collected in various tasks, including localization and detection of spatial events, crossmodal perception of object properties and scene analysis are reviewed here. All the results highlight the multiple faces of crossmodal interactions and provide converging evidence that the brain takes advantages of spatial and temporal coincidence between spatial events in the crossmodal binding of spatial features gathered through different modalities. Furthermore, the elaboration of a multimodal percept appears to be based on an adaptive combination of the contribution of each modality, according to the intrinsic reliability of sensory cue, which itself depends on the task at hand and the kind of perceptual cues involved in sensory processing. Computational models based on bayesian sensory estimation provide valuable explanations of the way perceptual system could perform such crossmodal integration. Recent anatomical evidence suggest that crossmodal interactions affect early stages of sensory processing, and could be mediated through a dynamic recurrent network involving backprojections from multimodal areas as well as lateral connections that can modulate the activity of primary sensory cortices, though future behavioral and neurophysiological studies should allow a better understanding of the underlying mechanisms.

Animals↗

Three- to five-dimensional biomedical multisensor imaging for the assessment of neurological (dys) function.

This report describes techniques and protocols implemented at the Geneva Canton University Hospitals (HUG) for the combination of various biomedical imaging modalities and sensors including electromagnetic tomography, to study, assess, and localize neurological (dys) function. The interest for this combination stems from the broad variety of information brought out by (functional) magnetic resonance imaging, magnetic resonance spectroscopy, computed tomography, single-photon emission tomography, positron emission tomography, and electromagnetic tomography. Combining these data allows morphology, metabolism, and function to be studied simultaneously, the complementary nature of the information from these modalities becoming evident when studying pathologies reflected by metabolic or electrophysiologic dysfunctions. Compared with other current multimodality approaches, the one at the HUG is totally compatible with both clinical and research protocols, and efficiently addresses the multidimensional registration and visualization issues. It also smoothly integrates electrophysiology and related data as fully featured modalities.

Computer Graphics↗

Meaningful survival in lung cancer patients.

Lung cancer is diagnosed at an advanced stage in a majority of patients. Recent advances made in the treatment of lung cancer have resulted in a prolongation in survival and an improvement in quality of life. The majority of lung cancer patients experience multiple symptoms, which result from both the cancer and its treatment. Fatigue and anemia cause significant morbidity and impaired quality of life among patients with lung cancer. They also contribute to a suboptimal response to treatment modalities such as radiation, decreased performance status, and poor patient compliance with treatment. The impact of anemia is frequently under-recognized. Improvements in survival made with multimodality therapy can only be meaningful when combined with interventions to improve symptoms and overall quality of life. Prompt recognition of these problems and early intervention are an integral part of cancer therapy. In this review, we discuss the impact of anemia and the treatment options that could contribute to a truly meaningful survival in lung cancer patients.

Anemia↗

Digital imaging, image processing, and three-dimensional computer graphics for radiology.

The acquisition of medical images and their display, manipulation, and applications have advanced significantly in the recent past. MR imaging using ultrafast echo planar and fast gradient-echo techniques have expanded application in cardiovascular studies, as well as in the brain and spinal cord. Spiral CT has the potential to revolutionize a well-established modality, subject to several important limitations. The postprocessing of medical sectional images from MR imaging, CT, ultrasound, positron emission tomography, and single-photon emission CT has rapidly grown in importance. We have seen the emergence of renewed and expanded applications of these images, suitably processed, in directing planning and performance of therapeutic procedures on patients through stereotactic techniques, intravascular ultrasound, robot surgery, and integrated displays. This more central role of three-dimensional imaging to medical care is new and will continue to grow. Research applications have recently appeared in neuromorphometry, multimodality registration, functional neuroimaging, quantitative coronary angiography, and saturation MR techniques for myocardial tissue tagging.

Computer Graphics↗

Surgical wound care: current views on minimising dressing-related pain.

Managing surgical wounds healing by primary intention is likely to become less problematic with the development of more effective advanced wound dressings; increasingly effective methods of medicated pain management; education; and advances in minimal access surgical (MAS) techniques. Future research is likely to focus on management of patients with surgical wounds healing by secondary intention. If so, management of surgical wound pain must become an integral part of assessment. Theatre practitioners, clinical nurses and surgical practitioners, working as part of the multidisciplinary team, are ideally placed to undertake this work and to include multimodal, holistic approaches to caring for surgical wounds and controlling surgical wound pain (Gould, 1999). Patient support and education is likely to become an increasing priority, particularly in view of the significant move from inpatient care to short-stay and day-case surgery.

Bandages↗

The episodic buffer: a new component of working memory?

In 1974, Baddeley and Hitch proposed a three-component model of working memory. Over the years, this has been successful in giving an integrated account not only of data from normal adults, but also neuropsychological, developmental and neuroimaging data. There are, however, a number of phenomena that are not readily captured by the original model. These are outlined here and a fourth component to the model, the episodic buffer, is proposed. It comprises a limited capacity system that provides temporary storage of information held in a multimodal code, which is capable of binding information from the subsidiary systems, and from long-term memory, into a unitary episodic representation. Conscious awareness is assumed to be the principal mode of retrieval from the buffer. The revised model differs from the old principally in focussing attention on the processes of integrating information, rather than on the isolation of the subsystems. In doing so, it provides a better basis for tackling the more complex aspects of executive control in working memory.

Journal Article↗

The function of phenomenal states: supramodular interaction theory.

Discovering the function of phenomenal states remains a formidable scientific challenge. Research on consciously penetrable conflicts (e.g., "pain-for-gain" scenarios) and impenetrable conflicts (as in the pupillary reflex, ventriloquism, and the McGurk effect [H. McGurk & J. MacDonald, 1976]) reveals that these states integrate diverse kinds of information to yield adaptive action. Supramodular interaction theory proposes that phenomenal states play an essential role in permitting interactions among supramodular response systems--agentic, independent, multimodal, information-processing structures defined by their concerns (e.g., instrumental action vs. certain bodily needs). Unlike unconscious processes (e.g., pupillary reflex), these processes may conflict with skeletal muscle plans, as described by the principle of parallel responses into skeletal muscle (PRISM). Without phenomenal states, these systems would be encapsulated and incapable of collectively influencing skeletomotor action.

Awareness↗