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Surgery, radio- and chemotherapy for multimodal treatment of rectal cancer.

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. The addition of RT to adjuvant CT reduces local relapses without significant impact on survival (NSABP R-02). Vice versa, the addition of CT to RT or an improved CT in the RCT-concept prolongs survival. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 9 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT reduced local relapse rates in addition to total mesorectal excision (TME) but did not extend survival. The preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. Phase III data justifying its routine use in all UICC II + III stages are not yet available. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Preoperative RCT (or RT) may evolve as standard, if the patient selection is improved and postoperative morbidity and long term toxicity reduced. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT at the same indications. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality in adjunction to surgery. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT. In the future, multimodal treatment of rectal cancer might be more effective, if individualized according to prognostic factors.

Chemotherapy, Adjuvant↗

The assessment of attention: I. Standardization and reliability of a behavior-based measure.

Data are presented on standardization and reliability of a behavior-based measure of attention and self-control. This computerized test system administers a series of continuous performance tests, as well as measures of response inhibition. The practicality and sturdiness of this approach have allowed for the development of normative data based on the protocols of 1266 children between 4 and 16 years of age. Test-retest reliability coefficients were high after short intervals (less than 45 days) and 1 year. Originally developed for use in the assessment of children referred for ADD/Hyperactivity, this system has been applied to the evaluation of children with other disorders, as well as to adolescents and adults. Findings are discussed in terms of multimodal assessment, computerization of psychological tests, and the need for cautious standardization.

Adolescent↗

Changes of tibia bone properties after spinal cord injury: effects of early intervention.

OBJECTIVE: To evaluate the effectiveness of an early intervention program for attenuating bone mineral density loss after acute spinal cord injury (SCI) and to estimate the usefulness of a multimodality approach in diagnosing osteoporosis in SCI. DESIGN: A single-case, experimental, multiple-baseline design. SETTING: An SCI center in a university hospital. METHODS: Early loading intervention with weight-bearing by standing and treadmill walking. PATIENTS: Nineteen patients with acute SCI. OUTCOME MEASURES: (1) Bone density by peripheral computed tomography and (2) flexural wave propagation velocity with a biomechanical testing method. RESULTS: Analysis of the bone density data revealed a marked decrease of trabecular bone in the nonintervention subjects, whereas early mobilized subjects showed no or insignificant loss of trabecular bone. A significant change was observed in 3 of 10 subjects for maximal and minimal area moment of inertia. Measurements in 19 subjects 5 weeks postinjury revealed a significant correlation between the calculated bending stiffness of the tibia and the maximal and minimal area moment of inertia, respectively. CONCLUSION: A controlled, single-case, experimental design can contribute to an efficient tracing of the natural history of bone mineral density and can provide relevant information concerning the efficacy of early loading intervention in SCI. The combination of bone density and structural analysis could, in the long term, provide improved fracture risk prediction in patients with SCI and a refined understanding of the bone remodeling processes during initial immobilization after injury.

Adult↗

Registration revisited.

Image registration is important for numerous imaging applications such as three-dimensional reconstruction, multimodality correlations, image averaging and subtraction. Methods used for image registration are based upon either the shape and form of the image pairs or their densitometric relationships. This paper describes the algorithms used for five different registration methods; frequency domain cross-correlation, spatial domain cross-correlation, principal axes/center of mass, fiducials and manual. These methods were compared in terms of their accuracy, efficiency and application with several different data types including different species and modalities. The underlying mathematical bases for each also are presented and compared. The results of the comparisons showed that image quality influenced the behavior of all methods. Images of the blockface provide an excellent reference for subsequent registration. These results also suggest that the statistical performance of various methods is not a reliable metric when distant and different images are registered. Visual comparisons by image overlap and pixel differencing illustrated that some methods are more prone to rotational error than others, especially when repeated pairwise registrations were computed along the rostral/caudal axis.

Algorithms↗

A model for transits in dynamic response theory.

The first goal of vibration-transit (V-T) theory was to construct a tractable approximate Hamiltonian from which the equilibrium thermodynamic properties of monatomic liquids can be calculated. The Hamiltonian for vibrations in an infinitely extended harmonic random valley, together with the universal multiplicity of such valleys, gives an accurate first-principles account of the measured thermodynamic properties of the elemental liquids at melt. In the present paper, V-T theory is extended to nonequilibrium properties, through an application to the dynamic structure factor S(q,omega). It was previously shown that the vibrational contribution alone accurately accounts for the Brillouin peak dispersion curve for liquid sodium, as compared both with molecular-dynamics (MD) calculations and inelastic x-ray scattering data. Here it is argued that the major effects of transits will be to disrupt correlations within the normal-mode vibrational motion and to provide an additional source of inelastic scattering. We construct a parametrized model for these effects and show that it is capable of fitting MD results for S(q,omega) in liquid sodium. A small discrepancy between model and MD at large q is attributed to multimode vibrational scattering. In comparison, mode coupling theory formulates S(q,omega) in terms of processes through which density fluctuations decay. While mode coupling theory is also capable of modeling S(q,omega) very well, V-T theory is the more universal since it expresses all statistical averages, thermodynamic functions, and time correlation functions alike, in terms of the same motional constituents, vibrations and transits.

Journal Article↗

Hemodynamic monitoring in the care of the critically ill neuroscience patient.

Hemodynamic monitoring in the care of the critically ill neuroscience patient provides information that assists the clinician in minimizing secondary neuronal injury. Whereas no technology replaces the critical care nurse's physical assessment, hemodynamic and neurological monitoring provides additional data beyond what is possible with the clinical examination alone. If neurological technology, such as intracranial pressure monitoring, is not available, hemodynamic monitoring along with the neurological examination provides limited but useful information essential to minimizing secondary neuronal injury. The use of hemodynamic monitoring in critically ill neuroscience patients is best exemplified in the management of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Although improved outcomes have not been scientifically substantiated, multimodality monitoring of intracranial dynamics and systemic hemodynamics and manipulation of these parameters during hypertensive hypervolemic hemodilution therapy may lessen the incidence of cerebral infarction secondary to vasospasm. Monitoring systemic hemodynamics and intracranial dynamics simultaneously assists in prevention, prompt recognition, and effective treatment of neurological deterioration.

Brain Ischemia↗

[Malignancy: treatment and prognosis of gastrointestinal and pancreatic endocrine neoplasia: retrospective study of a series of 16 cases].

The aim of this study was to review our experience with endocrine tumours of the gastrointestinal tract and pancreas (ETGIP). Between February 1991 and March 2000, sixteen patients with ETGIP were operated on at our institution. Of these patients we reviewed preoperative symptoms, diagnostic techniques (ultrasound, CT, MRI, radiolabelled octreotide scintigraphy, angiography, immunohistochemical study), treatment (surgical operation, neoadjuvant and adjuvant chemotherapy, and radiometabolic therapy) and survival. Nine patients (56%) had a carcinoid tumour, three (19%) an unspecified endocrine tumour, and four (25%) an endocrine tumour associated with a non-endocrine neoplasm. Only five patients (31%) had a preoperative diagnosis of endocrine tumour. Eight patients (50%) had metastatic disease at the time of the operation. All patients without preoperative metastasis (eight patients, 50%) are still alive without recurrent disease, with a mean postoperative survival of 36 months (12-60 months). Of eight patients with metastatic disease, six (75%) died after a mean of 20.5 months (3-60 months) and two (25%) are still alive with the disease after 3 and 6 months, respectively. These data show that presence of metastasis strongly influence survival. Furthermore, survival of patients with metastatic disease seems to be longer as compared to other gastrointestinal tract malignancies. ETGIP are more common and aggressive than previously believed and, therefore, early diagnosis is crucial for cure. Nowadays, however, new diagnostic tools such as radiolabelled octreotide scintigraphy are available for diagnosis and postoperative follow-up. The optimal treatment for ETGIP is a multimodal approach with surgical operation, chemoradiation, radiometabolic, and genetic therapies.

Adult↗

[Use of analgesics with peripheral action in the system of complex protection of the patient from operative trauma].

Obtained for many years experience of perioperative using of analgesics with peripheral effect is summarized. The special scientific analysis was carried out in 274 patients who got different analgesics with peripheral action (aspisol, baralgin, ketoprofen, ketorolak, contrikal) at different stages of preoperative period in combination with opioid. The control group included 30 patients who got monoanalgesia by promedol after abdominal operations. The dynamics of pain, hemodynamics, respiration, gas-exchange, blood coagulation and rheology indices as well as side effects of analgesics were estimated. The best results have been obtained in cases with preventive therapy by non-steroid anti-inflammatory drug 1 hour before beginning of operation and subsequent therapy continuation after operation. Under such conditions complete analgesia after operation with moderate traumaticity is achieved in combination with low dose of small opioid (tramal) in daily dose of 235 mg. The introducing of non-steroid anti-inflammatory drugs was not followed by any hemorrhagic complication, and as was evident from electrocoalugraphic data improved blood rheology. After severe traumatic abdominal or thoracal operations non-steroid anti-inflammatory drugs are used in combination with other potent analgesic with peripheral action--cortical and opioid buprenofine in minimal dose of 0.35 mg/day with good analgesic effect. To prevent the central sensitization during general anesthesia ketamine in microdose 0.5-1.0 mg/kg*hour is always used. The conclusion is made on the important role of multimodal preventive and continuous perioperative antinociceptive protection.

Analgesia↗

[Plasmapheresis in the treatment of rapidly progressing glomerulonephritis].

The authors are of the opinion that plasmapheresis (PP) combined with immunosuppressant therapy is an effective and a relatively safe method for the treatment of rapidly progressing glomerulonephritis (RPGN). Introduction of PP in multimodality treatment of RPGN made it possible to arrest rapidly progressing renal failure in all 6 treated patients. After PP treatment was over, renal function was recovered completely in 3 patients. One patient manifested the retention of renal failure of medium degree while rare hemodialysis sessions permitted one to control water-electrolyte disorders. In two patients the discontinuation of PP treatment resulted in the progress of renal failure. The data obtained do not make it possible to relate the improvement of renal function exclusively to the action of PP, since all the patients received immunosuppressants. Nevertheless, in 2 cases, the improvement could be attributed to PP, for its discontinuation in these patients (without any changes in the remaining treatment) brought about again the progress of renal failure.

Adult↗

Limiting excessive postoperative blood transfusion after cardiac procedures. A review.

Analysis of blood product use after cardiac operations reveals that a few patients (< or = 20%) consume the majority of blood products (> 80%). The risk factors that predispose a minority of patients to excessive blood use include patient-related factors, transfusion practices, drug-related causes, and procedure-related factors. Multivariate studies suggest that patient age and red blood cell volume are independent patient-related variables that predict excessive blood product transfusion after cardiac procedures. Other factors include preoperative aspirin ingestion, type of operation, over- or underutilization of heparin during cardiopulmonary bypass, failure to correct hypothermia after cardiopulmonary bypass, and physician overtransfusion. A survey of the currently available blood conservation techniques reveals 5 that stand out as reliable methods: 1) high-dose aprotinin therapy, 2) preoperative erythropoietin therapy when time permits adequate dosage before operation, 3) hemodilution by harvest of whole blood immediately before cardiopulmonary bypass, 4) autologous predonation of blood, and 5) salvage of oxygenator blood after cardiopulmonary bypass. Other methods, such as the use of epsilon-aminocaproic acid or desmopressin, cell saving devices, reinfusion of shed mediastinal blood, and hemofiltration have been reported to be less reliable and may even be harmful in some high-risk patients. Consideration of the available data allows formulation of a 4-pronged plan for limiting excessive blood transfusion after surgery: 1) recognize the causes of excessive transfusion, including the importance of red blood cell volume, type of procedure being performed, preoperative aspirin ingestion, etc.; 2) establish a quality management program, including a survey of transfusion practices that emphasizes physician education and availability of real-time laboratory testing to guide transfusion therapy; 3) adopt a multimodal approach using institution-proven techniques; and 4) continually reassess blood product use and analyze the cost-benefits of blood conservation interventions.

Aspirin↗

[Prognostic factors in primary gastric non-Hodgkin's lymphoma--results of uni- and multivariate analysis].

Retrospectively analyzed data of 41 patients with primary gastric non-Hodgkin lymphoma which were all treated by gastric resection are presented with regard to their histopathologic and clinical findings. 87% of the patients were distributed on stage EI and EII (51% high-grade and 49% low-grade lymphoma). R0 resection was achieved in 80% of our cases and in 27% of the cases gastric resection was part of a multimodal therapy. The median follow up of the living patients was 42 months, the overall 5-year survival rate 74%. Tumor stage, extent of surgical resection, histologic grade, tumor site, R0-resection and tumor size showed a significant prognostic influence on survival. The question whether R0 resectable cases benefit from an adjuvant therapy must be answered by further randomized studies.

Adult↗

[FastTrack approach to major colorectal surgery].

Intensive rehabilitation programs after major abdominal, thoracic and vascular surgery have been published over the last few years, showing early recovery, fewer complications and a quicker discharge. The aim of the study was to evaluate the feasibility and efficacy of a multimodal intensive rehabilitation program (FastTrack) after major colorectal surgery, according to the experience of Dr. H. Kehlet of Hvidovre University Hospital, Copenhagen. The study design was of the prospective, randomized, controlled type. Forty patients undergoing elective colonic surgery were randomly selected and assigned to two groups well matched for age, weight, ASA and type of resection. The FastTrack group underwent a multimodal rehabilitation program with epidural analgesia, short laparotomy, early feeding and mobilisation. The control group had the usual postoperative treatment with a pain control program. The FastTrack group exhibited a shorter need for assisted ventilation, a lower sedation level and lower opioid consumption over the first 24 hours. We also observed a statistically significant earlier onset of peristalsis (0.5 vs 2.7 days), gastrointestinal function (defecation) (2.8 vs 5.8 days), regular feeding (3.1 vs 7.2 days) and autonomous ambulation (3.3 vs 6.9). The multimodal rehabilitation approach to colon surgery permits an earlier postoperative recovery, better postoperative performance and quicker functional autonomy. These results may have important implications for the management of patients after major colorectal surgery.

Aged↗

Real-time multimodal medical image processing: a dynamic volume-rendering application.

In the present research, a system for medical image processing has been proposed, which allows multimodal dynamic three-dimensional (3-D) visualization interactively and in real time. The system has been conceived to support medical specialists in the diagnosis of moving organs, such as the heart during the cardiac cycle, allowing them to compare information on perfusion/contraction match as a basis for diagnosis of important cardiovascular diseases. The 3-D volume-rendering algorithm runs on a SIMD machine because of the great amount of data to be manipulated by always using the same operations. One of the features of the algorithm is the possibility to change, interactively, image processing and visualization parameters at any step, and to perform simple and effective image manipulations. Performance studies have demonstrated a very high global efficiency in practical situations by using typical data-volume dimensions. The system has been tested in the medical environment, by using magnetic resonance (MR) and single-photon emission-computed tomographic (SPECT) images.

Algorithms↗

Radiotherapy in the treatment of uterine sarcomas. A retrospective analysis of 54 cases.

BACKGROUND: In the general population, uterine sarcoma (US) is an uncommon tumor, which accounts for approximately 1-3% of all uterine neoplasms. Its biological behavior is characterized by hematogenous metastases and local recurrent growth including the pelvis and peritoneal cavity. In the management of US, surgery is the primary form of treatment. Up to now the role of adjuvant radiotherapy has not been clearly established. PATIENTS AND METHODS: We report about 54 patients with US treated from 1954 to 1994 by surgical resection alone (22) or a combination of surgery and irradiation (32) and evaluate the influence of histology, stage and different treatment options on survival. RESULTS AND CONCLUSIONS: Our data indicate an increased disease-free survival for patients treated with adjuvant radiotherapy, especially if poor prognostic factors are present (advanced tumor stage, histopathological grade II or III of leiomyosarcoma and mixed mesodermal sarcoma). Postoperative irradiation using doses between 50 and 60 Gy is recommended, in selected cases brachytherapy should be added. Prospective multicentric trials including a statistically evaluable number of patients are necessary to further clarify the role of multimodality treatment programs for US.

Disease-Free Survival↗

MYCN deregulation as a potential target for novel therapies in rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Treatment requires a multimodality approach combining chemotherapy with surgery and radiotherapy. Although overall outcomes have improved considerably, the outlook for patients with high-risk disease, particularly the alveolar subtype, remains bleak and there is a clear need for new chemotherapeutic strategies. This review focuses on the possibilities for interventions targeting myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN). The importance of aberrant expression of this oncogene is well established in neuroblastoma and recent data indicate that MYCN deregulation also occurs in up to a quarter of alveolar subtype cases. A range of possible approaches to target MYCN is discussed, including nucleic acid-based and immunotherapy strategies.

Antineoplastic Agents↗

Present and potential future issues in glioblastoma treatment.

The treatment of glioblastomas requires a multidisciplinary approach that takes the presently incurable nature of the disease into consideration. Treatments are multimodal and include surgery, radiotherapy and chemotherapy. Current recommendations are that patients with glioblastomas should undergo maximum surgical resection, followed by concurrent radiation and chemotherapy with the novel alkylating drug temozolomide. This is then to be followed by additional adjuvant temozolomide for a period of up to 6 months. Major advances in surgical and imaging technologies used to treat glioblastoma patients are described. These technologies include magnetic resonance imaging and metabolic data that are helpful in the diagnosis and guiding of surgical resection. However, glioblastomas almost invariably recur near their initial sites. Disease progression usually occurs within 6 months and leads rapidly to death. A number of signaling pathways can be activated constitutively in migrating glioma cells, thus rendering these cells resistant to proapoptotic insults, such as conventional chemotherapies. Therefore, the molecular and cellular therapies and local drug delivery that could be used to complement conventional treatments are described, and some of the currently ongoing clinical trials are reviewed, with respect to these new approaches.

Antineoplastic Combined Chemotherapy Protocols↗

Analysis of one hundred and twenty five patients with primary liver cancer surviving more than five years.

During the period of 1958-1986, a series of 125 patients with pathologically proven hepatocellular carcinoma (HCC) surviving more than 5 years was collected in authors' institute. Thirty seven of them survived more than 10 years, the longest being 30 years. Of the entire series, 55.2% of patients was discovered by screening, 48.0% of patients was subclinical HCC, 80.0% of patients had solitary tumor, and 53.6% of patients had tumor size smaller than 5 cm. Pathological findings revealed that 90.2% of tumor was grade I and II (Edmondson grading) and 81.6% of patients associated with cirrhosis. The serum HBsAg was positive in 63% and anti-HBc in 80% of the patients who had checked the HBV markers. Of the 125 patients, 108 patients received resection, 67 patients were small HCC resection, 41 patients were non-small HCC resection, re-resection for subclinical recurrence or solitary lung metastasis was done in 26 patients with resection. Limited resection amounted to 54.6% of patients with resection. Of the 125 patients, 17 patients received palliative surgery other than resection, including hepatic artery ligation, cannulation, or their combination, etc. Eight out of the 17 patients received second stage resection due to marked shrinkage of tumor. It is concluded that early resection remained the major approach to get a long-term survivor, re-resection for subclinical recurrence is also of proved merit. Resection of huge tumor is still useful but less effective. Cyto-reduction and sequential resection is a new trend. Primary liver cancer (PLC) has long been recognized as incurable malignancy with extremely low 5-year survival rate. According to the cancer statistics in the United States, the relative 5-year survival rates for patients with PLC was 2% in 1960-1963, 3% in 1970-1973, 4% in 1974-1976, 3% in 1977-1980 and 5% in 1981-1986. Patients with PLC survived more than 5 years were rarely reported in the literature. In 1971, Curutchet collected worldwide data from 45 authors covering the period for 65 years (1905-1970), only 45 patients with PLC were found to be 5-year survivors. Thanks to the progress in tumor markers, particularly alpha fetoprotin (AFP) and new localization measurements, diagnosis and treatment are possible in subclinical stage. Based on combined strategies to the treatment of PLC including resection of small liver cancer, re-resection of subclinical recurrence after curative resection, multimodality treatment, and sequential resection after shrinkage of tumor, the 5-year survival of PLC has gradually increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Three-dimensional statistical analysis of sulcal variability in the human brain.

Morphometric variance of the human brain is qualitatively observable in surface features of the cortex. Statistical analysis of sulcal geometry will facilitate multisubject atlasing, neurosurgical studies, and multimodality brain mapping applications. This investigation describes the variability in location and geometry of five sulci surveyed in each hemisphere of six postmortem human brains placed within the Talairach stereotaxic grid. The sulci were modeled as complex internal surfaces in the brain. Heterogeneous profiles of three-dimensional (3D) variation were quantified locally within individual sulci. Whole human heads, sectioned at 50 micrometer, were digitally photographed and high-resolution 3D data volumes were reconstructed. The parieto-occipital sulcus, the anterior and posterior rami of the calcarine sulcus, the cingulate and marginal sulci, and the supracallosal sulcus were delineated manually on sagittally resampled sections. Sulcal outlines were reparameterized for surface comparisons. Statistics of 3D variation for arbitrary points on each surface were calculated locally from the standardized individual data. Additional measures of surface area, extent in three dimensions, surface curvature, and fractal dimension were used to characterize variations in sulcal geometry. Paralimbic sulci exhibited a greater degree of anterior-posterior variability than vertical variability. Occipital sulci displayed the reverse trend. Both trends were consistent with developmental growth patterns. Points on the occipital sulci displayed a profile of variability highly correlated with their 3D distance from the posterior commissure. Surface curvature was greater for the arched paralimbic sulci than for those bounding occipital gyri in each hemisphere. On the other hand, fractal dimension measures were remarkably similar for all sulci examined, and no significant hemispheric asymmetries were found for any of the selected spatial and geometric parameters. Implications of cortical morphometric variability for multisubject comparisons and brain mapping applications are discussed.

Aged↗