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[Polymer-drug complexes in the treatment of extensive ovarian cancer].

The paper presents the results of intracavitary chemotherapy with deposited cytostatics of advanced ovarian cancer as well experimental, morphological, biochemical and pharmacological data. Intraabdominal introduction of microspheres filled with cyclophosphamide, 5-fluorouracil, doxorubicin can be a variant of drug therapy in multimodality treatment of ovarian cancer. Combination of intracavitary chemotherapy with a systemic one has the advantage of local and regional effect which is not inhibited by mediated action of the deposited cytostatics via the systemic blood flow. The method is indicated in residual tumor dissemination after cytoreductive surgery and ovarian cancer with ascites.

Adult↗

[Intraoperative radiotherapy in advanced soft tissue sarcoma of the extremities].

Radical or wide excision is the treatment of choice for soft-tissue sarcomas (STS) of the extremities. Multimodality therapy made limb-sparing surgery possible. While external beam radiotherapy is well established in this setting, few data are available about intraoperative radiotherapy (IORT). We performed an analysis of 36 patients treated with IORT and external beam radiation following resection of STS of the extremities between 1991 and 1995. Only STS classified as UICC stage IIb, III or IV were included. Operative morbidity was 17%, 14% showed late complications. Within a mean follow-up of 24 months (min. 6), there was one local recurrence in 30 patients treated curatively. The 3-year survival rate of patients treated curatively was 75%; 3-year recurrence-free survival was 65%.

Combined Modality Therapy↗

Large strain behaviour of brain tissue in shear: some experimental data and differential constitutive model.

In this paper, some experimental measurements of the behaviour of bovine brain tissue under large shear strains in vitro are reported, and a constitutive model which is consistent with the data is developed. It was determined that brain tissue is not strain-time separable, showing slower relaxation at higher strains, and that the stresses in shear are not linear with increasing shear strain. The new constitutive model is a differential model, including both an "elastic" term, of the Mooney type and a nonlinear viscoelastic term. The latter allows for the change in relaxation behaviour with strain, by modifying an upper convected multimode Maxwell model with a damping function. The model shows good agreement with the experimental shear results and could be used to describe other types of data.

Animals↗

[Status of gastrectomy in the multi-modality therapy concept of primary non-Hodgkin's lymphoma of the stomach].

Retrospectively analyzed data of 41 patients with gastric non-Hodgkin lymphoma are presented with special regard to the required extent of gastric resection in multimodality treatment. Thirty lymphomas of low, 2 of intermediate and 9 of high grade malignancy were distributed on stage Ie in 44%, stage IIe in 15%, stage IIIe in 12% and stage IV in 29%. The cumulative 5 years survival rate was 85% for stage Ie and 55% for the stages IIe and IIIe. Stage IV showed a 3 years survival of 10%. The proximal part of the stomach was involved in 73%, polycentric lesions were found in 15%. The majority (71%) of the tumours showed an infiltrating growth, an invasion of the oesophagus and/or the duodenum was seen in 20%. Five patients (12%) had synchronous adenocarcinoma as second gastric tumour. Regarding our morphological and topographical data curative surgery for primary gastric lymphoma required total gastric resection.

Adult↗

Simultaneous multimode experiments for studies of electrochemical reaction mechanisms: demonstration of concept.

An instrumental setup has been configured for a simultaneous real time recording of electrochemical, spectroelectrochemical, and mass data on an electrode from a single measurement for studies of complex electrochemical reaction mechanisms. This was achieved by combining a few pieces of equipment: a potentiostat/galvanostat for electrochemical measurements, the near-normal incidence reflectance spectrometer for spectroelectrochemical measurements, and a quartz crystal analyzer (QCA) for mass changes on the electrode. The latter two were coupled through a bifurcated optical fiber on the reflective QCA electrode. The experimental setup thus assembled was demonstrated to be very powerful in elucidating reaction mechanisms of the reaction sequence for a complex reaction, for example, electrochemical oxidation of aniline, which accompanies spectral, as well as weight, changes upon oxidation. The system was also applied to the study of the lithium intercalation reaction of tungsten trioxide thin films in a nonaqueous solution.

Journal Article↗

The role of multimodality therapy in soft-tissue sarcoma.

Soft-tissue sarcomas are uncommon malignancies. The development during a period of 8 years, in one institution, of a prospective data base incorporating more than 1600 patients with these tumors is described. The most common sites for occurrence are the extremities, but they can occur in any of the soft tissues of the body. Liposarcoma and leiomyosarcoma are the most common histopathologic conditions identified. Prognostic factors for both recurrence and survival include site, histopathology, size, grade, and adequacy of resection. A prospective randomized trial of the use of adjuvant radiation by the brachytherapy technique in extremity lesions has shown a decrease in local recurrence, but no impact on survival. Eligible patients not randomized to the trial show no difference in local recurrence or survival, regardless of whether they received adjuvant radiation.

Adolescent↗

Multimodal MR imaging: functional, diffusion tensor, and chemical shift imaging in a patient with localization-related epilepsy.

PURPOSE: To demonstrate the integration of complementary functional and structural data acquired with magnetic resonance imaging (MRI) in a patient with localization-related epilepsy. METHODS: We studied a patient with partial and secondarily generalized seizures and a hemiparesis due to a malformation of cortical development (MCD) in the right hemisphere by using EEG-triggered functional MRI (fMRI), diffusion tensor imaging (DTI), and chemical shift imaging (CSI). RESULTS: fMRI revealed significant changes in regional blood oxygenation associated with interictal epileptiform discharges within the MCD. DTI showed a heterogeneous microstructure of the MCD with reduced fractional anisotropy, a high mean diffusivity, and displacement of myelinated tracts. CSI demonstrated low N-acetyl aspartate (NAA) concentrations in parts of the MCD. CONCLUSIONS: The applied MR methods described functional, microstructural, and biochemical characteristics of the epileptogenic tissue that cannot be obtained with other noninvasive means and thus improve the understanding of the pathophysiology of epilepsy.

Adult↗

Nonsurgical management of malignant thymoma.

BACKGROUND: Thymoma is a rare tumor entity. Surgery remains the mainstay of treatment, but radiation and chemotherapy also have been applied widely in both the adjuvant and the palliative setting. The objective of this study was to review briefly the clinical trials available in the current literature utilizing nonsurgical oncologic treatment (radiotherapy and chemotherapy) either in patients with advanced (i.e., locally inoperable) or metastatic thymoma or as an adjunct to surgery. METHODS: A computerized (MEDLINE) and a manual search was performed to identify articles published on this topic between 1965-1998. Only articles with an English abstract were reviewed for inclusion; information abstracted included histologic proof of diagnosis, number of patients, dose and modality of treatment, assessment of response, response rate, survival duration, and side effects. RESULTS: Seventy-one trials were identified subsequently. These included 51 chemotherapy studies in a total of 410 patients (including 19 single agent trials and 32 combination chemotherapy trials) and 20 radiotherapy studies. In the adjuvant setting, radiation appeared to result in a higher survival rate compared with historic controls as well as excellent local control in patients with advanced stage of disease, whereas no apparent benefit was observed in patients with Masaoka et al. classified Stage I disease. The large majority of chemotherapeutic studies were case reports or Phase II trials of advanced disease, whereas no prospectively randomized trials were performed. Response rates were relatively heterogeneous and ranged between 24% and 100%, not including the results published in single case reports, and response rates >50% have been found consistently with the application of polychemotherapy. In the absence of randomized trials, multimodality approaches using induction chemotherapy followed by resection and consecutive radiation have produced highly promising results in terms of resectability and long term survival, even in patients with advanced disease. CONCLUSIONS: To the authors' knowledge, there is no standard approach to advanced thymoma apart from surgery (i.e., total resection whenever possible). Despite reports of long term disease control, symptomatic palliation, and encouraging survival data, the majority of studies involved only a small number of patients and were performed in a Phase II approach. Large scale, randomized trials to elucidate the potential of multimodality approaches clearly are needed, and patients with thymoma should be included in such studies.

Antineoplastic Agents↗

Augmentation of reality using an operating microscope for otolaryngology and neurosurgical guidance.

The operating microscope is an integral part of many neurosurgery and otolaryngology procedures; the surgeon often uses the microscopic view for a large portion of the operation. Information from preoperative radiological images is often viewed only on X-ray films. The surgeon then has the difficult task of relating this information to the appearance of the surgical view. Image guidance techniques attempt to relate these two sets of information by registering the patient in the operating room to preoperative images using locating devices. Conventionally, image data are presented on a computer monitor, which requires the surgeon to look away from the operative scene. We describe a guidance system, for procedures in which the operating microscope is used, which super-imposes image-derived data upon the operative scene. We create a model of relevant structures (e.g., tumor volume, blood vessels, and nerves) from multimodality preoperative images. By calibrating microscope optics, registering the patient to image coordinates, and tracking the microscope and patient intraoperatively, we can generate stereo projections of the three-dimensional model and project them into the microscope eyepieces, allowing critical structures to be overlaid on the operative scene in the correct position. Measurements with a head phantom gave a root mean square (RMS) error of 1.08 mm, and the estimated error for a human volunteer is between 2 and 3 mm. Initial evaluation in the operating room was very promising.

Computer Simulation↗

High-efficiency peptide analysis on monolithic multimode capillary columns: Pressure-assisted capillary electrochromatography/capillary electrophoresis coupled to UV and electrospray ionization-mass spectrometry.

High-efficiency peptide analysis using multimode pressure-assisted capillary electrochromatography/capillary electrophoresis (pCEC/pCE) monolithic polymeric columns and the separation of model peptide mixtures and protein digests by isocratic and gradient elution under an applied electric field with UV and electrospray ionization-mass spectrometry (ESI-MS) detection is demonstrated. Capillary multipurpose columns were prepared in silanized fused-silica capillaries of 50, 75, and 100 microm inner diameters by thermally induced in situ copolymerization of methacrylic monomers in the presence of n-propanol and formamide as porogens and azobisisobutyronitrile as initiator. N-Ethylbutylamine was used to modify the chromatographic surface of the monolith from neutral to cationic. Monolithic columns were termed as multipurpose or multimode columns because they showed mixed modes of separation mechanisms under different conditions. Anion-exchange separation ability in the liquid chromatography (LC) mode can be determined by the cationic chromatographic surface of the monolith. At acidic pH and high voltage across the column, the monolithic stationary phase provided conditions for predominantly capillary electrophoretic migration of peptides. At basic pH and electric field across the column, enhanced chromatographic retention of peptides on monolithic capillary column made CEC mechanisms of migration responsible for separation. The role of pressure, ionic strength, pH, and organic content of the mobile phase on chromatographic performance was investigated. High efficiencies (exceeding 300 000 plates/m) of the monolithic columns for peptide separations are shown using volatile and nonvolatile, acidic and basic buffers. Good reproducibility and robustness of isocratic and gradient elution pressure-assisted CEC/CE separations were achieved for both UV and ESI-MS detection. Manipulation of the electric field and gradient conditions allowed high-throughput analysis of complex peptide mixtures. A simple design of sheathless electrospray emitter provided effective and robust low dead volume interfacing of monolithic multimode columns with ESI-MS. Gradient elution pressure-assisted mixed-mode separation CE/CEC-ESI-MS mass fingerprinting and data-dependent pCE/pCEC-ESI-MS/MS analysis of a bovine serum albumin (BSA) tryptic digest in less than 5 min yielding high sequence coverage (73%) demonstrated the potential of the method.

Electrophoresis, Capillary↗

Management of localized thoracic neuroblastoma.

Thirteen children with localized (Evans stage I or II) thoracic primary neuroblastoma were divided into two groups according to the type of therapy administered, in order to compare the therapeutic efficacy and morbidity of excisional surgery followed by either irradiation alone or irradiation plus chemotherapy (group A) with similar surgery alone (group B). Group A consisted of 6 children (mean age 1 year, 2 months). Complete surgical excision was accomplished in 2 patients, while 4 had microscopic residual. All 6 patients are free of disease at 26--76 months (mean 47 months), including 2 who had recurrent tumor and received additional therapy. Two have developed congestive heart failure and one severe scoliosis secondary to irradiation. Of the 7 children in group B (mean age 2 years, 2 months), 3 had microscopic residual tumor and 2 had adjacent lymph node involvement. After 12--47 months (mean 23 months), no recurrence or surgery-related morbidity has been observed. From these limited data it appears that surgery alone may provide adequate therapy for localized thoracic neuroblastoma and obviate the morbidity associated with multimodal therapy.

Child, Preschool↗

Management of early-stage cervical carcinoma by modified (Type II) radical hysterectomy.

OBJECTIVE: . Surgical management of cervical carcinoma by radical hysterectomy has been proven a highly effective method in treating early-stage disease. The purpose of this study was to evaluate the efficacy and safety of modified (Type II) radical hysterectomy for the treatment of early-stage (I-IIA) cervical carcinoma. METHODS: A retrospective analysis of data on 435 patients with cervical carcinoma who were managed by modified radical hysterectomy was performed. In 145 cases a multimodal approach was used due to the presence of one or more risk factors such as lymph node metastasis, CLS involvement, bulky tumor, and exocervical extension of disease. Preoperative irradiation was offered to 62 patients, whereas adjuvant irradiation was offered to 101 patients. RESULTS: The mean age of the patients was 42.5 years. The majority of the patients had squamous cell cancer (81.6%). The patients were clinically staged as IA (3.2%), IB (86.7%), and IIA (10.1%). Positive pelvic lymph nodes were noted in 65 patients (14.9%). Operative morbidity was minimal, whereas adjuvant radiation treatment had no impact on the disease but caused genitourinary morbidity in terms of ureteral stricture and postoperative bladder dysfunction (P < 0.001). The overall 5-year survival was 88.7%. The most significant predictors related to 5-year survival were nodal metastasis (P < 0.001), adenomatous histology (P < 0.001), lesion size (P < 0.001), and CLS involvement (P = 0.004). Adjuvant radiation resulted in better local pelvic control of the disease. CONCLUSION: The results of our study support the concept that less radical procedures could be effectively applied to early-stage cervical carcinoma 4 cm or smaller with optimal surgical margins.

Adenocarcinoma↗

If cystectomy is insufficient, what is an urologist to do?

Tumor free survival after radical cystectomy is stage dependent. In addition, other features such as the presence of angioinvasion or micropapillary histology also indicate a poor outcome. Failures of definitive therapy by radical cystectomy occur most frequently at distant sites and appear to result from occult micrometastases present at the time of surgery. These clinical data strongly suggest that radical cystectomy provides insufficient treatment for a group of patients at high risk for tumor recurrence. Multimodal therapy (chemotherapy and surgery) seems to improve outcome in such patients, whether given in a neoadjuvant or adjuvant mode. This increased probability of improved outcome with multimodal therapy, however, is accompanied by an almost certain risk of increased toxicity. The neoadjuvant strategy can deliver systemic chemotherapy more reliably and may permit bladder salvage, but adjuvant therapy permits patient selection based on pathology results. The most critical issue in multimodal therapy is patient selection. The choice of neoadjuvant or adjuvant therapy will depend on clinical circumstances, resources, and patient and physician preferences.

Chemotherapy, Adjuvant↗

A model for antagonistic pleiotropic gene action for mortality and advanced age.

Association or linkage studies involving control and long-lived populations provide information on genes that influence longevity. However, the relationship between allele-specific differences in survival and the genetic structure of aging cohorts remains unclear. We model a heterogeneous cohort comprising several genotypes differing in age-specific mortality. In its most general form, without any specific assumption regarding the shape of mortality curves, the model permits derivation of a fundamental property underlying abrupt age-related changes in the composition of a cohort. The model is applied to sex-specific survival curves taken from period life tables, and Gompertz-Makeham mortality coefficients are calculated for the French population. Then, adjustments are performed under Gompertz-Makeham mortality functions for three genotypes composing a heterogeneous cohort, under the constraint of fitting the resultant mortality to the real French population mortality obtained from life tables. Multimodal curves and divergence after the 8th decade appear as recurrent features of the frequency trajectories. Finally, a fit to data previously obtained at the angiotensin-converting-enzyme locus is realized, explaining what had seemed to be paradoxical results-namely, that the frequency of a genotype known as a cardiovascular risk factor was increased in centenarians. Our results help explain the well-documented departure from Gompertz-Makeham mortality kinetics at older ages. The implications of our model are discussed in the context of known genetic effects on human longevity and age-related pathologies. Since antagonistic pleiotropy between early and late survival emerges as a general rule, extrapolating the effects measured for a gene in a particular age class to other ages could be misleading.

Aging↗

Knockdown of the cytoprotective chaperone, clusterin, chemosensitizes human breast cancer cells both in vitro and in vivo.

Clusterin is a stress-associated cytoprotective chaperone up-regulated by various apoptotic triggers in many cancers and confers treatment resistance when overexpressed. The objectives of this study were to evaluate clusterin expression levels in human breast cancer and to determine whether antisense oligonucleotides or double-stranded small interfering RNAs (siRNA) targeting the clusterin gene enhance apoptosis induced by paclitaxel. Clusterin immunostaining was evaluated in a tissue microarray of 379 spotted breast cancers. The effect of hormone withdrawal, paclitaxel treatment, clusterin antisense oligonucleotide (OGX-011), and siRNA treatments on clusterin expression was examined in MCF-7 and MDA-MB-231 cells. Northern, quantitative real-time PCR, and Western analyses were used to measure change in clusterin mRNA and protein levels. The effect of OGX-011 or siRNA clusterin treatment on chemosensitivity to paclitaxel was done in both cell lines in vitro, whereas the ability of OGX-011 to chemosensitize in vivo was evaluated in athymic mice bearing MCF-7 tumors. Clusterin was expressed in 62.5% of tumors within the tissue microarray. Clusterin expression increased after estrogen withdrawal and paclitaxel treatment in vitro in MCF-7 cells. OGX-011 or siRNA clusterin decreased clusterin levels by >90% in a dose-dependent, sequence-specific manner and significantly enhanced chemosensitivity to paclitaxel in vitro. When combined, OGX-011 or siRNA clusterin reduced the IC50 by 2-log compared with paclitaxel alone. In vivo administration of OGX-011 enhanced the effects of paclitaxel to significantly delay MCF-7 tumor growth. These data identify clusterin as a valid therapeutic target and provides preclinical proof-of-principle to test OGX-011 in multimodality therapies for breast cancer.

Adult↗

The effect of gestational age at birth on somatosensory-evoked potentials performed at term.

Multimodality-evoked potentials are widely used in newborns to assess the maturation and integrity of the sensory pathways. Reliable normative data are needed to maximize the utility of this technique as a diagnostic and research tool. Several electrophysiologic studies on the maturational changes of the auditory brain-stem response have demonstrated that latency measurements decrease as a function of increasing conceptional age. However, maturational studies of the somatosensory-evoked potential, particularly in low-risk premature infants, are limited. The existing evoked potential literature in healthy newborns proposes that maturation of the central nervous system occurs at a predictable rate, irrespective of a given gestational age at birth. Behavioral studies of premature infants suggest that neurologic development may be altered by early extrauterine exposure. The purpose of this study was to determine whether brain-stem auditory- or somatosensory-evoked potential conduction times were comparable in premature and full-term infants matched for conceptional age. The results of this study suggest that myelination is determined by conceptional age, independent of premature birth.

Brain Stem↗

Progressive prosopagnosia: clinical and neuroimaging results.

The authors report the longitudinal case study of a patient with the right temporal variant of frontotemporal lobar degeneration. His deficit, initially limited to visuoperceptual disturbances, progressed 2 years later to a severe semantic breakdown. Neuroimaging data indicate that the underlying degenerative process, initially confined to unimodal visual associative cortices, progressed along the ventral pathways to multimodal areas in charge of integrating knowledge from various modalities (the anterior temporal lobes).

Aged↗

Current chemotherapy options for thymic epithelial neoplasms.

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.

Antineoplastic Agents↗