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Better Selection (good + selection)
Selected AbstractsTumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers.HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2007A review Abstract Background. Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short- and long-term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. Methods. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia-related markers. Results. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia-related markers include hypoxia inducible factor (HIF)-1,, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. Conclusions: A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Barrett's oesophagus,a pathologist's viewHISTOPATHOLOGY, Issue 1 2007J-F Fléjou Barrett's oesophagus, a precancerous condition for oesophageal adenocarcinoma, detected on endoscopy and confirmed on histology, shows intestinal metaplasia of the lower oesophagus. The significance of microscopic foci of intestinal metaplasia at the gastro,oesophageal junction, corresponding either to so-called ,ultrashort' segment Barrett's oesophagus, or to carditis with intestinal metaplasia, is still a matter of debate. The surveillance of patients with Barrett's oesophagus is still based on systematic biopsy sampling of Barrett's mucosa on endoscopy, looking for dysplasia. Although well-established classifications of dysplasia are now used by most pathologists, there remain numerous problems with this subjective marker (sampling, diagnostic reproducibility, natural history, etc). Therefore, many alternative biomarkers have been proposed, but only DNA aneuploidy, proliferation markers and p53 loss of heterozygosity/overexpression have been shown to be of some use at the present time. Some endoscopic improvements already allow a better selection of biopsies, and it may be that in future new technologies will allow ,virtual biopsies'. On the other hand, the role of pathologists now extends to the evaluation of new therapeutic modalities of early neoplastic lesions in Barrett's oesophagus, especially endoscopic mucosal resection. [source] Present and future therapeutic strategies for idiopathic oligozoospermiaINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2000Dimitrios A. Adamopoulos The effectiveness of medical treatment for idiopathic oligozoospermia (IO) has been at best doubtful until now and a logical consequence of this unsatisfactory situation has been the partial displacement of this approach by assisted reproduction techniques. This state of affairs has resulted from insufficient investigation, inappropriately designed clinical trials and consistent disregard for the principles of evidence-based medicine. Protocol-related shortcomings and wrong interpretation of the data available have also been some of the all too frequent problems encountered in this therapeutic approach. In this rather misty situation, it appears that, of the therapeutic agents used so far, follicle stimulating hormone (FSH) (mainly FSH-secretagogues) may exert some beneficial effects on a number of biological endpoints related to spermatogenesis and sperm maturation. The short and medium term prospects of medical treatment for IO rest mainly with improvement of investigative procedures to a higher degree of sophistication, with emphasis placed on identifying the causes rather than the results of dysfunction so that a better selection of candidates can be made. Moreover, the introduction of prognostic indices for evaluation of the beneficial effects of a therapeutic agent may be of paramount importance. Finally, a better assessment of the preparations available and, possibly, the introduction of new more specific agents may also be an important step forward in this field. This type of large-scale effort should not be left to individual investigators or special centres working independently, but it may come under the auspices of a central regulating agency so that undisputed results from large, multicentre and uniform studies might be obtained, if medical treatment is to remain a good option. In this context, it may also be emphasized that andrology's main task should always be to treat the male with the problem rather than his healthy female partner, whenever this is possible. [source] Bivariate flood frequency analysis: Part 1.JOURNAL OF FLOOD RISK MANAGEMENT, Issue 4 2008Determination of marginals by parametric, nonparametric techniques Abstract In flood frequency analysis, a flood event is mainly characterized by peak flow, volume and duration. These three variables or characteristics of floods are random in nature and mutually correlated. In this article, an effort is made to find out appropriate marginal distribution of the flood characteristics considering a set of parametric and nonparametric distributions, and further mathematically model the correlated nature among them. A set of parametric distribution functions and nonparametric methods based on kernel density estimation and orthonormal series are used to determine the marginal distribution functions for peak flow, volume and duration. In conventional methods of flood frequency analysis, the marginal distribution functions of peak flow, volume and duration are assumed to follow some specific parametric distribution function. The present work performs a better selection of marginal distribution functions for flood characteristics as both parametric and nonparametric estimation procedures are extensively followed. The methodology is demonstrated with 70-year stream flow data of Red River at Grand Forks of North Dakota, USA. [source] Evolution of liver transplantation in Europe: Report of the European Liver Transplant RegistryLIVER TRANSPLANTATION, Issue 12 2003René Adam MD The European Liver Transplant Registry (ELTR) currently allows for the analysis of 44,286 liver transplantations (LTs) performed on 39,196 patients in a 13-year period. After an exponential increase, the number of LTs is plateauing due to a lack of organs. To cope with this, alternatives to cadaveric LT, such as split LT, domino LT, or living-related LT (LRLT) are being used increasingly. They now account for 11% of all procedures. One of the most important findings in the evolution of LT is the considerable improvement of results along time with, for the mean time, a one-year survival of 83%, all indications confounded. The improvement is particularly significant for cancers. This improvement is mainly represented by hepatocellular carcinoma, with a gain of 17% for 5-year survival rate from 1990 to 2000. Increasingly, older donors are used to augment the donor pool and older recipients are transplanted due to improved results and a better selection of patients. More than two thirds of deaths and three quarters of retransplantations occurred within the first year of transplantation. Retransplantation is associated with much less optimal results than first LT. One of the prominent features of recent years is the development of LRLT. LRLT is now performed by almost half of the European centers. As with split LT or domino LT, LRLT aims to provide more patients to be transplanted. Special attention is paid to reducing the risk for the donor, which is now estimated to be 0.5% mortality and 21% postoperative morbidity. [source] Neoadjuvant chemotherapy: a new criterion for selection of candidate patients for surgery of low tumour burden metastases from malignant melanoma?BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2010T. Jouary Summary Background, Surgery of limited metastatic lesions from malignant melanoma can achieve long-term remission and better survival than chemotherapy. Existing criteria for selection of candidate patients for this surgery do not seem sufficient to avoid useless excisions. Objectives, To test use of neoadjuvant chemotherapy as a new criterion in this setting. Methods, All patients who underwent thoracic surgery for one or two lung metastases from melanoma during 1999,2007 were included in the study. Demographic and medical data were collected and analysed. Several possible prognostic factors were evaluated based on the overall survival curves. Results, Thirteen patients were included in this retrospective study. All but two patients had no evidence of disease after surgery. Ten patients received neoadjuvant chemotherapy. Six responded (absence of progression) and four had progressive disease. Response to chemotherapy and no evidence of disease after surgery were predictive of long-term survival. Conclusions, Neoadjuvant chemotherapy can be considered as a new criterion for better selection of candidate patients for lung metastasis surgical resection. This would also avoid useless surgical procedures in rapidly progressive disease and give information on the chemosensibility of the metastatic disease. This study needs further confirmation, particularly with chemotherapy regimens that have demonstrated better objective responses. [source] Prognostic factors in adult acute lymphoblastic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2010Jacob M. Rowe Summary Treatment of acute lymphoblastic leukaemia (ALL) in adults presents a formidable challenge. While overall results have improved over the past 3 decades, the long-term survival for patients aged less than 60 years is only in the range of 30,40% and is 10,15% if between 60 and 70 years and <5% for those over 70 years. The historic lack of clear-cut biological prognostic factors has led to over- or under-treatment of some patients. Response to initial therapy is an important prognosticator of outcome based on disease biology, as well as pharmacogenetics, which include the patient's response to drugs given. The more widespread availability of allogeneic transplantation and reduced-intensity regimens for older patients have opened up this curative modality to a greater number of patients. Hopefully, those options, as well as novel cytogenetic and molecular markers, will enable a better selection of patients who undergo intensive therapies and finally break the 30,40% cure barrier for adults with ALL. [source] Haemophagocytic lymphohistiocytosis: proposal of a diagnostic algorithm based on perforin expressionBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2002Maurizio Aricò Summary. Haemophagocytic lymphohistiocytosis (HLH) is a rare, fatal disorder of early infancy. Mutations of the PRF1 gene have been identified in a subset of patients. However, the distinction between the different genetically determined and environmental subtypes of the disease remains a major issue to be solved. This may result in delayed or inappropriate application of bone marrow transplantation (BMT). We propose an algorithm that uses a combination of three rapid laboratory tests, i.e. perforin expression by peripheral lymphocytes, assessment of the behaviour of the 2B4 lymphocyte receptor and natural killer (NK) cell activity, to identify the different subgroups of HLH. In 19 patients diagnosed according to current criteria, we tested perforin expression, 2B4 receptor function and NK cell activity. PRF1 mutations were found in all seven patients showing absent perforin expression. In one male with abnormal behaviour of the 2B4 receptor, SH2D1A mutation confirmed the diagnosis of X-linked lymphoproliferative disease. Four patients with normal NK cell activity had evidence of associated infections. Of the seven with impaired NK cell activity, two had a probable genetically determined subtype of HLH and five appeared as sporadic, infection-associated cases. Improving the diagnostic approach may restrict the use of BMT, the only recognized curative treatment, to HLH patients with a documented poor prognosis while patients with milder disorders may be treated less intensively. Our flow chart could also lead to better selection of patients for specific gene analysis. [source] A prospective evaluation of occult disorders in obstructed defecation using the ,iceberg diagram'COLORECTAL DISEASE, Issue 9 2006M. Pescatori Abstract Objective, Surgical treatment of constipation and obstructed defecation (OD) carries frequent recurrences, as OD is an ,iceberg syndrome' characterized by ,underwater rocks' or occult diseases which may affect the outcome of surgery. The aim of this study was to evaluate occult disorders in order to alert the clinician of these and minimize failures. Method, One hundred consecutive constipated patients with OD symptoms, 81 female patients, median age 52 years, underwent perineal examination, proctoscopy, anorectal manometry, and anal/vaginal ultrasound. Anorectal physiology and imaging tests were also carried out when indicated, as well as psychological and urogynaecological consultation. Symptoms were graded using a modified 1,20 constipation score. Both evident (e.g. rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using a novel ,iceberg diagram'. The type of treatment, whether conservative or surgical, was also recorded. Results, Fifty-four (54%) patients had both mucosal prolapse and rectocele. All patients had at least two occult OD-related diseases, 66 patients had at least three: anxiety-depression, anismus and rectal hyposensation were the most frequent (66%, 44% and 33% respectively). The median constipation score was 11 (range 2,20), the median number of ,occult disorders' was 5 (range 2,8). Conservative treatment was carried out in most patients. Surgery was carried out in 14 (14%) patients. Conclusion, The novel ,iceberg diagram' allowed the adequate evaluation of OD-related occult diseases and better selection of patients for treatment. Most were managed conservatively, and only a minority were treated by surgery. [source] | ||||||||||