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PubMed1979

Multimodal primary cancer treatment (adjuvant chemotherapy): current results and future prospects.

In the 1970s chemotherapy has been successfully incorporated into curative primary treatment programs for various adult malignancies so that it is no longer solely palliative treatment for advanced disease. For at least three malignancies and tentatively a fourth (breast and colon carcinoma, osteosarcoma, and melanoma), certain groups of patients have had longer disease-free survival produced by the use of chemotherapy after surgical removal of the primary lesion. The potential impact on cancer mortality from these treatment results is obvious. We review here the fundamental laboratory concepts that have led to human trial of multimodal primary therapy regimens. Data from numerous clinical trials are analyzed, with delineation of the problems encountered in the interpretation of their results.

Animals↗
PubMed2002

Multimodal quantal release at individual hippocampal synapses: evidence for no lateral inhibition.

Most CNS synapses investigated thus far contain a large number of vesicles docked at the active zone, possibly forming individual release sites. At the present time, it is unclear whether these vesicles can be discharged independently of one another. To investigate this problem, we recorded miniature excitatory currents by whole-cell and single-synapse recordings from CA3-CA1 hippocampal neurons and analyzed their stochastic properties. In addition, spontaneous release was investigated by ultrastructural analysis of quickly frozen synapses, revealing vesicle intermediates in docking and spontaneous fusion states. In these experiments, no signs of inhibitory interactions between quanta could be detected up to 1 msec from the previous discharge. This suggests that exocytosis at one site does not per se inhibit vesicular fusion at neighboring sites. At longer intervals, the output of quanta diverged from a random memoryless Poisson process because of the presence of a bursting component. The latter, which could not be accounted for by random coincidences, was independent of Ca2+ elevations in the cytosol, whether from Ca2+ flux through the plasma membrane or release from internal stores. Results of these experiments, together with the observation of spontaneous pairs of omega profiles at the active zone, suggest that multimodal release is produced by an enduring activation of an integrated cluster of release sites.

Animals↗
PubMed2002

Anatomical evidence of multimodal integration in primate striate cortex.

The primary visual cortex (area 17 or V1) is not thought to receive input from nonvisual extrastriate cortical areas. However, this has yet to be shown to be the case using sensitive tracers in the part of area 17 subserving the peripheral visual field. Here we show using retrograde tracers that peripheral area 17 subserving the visual field at an eccentricity of 10-20 degrees receives projections from the core and parabelt areas of the auditory cortex as well as from the polysensory area of the temporal lobe (STP). The relative strength of these projections was calculated for each injection by computing the proportions of retrogradely labeled neurons located in the auditory and STP areas with respect to number of labeled neurons constituting the established projection from the superior temporal sulci (STS) motion complex (middle temporal area, medial superior temporal, fundus of the superior temporal area). In peripheral area V1 the projection from auditory cortex corresponds to 9.5% of that of the STS motion complex and STP to 35% of that from the STS motion complex. Compared to peripheral area 17, central and paracentral area 17 showed considerably weaker inputs from auditory cortex (0.2-0.8%) but slightly more from STP cortex (3.5-6.1%). The present results show that the connectivity of area 17 is eccentricity dependent. Direct projections from auditory and STP cortex to peripheral area 17 have important consequences for higher visual functions of area 17, including multimodal integration at early stages of the visual cortical pathway.

Animals↗
PubMed1999

Results of surgery and multimodal therapy for patients with soft tissue sarcoma invading to vascular structures.

BACKGROUND: The aim of this study was to analyze the impact of resection and reconstruction of major vessels on the limb salvage rate, local disease free survival, and overall survival for patients with soft tissue sarcomas invading to neurovascular bundles. METHODS: Twenty patients were treated in a 7-year period by one surgical team. Preoperative therapy consisted of isolated limb perfusion (n = 6), systemic chemotherapy (n = 4), systemic chemotherapy combined with regional hyperthermia (n = 2), and external beam irradiation (n = 1). All patients underwent resection of the sarcoma monobloc together with the neurovascular bundle invaded. Vessels were replaced by an autologous vein transplant or an allograft, and, in six patients, a myocutaneous flap or skin graft had to be used for soft tissue coverage. RESULTS: Histologic examination revealed negative histologic margins (R0-resection) and infiltration of the neurovascular bundle in all patients. In four patients, a local recurrence was observed, and, in three of them, reresection with negative margins was achieved. The mean local recurrence free survival was 54 months (confidence interval [CI], 42-66 months), and the mean overall survival was 48 months (CI, 32-57 months). Limb salvage was achieved in 19 of 20 patients. Eleven patients developed distant metastases after a mean survival time of 30 months. CONCLUSIONS: Extended sarcoma resection, including vessel replacement after preoperative multimodal therapy, provides long term local control and limb salvage. Amputation of extremity sarcoma can hardly be justified, even in cases of tumor invasion to neurovascular bundles. However, efforts to achieve better control over systemic spread are required for long term disease free survival.

Adult↗
PubMed1986

The development of a freestanding adolescent partial-hospitalization program in a multimodal integrated-service system for high-risk youth.

At Three Rivers Youth in Pittsburgh, a freestanding adolescent partial-hospitalization program is a primary force in a multimodal integrated-treatment system for high-risk youth. Three barriers encountered in the development of the program (utilization, integration with other components, and staffing) are discussed and strategies successful in overcoming these barriers are presented. Features of the program which are believed to contribute to its success are outlined, including scheduling, clinical structures, educational services, case management, and staffing. Case illustrations from clinical practice in the program are also offered.

Adolescent↗
PubMed1998

Concepts of a Web-based open distributed textbook for the multimodal diagnostics of gastrointestinal tumours with MRI, CT and video-endoscopy addressing students of medicine and students of medical informatics as two different target groups.

Multimodal diagnostics of gastrointestinal tumours with MRI, CT and video-endoscopy is a rapidly changing domain. The education at our universities should overcome the obstacles of traditional learning based on paper media and oral lectures with retention rates of 10-30% only. The paper presents the objectives and the results of the design phase of the project ODITEB1-Open Distributed TExt Book, for Computer-Assisted Instruction in the domain mentioned above. The main objective is to produce an electronic interactive textbook in order to shift education to more efficient learning settings with higher retention rates. The main concepts are 1) three-layer architecture (dynamic case layer, intermediate query layer, static instruction layer) 2) case pool distribution 3) active learners experience (interactive exploration of original image data).

Computer-Assisted Instruction↗
PubMed1996

Multimodality Therapy for Esophageal Cancer.

Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with esophageal cancer. A series of randomized prospective trials has convincingly demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a survival advantage after a complete tumor resection. The available data on the role of neoadjuvant preoperative therapy in patients with adenocarcinoma or squamous cell carcinoma of the esophagus are not yet conclusive. While neoadjuvant therapy may undoubtedly reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, i.e., potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e., tumors in which a complete tumor removal with primary surgery appears unlikely, neoadjuvant therapy allows a marked downstaging of the primary tumor and thus significantly increases the chance for complete tumor removal on subsequent surgery. However, only patients with objective clinical or histopathological response to preoperative therapy appear to benefit from this approach. Compared with preoperative chemotherapy alone, combined radiochemotherapy increases the rate of response but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently be performed only in experienced centers within the context of clinical trials. The identification of factors which would facilitate prediction of the response to neoadjuvant therapy is currently the focus of several studies. Furthermore, more effective and less toxic preoperative therapy regimens are required to increase the response rates and combat systemic recurrences.

Journal Article↗
PubMed1999

[Multimodal therapy concepts in esophageal carcinoma: importance of radio- and chemotherapy].

Five-year survival of surgically treated patients with operable oesophageal carcinoma does not exceed 20%. The results with curative radiotherapy are even worse, with < or = 10% alive after 5 years. New treatment strategies are needed. Pre- or postoperative radiotherapy and perioperative chemotherapy alone do not improve survival. A simultaneous radiochemotherapy with cisplatin is significantly more effective than radiotherapy alone. A subgroup of patients with pathological complete remission after preoperative treatment (radio- and/or chemotherapy) survives significantly longer. It seems likely that survival in oesophageal cancer is improved by multimodal therapy encompassing radiotherapy, chemotherapy and surgery. Further randomised trials are needed, possibly in combination with other potentially active drugs.

Antineoplastic Agents↗
PubMedDate not supplied

Surgical and multimodal approaches to cancer of the oesophagus: state of the art.

This review article aims to discuss the modalities of oesophageal resection, to define the categories of patients who are most likely to benefit from oesophagectomy with extensive lymph node clearance, and to analyse the eventual contribution of nonsurgical neo-adjuvant or adjuvant therapies to improving long-term survival rates achieved by surgery alone. Both the review of the literature devoted to potentially curative treatment of oesophageal cancer and the authors' own experience indicate that resection of the oesophageal tube en bloc with the locoregional lymph nodes provides patients with the best chance of long-term survival and cure. This is true, even though some of the resected lymph nodes are metastatic. Most phase III comparative studies fail to shown any overall survival improvement following multimodal therapy in comparison with surgery alone, so that there is now no scientific reason for systematic addition of radio- and/or chemotherapy to extensive surgery in potentially resectable neoplastic processes. However, neo-adjuvant radio- and/or chemotherapy is indicated in suspected non-resectable T4 tumors for downstaging and subsequent oesophageal resection in good responders. The benefit in terms of long-term survival and cure that can be expected from adjuvant chemo- and/or radiotherapy after radical resection of a neoplastic process having already spread into a large number of loco-regional lymph node requires objective evaluation by prospective, randomized studies.

Combined Modality Therapy↗
PubMed1999

Integration and visualization of multimodality brain data for language mapping.

A goal of the University of Washington Brain Project is to develop software tools for processing, integrating and visualizing multimodality language data obtained at the time of neurosurgery, both for surgical planning and for the study of language organization in the brain. Data from a single patient consist of four magnetic resonance-based image volumes, showing anatomy, veins, arteries and functional activation (fMRI). The data also include the location, on the exposed cortical surface, of sites that were electrically stimulated for the presence of language. These five sources are mapped to a common MR-based neuroanatomical model, then visualized to gain a qualitative appreciation of their relationships, prior to quantitative analysis. These procedures are described and illustrated, with emphasis on the visualization of fMRI activation, which may be deep in the brain, with respect to surface-based stimulation sites.

Anatomy, Cross-Sectional↗
PubMed2000

[A case of recurrent pancreatic cancer brought into a complete response by a multimodal treatment with intraarterial chemotherapy and radiotherapy].

We achieved a complete response of recurrent pancreatic cancer using a multimodal treatment with intravenous, oral and intraarterial chemotherapies and radiotherapy. A 55-year-old female patient had a recurrent pancreatic cancer, which had invaded the portal vein, 2 years after pancreatoduodenectomy. Angiography demonstrated prominent stenosis of the portal vein, which was enlarged by the insertion of a metalic stent to maintain blood flow to the liver. Chemotherapy included intravenous mitomycin C, 5-FU and 4'-epirubicin (EPI), oral UFT and cyclophosphamide, and intraarterial cisplatin, 5-FU and EPI through a catheter inserted into the celiac artery. Furthermore, the patient received a total of 50 Gy radiotherapy. Four months after the initiation of therapy, a computed tomography image demonstrated a complete disappearance of the recurrent tumor and a prominent decrease in the serum CA19-9 level. At present, 11 months have passed after the initiation of therapy, and she has been followed at our outpatient department without any symptoms of recurrence.

Adenocarcinoma↗
PubMed2000

[Memory advantage of performed actions: comments on multimodal memory theory].

Based on the integration of the memory advantage for subject-performed actions into the multimodal theory of episodic memory by J. Engelkamp (1997), three issues referring to the so-called enactment effect are discussed and addressed by statistical r-analyses. Firstly, the empirical basis of the functional distinction between motor and non-motor memory resources by means of dual-task experiments is questioned. Secondly, a multinomial modeling analysis is presented which aims at the contributions of automatic and controlled memory processes to the enactment effect in the process-dissociation paradigm. Finally, the effect of enactment on memory for serial order information is discussed with respect to recent accounts of serial memory.

Attention↗
PubMed2000

Development of multimodal attention in young infants: modification of the startle reflex by attention.

This study examined the effect of attention engagement to compound auditory-visual stimuli on the modification of the startle blink reflex in infants. Infants at 8, 14, 20, or 26 weeks of age were presented with interesting audiovisual stimuli. After stimulus onset, at delays defined by heart rate changes known to be associated with sustained attention or attention disengagement, blink reflexes were elicited by visual or auditory stimuli. Blink amplitude to either visual or auditory stimuli was enhanced when the infants were engaged in attention to the foreground auditory-visual stimuli relative to control trials with no foreground patterns. This enhancement of the blink amplitude increased from 8 to 26 weeks of age. In contrast to selective modality enhancement for single-modality foreground stimuli, these results show that these multimodal stimuli engage both visual and auditory attention systems in this age range.

Acoustic Stimulation↗
PubMed2000

[Early intervention in increased risk for schizophrenic illnesses. Multimodal psychotherapy--antipsychotic drugs only in treatment failure].

Interventional strategies for the prodromal phase of schizophrenia are based largely on treatment concepts that have already been shown to be effective for the prevention of relapses. Such a multimodal concept for early psychotherapeutic intervention has been developed at the psychiatric department of the University of Cologne. This model emphasizes individual symptom-oriented cognitive/behavioral treatment and psychoeducation directed both to the patient and his/her contact person(s). In addition, stress and symptom management, training of social skills and computer-aided cognitive training tailored to individual needs are also offered. In contrast, pharmacological treatment is considered only when, despite the above-mentioned strategy, the clinical picture worsens appreciably and attenuated psychotic symptoms have appeared.

Antipsychotic Agents↗
PubMedDate not supplied

Multimodality therapy in surgically resectable early non-small cell lung cancer.

Lung cancer is a global epidemic. Unfortunately only a fraction of patients can undergo curative surgery and in these, only one-third survive five years. The remainder die of locoregional and distant metastatic disease. With advances in chemotherapy for systemic control and radiation therapy for local control, responses and survivals have shown promise in extensive inoperable disease. In order to attempt to extend survival in extensive local but operable disease (Stage IIIa), these treatment modalities were added to the surgical regimen either before (neoadjuvant, induction) or after (adjuvant) surgery. Several small phase III trials substantiated the benefits. Since early lung cancer (Stage I and II) recur in 30% of instances to distant sites as well as regionally, multimodality therapies have recently been encouraged in global trials in an attempt to prolong time to recurrence and survival in this latter group of patients. A review follows:

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients.

BACKGROUND: Standard endosonographic (EUS) staging criteria are unreliable for staging esophageal carcinoma after neoadjuvant therapy; however, measurement of tumor size reduction can identify patients who have achieved a pathologic response. In the current study the authors prospectively compared survival between patients classified as responders and those classified as nonresponders by EUS. METHODS: The maximal transverse cross-sectional area of the tumor was measured before and after neoadjuvant therapy in patients who were candidates for multimodality treatment. Response was defined as a > or = 50% reduction in tumor area. RESULTS: A total of 59 patients at 2 centers were followed for a median of 19 months. EUS assessed response in 34 patients (58%). Overall, responders had a median survival of 17.6 months compared with 14.5 months for nonresponders (P < 0.005). Survival was significantly longer in responders compared with nonresponders in the patient subgroup who underwent surgical resection (19.7 months vs. 14.6 months; P < 0. 005), the patient subgroup with adenocarcinoma (21.4 months vs. 10.8 months; P < 0.005), and the patient subgroup initially classified as having T3N1 disease (17.6 months vs. 14.1 months; P < 0.05). Survival was not found to differ significantly between responders and nonresponders in the subgroup of patients with squamous cell carcinoma. EUS response was the only clinical variable that was associated with survival time in a multivariate analysis (relative hazard = 0.27; P < 0.005). CONCLUSIONS: Patients with esophageal carcinoma who respond to neoadjuvant treatment as identified by EUS measurement of reduction in tumor size have a significantly better prognosis than nonresponders.

Adenocarcinoma↗
PubMed2000

Multimodality therapy of esophageal cancer: an update.

The incidence of adenocarcinoma of the esophagus is rapidly increasing in Western countries, particularly in Caucasian men. Both squamous cell carcinoma and adenocarcinoma are equally virulent tumors. In the absence of effective prevention and screening programs, most Western patients are found to have locally advanced or metastatic disease at the time of diagnosis. The outcome with regional therapy alone (either surgery or radiation) is poor. Multimodality therapy--treatment plans which include both systemic and regional treatments-is the focus of intense study. This review will summarize the current status of several different approaches that have the goal of increasing the cure rate in patients with newly diagnosed esophageal cancers.

Adenocarcinoma↗
PubMed2000

PACS and multimodality in medical imaging.

A PACS (Picture Archiving and Communication System) is a system that is able to store, exchange, display and manipulate images and associated diagnoses from any modality within a hospital in a timely and cost-effective way. Several developments, such as the DICOM standard, fast and convenient networking, and new storage solutions for large amounts of data, make the setup of such a PACS system possible. As the information acquired with various imaging modalities is then available and often complementary, it is desirable for the clinician to have a point-by-point spatial co-registration of images from different modalities in order to enable a synergistic use of the multimodality imaging of a patient for increased diagnostic accuracy. Various types of algorithms are available for the matching of medical images from the same or from different modalities. Co-registration algorithms based on voxel properties consist of a similarity or dissimilarity measure and an iterative or non-iterative method minimizing the dissimilarity or maximizing the similarity between the two images by a transformation of one image relative to the other.

Belgium↗