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[Synovial sarcoma of the extremities. Results of surgical and multimodal therapy].

BACKGROUND: Synovial sarcoma is a rare tumor frequently occurring in adolescents and young adults. The preferred location, at the distal parts of the extremities, and the high incidence of distant metastases represent major challenges for treatment. The purpose of this study is to analyze the indications for surgery in the context of a multimodal therapy. PATIENTS AND METHODS: Between October 1992 and December 2000, 41 patients were treated surgically for synovial sarcoma of the extremities. Their mean age was 35 years (range: 11-75 years). Extracompartmental tumor growth was present in more than 90% of the patients. Fourteen patients (34%) presented with a tumor size of less than 5 cm (T1) while 27 patients (66%) showed lesions greater than 5 cm (T2). At the time of presentation, seven patients had distant metastases; three located in the lung and four in lymph nodes. RESULTS: Due to a locally unresectable tumor or synchronous distant metastases, 28 patients (68%) underwent preoperative systemic chemotherapy (n=9) or isolated limb perfusion (n=18) or both (n=1). In 29 patients, limb-conserving surgery was possible. Of the 12 patients (29%) who required amputation, 85% had a distal tumor. Sixteen patients received additional postoperative radio- and/or chemotherapy. After a median follow-up of 30 months, only two patients (7%) had developed a local recurrence, while seven patients (20%) suffered from new, distant metastases. The 5-year overall survival rate was 82%. CONCLUSION: With a combined modality treatment, it is possible to achieve excellent local control rates and long-term survival in patients with synovial sarcoma of the extremities. Neoadjuvant treatment can enable limb-sparing surgery in most patients, even if the tumors are located in anatomically difficult areas.

Adolescent↗

[Multimodal therapy of tumors of the upper gastrointestinal tract].

Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with carcinoma of the upper gastrointestinal tract. A series of randomized prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in gastric or esophageal cancer. The available data on the role of neoadjuvant preoperative therapy in these patients as yet permit no conclusion. While neoadjuvant therapy may reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that, compared to primary resection, a multimodal approach does not result in a survival benefit in patients with loco-regional, i.e. potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e. tumors for which complete removal with primary surgery appears unlikely, neoadjuvant therapy increases the chance for complete tumor resection on subsequent surgery. However, only patients with objective histopathologic response to preoperative therapy appear to benefit from this approach. Compared to preoperative chemotherapy alone, combined radio-chemotherapy increases the rate of response, particularly in squamous cell esophageal cancer, but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently only be performed in experienced centers within the context of prospective clinical trials. The identification of factors that would allow prediction of response to neoadjuvant or adjuvant therapy is the focus of ongoing studies.

Adenocarcinoma↗

[Multimodal therapy of rectal carcinoma].

Multimodal therapy for rectal carcinoma is--in contrast to colon cancer--largely based on adjuvant or neoadjuvant radiotherapy. Although radiotherapy reduces local recurrence rates, overall survival is hardly improved, while on the other hand specific complications of radiotherapy are recognized. Extended neoadjuvant treatment concepts including chemotherapy may improve long-term outcome, but to date this has not been demonstrated conclusively by randomized trials. New developments include intraoperative radiotherapy and the combination of hyperthermia with radiochemotherapy. Initial results from randomized studies are promising, but require confirmation by larger trials. At the same time the importance of optimal surgical treatment has been recognized as a prerequisite for favourable long-term results. Since this aspect has not received due attention in past protocols the optimal combination of surgery with other modalities and their time sequence cannot be determined presently.

Chemotherapy, Adjuvant↗

[Intraoperative radiotherapy as multimodal therapy approach in epithelial tumors of the gastrointestinal system].

Surgery alone often fails to achieve local control in advanced gastrointestinal tumors. With multimodal therapy approaches, both local tumor control and long-term survival appear to be improved. Intraoperative radiation therapy (IORT) is an attempt to achieve higher doses of irradiation while dose-limiting structures are surgically displaced. It has been shown previously that both local tumor control and long-term survival are improved in patients undergoing surgery combined with IORT for both primary and recurrent rectal carcinoma. In advanced gastric carcinoma, IORT has achieved optimistic survival results in a few studies. In locally advanced pancreatic cancer, an apparent improvement in local control has been noted with IORT, but survival has not been prolonged because of a high incidence of both liver and peritoneal metastases. The data concerning IORT for esophageal carcinoma are not yet sufficient to allow judgement.

Animals↗

[Surgical and multimodal therapy of pseudomyxoma peritonei].

The rarity of Pseudomyxoma peritonei, its complex biology and the remaining inconsistencies in terminology all contribute to rendering therapeutic recommendations a difficult task. In principle, a multimodal concept combining cytoreductive surgery with peri- and postoperative intraperitoneal chemotherapy constitutes the preferable treatment. Initially, surgical peritonectomy aims to achieve the complete removal of tumor cells at the macroscopic level. Subsequently in the early postoperative phase when the absence of adhesions allows for a homogeneous intraabdominal spread of cytotoxic drugs, intraperitoneal application of 5-fluorouracil and mitomycin C represents the most solidly established treatment. Therapeutic failures are often due to insufficiently radical cytoreductive surgery or a lack of homogeneous distribution of cytotoxic drugs in the abdomen. In view of the rarity of their condition, patients with Pseudomyxoma peritonei should be treated at or in conjunction with specialized centers. Only such a "center-oriented" approach will secure the standardization of treatment and help to clarify unsettled therapeutic questions. The development of improved therapeutic concepts will depend on concise histopathological classification. Already at present therapeutic decisions should not only be be based on the clinical aspect of a "mucinous abdomen" but should be guided by the pathological differentiation between disseminated peritoneal adenomucinosis (DPAM), with a relatively good prognosis, and the more aggressive peritoneal mucinous carcinomatosis (PMCA).

Chemotherapy, Adjuvant↗

[A case of delusional parasitosis in severe heart failure. Olanzapine within the framework of a multimodal therapy].

The case of a 73-year-old male with delusions of parasitosis (DP) is presented. He complained about severe itching of the limbs and the genital region as well as abnormal body and pubic hair that he believed to be parasites. The symptoms occurred over the course of several years together with severe heart diseases (New York Heart Association class III, atrial fibrillation, tricuspid regurgitation) and chronic edema of the lower leg. The pruritus was also based on chronic, self-induced skin lesions due to aggressive disinfection and tearing out of body hair. After ruling out true infection, a multimodal DP therapy was initiated. Instead of the standard neuroleptic drug pimozide, olanzapine was used because of its better tolerability in patients with increased cardiac risk (i.e., borderline prolonged QTc time). At discharge, the DP had partially remitted. Substantial improvement in the heart and skin diseases under specific treatment contributed substantially to the success of the therapeutic regimen. This case hints at (1) the effectiveness of olanzapine in DP and (2) the importance of general medical conditions in the therapeutic approach to DP.

Aged↗

[Multimodal computed tomography in acute cerebral infarction. Experience with a standardized protocol in 100 patients].

Computed tomography (CT) is the standard method of brain imaging in acute stroke. To an experienced examiner, nonenhanced CT will exclude hemorrhage and may indicate early ischemic signs. Reliable description of an ischemic area and the underlying vascular disease is not possible in the acute phase but is possible, particularly within the first hours, when therapeutic decisions on matters such as systemic thrombolysis are to be made. For such rapid decision-making, imaging must provide more information. Novel, contrast-enhanced CT techniques can provide this information. Perfusion CT (CTP) can show brain perfusion, allowing one to distinguish between reversible and irreversible damage in an ischemic area. Also, CT angiography (CTA) can detect occlusion or stenosis in the relevant vasculature. Using a modern, multislice CT scanner, it is now possible to combine these modalities of imaging. In a fast protocol for emergency evaluation, all three methods can be performed and evaluated to provide the crucial information within 15 min. In the first 102 patients examined within 6 h of symptom onset using this protocol, multimodal CT contributed substantially to therapeutic decisions, even though there are some limitations in these methods.

Acute Disease↗

[Multimodal diagnosis of multiple and heterogeneous liver lesions in a young patient].

The classification of liver lesions is often problematic in particular if they are multiple and show an heterogeneous shape. Here we report of a young patient with multiple liver lesions of up to 3 cm size. Using ultrasound, the lesions were hyper-, hypoechogen or mixed. In serial contrast enhanced CT scans some of the lesions showed the typical enhancement pattern of hemangiomas, however, the diagnosis could still not be faithfully determined for all lesions. Therefore, the patient was conducted to contrast enhanced MRI (Gd-DTPA and MnDPDP). While with Gd-DTPA some of the lesions showed a strong enhancement, they remained hypointense after administration of MnDPDP. Finally to exclude a metastatic disease a (99m)Tc-erythrocyte SPECT was performed confirming the diagnosis of hemangiomas for most of the lesions. Diagnosis was not assessed by biopsy because this would only clarify the diagnosis for one or few of the lesions. The patient was subsequently followed up for 3 years and all lesions remained unchanged. This case clearly illustrates the difficulty to get a certain diagnosis of multiple liver lesions with heterogeneous appearance despite the multimodal diagnostic conduct.

Adult↗

Multimodal inputs to the granule cell domain of the cochlear nucleus.

There is growing evidence that hearing involves the integration of many brain functions, including vision, balance, somatic sensation, learning and memory, and emotional state. Some of these integrative processes begin at the earliest stages of the central auditory system. In this review, we will discuss evidence that reveals multimodal projections into the granule cell domain of the cochlear nucleus.

Animals↗

Multimodal mechanisms of attention related to rates of spatial shifting in vision and touch.

Covert attention can be directed spatially in several different sensory modalities (e.g. vision and touch). Recent psychological experiments indicate the existence of crossmodal links in spatial attention, but their neural basis in humans remains underspecified. We used positron emission tomography (PET) to assess the role of stimulus modality in the activity of brain regions involved in different rates of spatial attention shifting. A 2 x 2 factorial design manipulated the rate (high versus low) of spatial attention shifts between left and right hemifields, plus the sensory modality (vision versus touch) of stimulation. Two brain regions showed activations related to attentional shift-rate, independent of the stimulated modality: these were the right frontopolar gyrus, and the right posterior superior temporal sulcus (STS). The anterior area showed higher blood flow with the high rate of shifts in spatial attention, while the posterior area showed higher flow during the low rate conditions, where attention was sustained for longer on one side. No area showed a significant rate effect in one modality without an effect in the second modality. These results demonstrate multimodal roles for the activated brain regions in relation to the rate of spatial attention shifting, plus right-hemisphere dominance for this. They also suggest that anterior and posterior regions of the spatial-attention network play different roles in attention shifting.

Adult↗

Multimodal MR examination in acute ischemic stroke.

In recent years, combined diffusion-weighted imaging (DWI) with perfusion imaging (PI) has become an important investigational tool in the acute phase of ischemic stroke, as it may differentiate reversible from irreversible brain tissue damage. We consecutively examined 20 subjects within 12 h of stroke onset using a multiparametric magnetic resonance (MR) examination consisting of DWI, mean transit time (MTT) as PI parameter, and MR angiography (MRA). T2-weighted and fluid-attenuated inversion recovery (FLAIR) on day 7 were also acquired in order to obtain final infarct volume. The following MR parameters were considered: volumetric measures of lesion growth and MTT abnormalities, quantification of regional apparent diffusion coefficient (ADC) and visual inspection of MRA findings. Our results showed: (1) an acute DWI lesion was not predictive of lesion growth and the DWI abnormality did not represent the irreversibly infarcted tissue; (2) ADC values in the ischemic penumbra could not predict tissue at risk; (3) the DWI-PI mismatch did not predict lesion growth, and the PI abnormality overestimated the amount of tissue at risk; and (4) patients with proximal middle cerebral artery occlusion had greater initial and final infarct volumes. This study did not demonstrate the prognostic value of a multimodal MR approach in early ischemic stroke; MRA alone provided predictive information about the volumetric evolution of the lesion.

Acute Disease↗

Multimodal visualization interface for data management, self-learning and data presentation.

A multimodal visualization software, called the Data Manager (DM), has been developed to increase interdisciplinary communication around the topic of visualization and modeling of various aspects of the human anatomy. Numerous tools used in Radiology are integrated in the interface that runs on standard personal computers. The available tools, combined to hierarchical data management and custom layouts, allow analyzing of medical imaging data using advanced features outside radiological premises (for example, for patient review, conference presentation or tutorial preparation). The system is free, and based on an open-source software development architecture, and therefore updates of the system for custom applications are possible.

Anatomy↗

Malignant thymoma: current status of classification and multimodality treatment.

Classification, understanding of the pathophysiology, and treatment options of thymoma have changed during recent years. It is hoped that novel strategies will lead to a survival benefit in these patients. It has become clear that patients with thymoma are best treated with multimodality therapy. In this review, a pathologist, an immunologist, a surgeon, a radiotherapist, a pneumologist, and oncologists discuss the current status of classification and strategies for the treatment of patients with thymoma.

Clinical Trials as Topic↗

Multimodal biochemical modulation of 5-fluorouracil by leucovorin, methotrexate, and interferon alpha in patients with advanced colorectal cancer.

A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i.v. on days 1-4; 400 mg/m2 5-fluorouracil i.v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i.v. on days 2, 3, 5, and 6. Interferon-alpha 2b at a dose of 3 million U was given i.m. daily for the 6 days of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence interval 2-28%): In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to be effective, as it results in severe toxicity.

Adult↗

Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: is there a benefit in using functional imaging?

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and (18)F-FDG-PET (n=23) before and 2-4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60+/-14%) was significantly higher than in nonresponders (37+/-31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.

Adenocarcinoma↗

Tuberous sclerosis: epileptogenicity and multimodal presurgical evaluations.

We report on a patient with tuberous sclerosis-related epilepsy who benefited from surgical treatment. Various presurgical evaluations, including positron emission tomography (PET), made it possible for us to localize the epileptic focus accurately. In this paper, we stress the importance of performing multimodal evaluations to determine which tubers really possess epileptogenicity. In addition, the implications of PET in tuberous sclerosis-related epilepsy are described.

Cerebral Cortex↗

[The multimodal rheumatologic complex treatment (OPS 8-983)--challenges, solutions and perspectives].

As from 2005 the specialized complex rheumatologic treatment can be assigned to the code category 8-983 (Multimodale rheumatologische Komplexbehandlung) of the OPS procedure classification system. Only by means of this specific procedure code, has an appropriate description and consideration in the G-DRG system of the common clinical practice in specialized rheumatologic hospitals/clinics become possible. The complex and multimodal treatment reflects the rheumatologic therapeutic standard for the treatment of inflammatory rheumatic diseases and non-inflammatory pain syndromes. The article focuses on the minimal criteria that have to be met for coding the OPS 8-983. Helpful practical instructions are given concerning how to implement the complex procedure into practice. Even though the newly introduced procedure code OPS 8-983 will not yet develop influence on the grouping process in 2005, other changes in the GDRG system lead to an improved economic valuation of rheumatological services in comparison to 2004.

Diagnosis-Related Groups↗

Clinical response to induction chemotherapy predicts local control and long-term survival in multimodal treatment of patients with locally advanced esophageal cancer.

PURPOSE: From 1991 to 1994 we performed a phase II study with intensive preoperative chemoradiation in locally advanced squamous cell carcinoma and adenocarcinoma of the esophagus. We now report on a multivariate analysis of prognostic factors based on the long-term results at a median follow-up of 6.5 years. PATIENTS AND METHODS: Eighty-eight patients were treated. Prognostic factors for overall survival and local tumor control were identified by univariate and multivariate analysis. RESULTS: Median overall survival reached 17 months, and the survival rate at 5 years was 22% (95%-confidence interval: 18-26%). Response to induction chemotherapy was the only independent factor predicting local tumor control and--beside weight loss prior to treatment--it also proved to be an independent prognostic factor for long-term survival. CONCLUSIONS: Intensive chemoradiation followed by surgery seems to be appropriate to improve long-term survival of high-risk patients with locally advanced esophageal cancer. In our trial, local tumor control and prognosis were best correlated with response to induction chemotherapy. These results may help to guide decisions regarding surgery in multimodal treatment of EC. Further efforts are needed to increase the number of treatment responders and to predict tumors not responding to chemo(radio)therapy earlier.

Adenocarcinoma↗