摘要:

Purpose of reviewThe purpose of this review is to summarize recent advances within the area of genetic polymorphisms with a specific emphasis on renal transplantation, and to discuss the potential clinical applications.Recent findingsDue to recent advances in molecular techniques, there has been an abundance of publications describing genetic variability in molecules relevant to transplant outcome. Many studies are now demonstrating associations between polymorphisms in these candidate genes and outcomes in organ transplantation.SummaryThese studies emphasize the potential role of genetic variability in transplantation, and provide the rationale for large prospective studies to clearly define the potential benefits of genotyping in the risk stratification of transplant recipients.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewHypertension is very common in renal transplant recipients and is a significant risk factor for mortality from cardiovascular diseases and for development of graft dysfunction.Recent findingsRecent guidelines for the treatment of hypertension (Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure VI Report and World Health Organization Guidelines) do not directly address post-transplant hypertension. Specific recommendations for the drug treatment of hypertension in renal allograft recipients have not been given in the Clinical Practice Guidelines of the American Society of Transplantation or those of the European Renal Association.SummaryThe present paper summarizes some important aspects of post-transplant hypertension and discusses potential treatment strategies aimed at reducing blood pressure and thus improving patient and allograft survival.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewPostischaemic acute renal allograft failure is among the main risk factors for reduced transplant survival. Although new immunosuppressive protocols have reduced the number of acute rejections, the incidence of acute renal failure remained unchanged. On the basis of histomorphology it is not possible to predict donor kidneys at risk of subsequent failure. Some factors are associated with failure, but even combinations of these risk factors can not precisely predict the development of acute renal failure. Studies have therefore evaluated the influence of demographic donor and recipient factors on acute renal failure. New biotechnology and data mining tools are currently being used to study and identify the molecular predictors of acute renal failure.Recent findingsRecent studies showed that donor factors contributed to approximately 40% of the variability in early allograft function. Deductive approaches identified some isolated molecular targets, such as adhesion molecules, as risk factors. Explorative analysis of the entire human genome, however, identified several predictive clusters of genes, which can be functionally grouped into categories such as cell death, stress response, cell adhesion, transcription factors, inflammatory response or cell cycle-related genes. Based on this information, preventative strategies using antisense oligonucleotides or antibodies were adopted. Clinical studies identified the use of catecholamines in the organ donor as beneficial. All these efforts aim to reduce renal tubular damage.SummaryA detailed analysis of the molecular events and pathways of renal gene expression in the donor and after reperfusion, together with sophisticated data analysis tools, will provide new insights into the pathophysiology of acute renal failure.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewWith the improved long-term outcome of renal allograft recipients, malignant tumours or cardiovascular disease become increasingly important. Malignant tumours develop in 15-20% of graft recipients after 10 years, and thus contribute substantially to the morbidity and mortality of these patients. In contrast to the general population, skin tumours and lymphoproliferative disorders are the most frequent malignancies in transplant recipients. Malignancies can develop in three ways: de-novo occurrence in the recipient; recurrent malignancy in the recipient; or transmission of malignancy from the donor.Recent findingsThe immunosuppressive strategies after renal transplantation differ with respect to the development of malignancies, with cell-depleting antibodies being the highest risk, whereas newer immunosuppressants such as rapamycin could possess anti-tumour potential. The relationship of chronic viral infections to skin tumours and lymphoproliferative diseases has become clearer during recent years. Concomitantly, experience in the management of such diseases has grown. Furthermore, as older donors are accepted, awareness of the possibility of transferring malignancies from the donor to the recipient must increase.SummaryMalignancies are a major contributor to morbidity and mortality among kidney transplant recipients as such diseases gain importance with longer graft survival. Immunosuppression and chronic viral infections in combination with the transmission of malignant cells from the donor or recurrent malignancies contribute to the increased incidence of cancer. In kidney transplant recipients, screening before and after transplantation and an individualized choice of immunosuppression are thus mandatory.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewWe outline a generic approach to using a nomogram to predict a continuous probability of failure in high-risk patients (rather than putting patients into groups), in order to identify patients whose risk exceeds a cutoff point. We discuss the goals of any staging system, what markers should be included, and models of markers.Recent findingsSelection of high-risk patients for any cancer has traditionally been accomplished by the creation of risk groups, or perhaps clinical stages. Ideally, high-risk patients should be identified as accurately as possible, because of the treatment and psychological implications for the patient. We argue that a continuous multivariable prediction model, such as a nomogram, is the most appropriate and accurate way to select high-risk patients. This type of model predicts outcome more accurately than risk grouping or staging systems. As an example, we use our preoperative prostatic specific antigen recurrence nomogram to identify patients at high risk of biochemical failure, who are in need of an effective neoadjuvant therapy.SummaryIt will follow from our discussion that identification of high-risk patients should follow four simple steps. First, select the endpoint of interest for the trial or the patient. Second, select the method that predicts the endpoint as accurately as possible. Third, determine the cutoff of predicted probability beyond which it makes sense to give the patient experimental therapy. Fourth, offer the novel therapy to the patient whose prediction of the endpoint, using the most accurate prediction method, exceeds the threshold.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe use of adjuvant radiation therapy following prostatectomy is commonplace. The purpose of this review is to summarize completed and ongoing clinical trials and to review recent relevant studies and debates related to this subject.Recent findingsThe routine use of adjuvant radiation therapy remains a controversial topic. Recent retrospective matched-pair analyses support its use in appropriately selected patients with positive margins, extraprostatic extension or seminal vesicle invasion, but interpretation of these and other data vary. Although the 5-year biochemical recurrence rate using adjuvant radiotherapy may be decreased from approximately 40 to 10% in patients with either positive margins or extraprostatic extension, its effect on cause-specific mortality is unclear. Two prospective randomized trials with cumulative enrollment of over 1400 patients have examined the role of adjuvant radiation therapy compared with observation following prostatectomy: one trial was a National Cancer Institute-sponsored Intergroup study coordinated by the Southwest Oncology Group, and the other was from the European Organization for Research and Treatment of Cancer. Currently, the Radiation Therapy Oncology Group is conducting a three-arm trial, with broadened stratification criteria as compared with previous trials. This ongoing trial examines the use of adjuvant radiotherapy with or without adjuvant androgen deprivation following prostatectomy and also androgen deprivation alone in patients at high risk for disease relapse.SummaryIn lieu of data from completed randomized trials, indications for immediate adjuvant radiation therapy following prostatectomy exist and are supported by retrospective data with respect to reducing local and biochemical recurrence rates. However, data demonstrating an overall or cause-specific survival advantage for adjuvant radiotherapy as compared with delayed salvage therapy do not exist.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewWith the advent of prostate-specific antigen, stage migration has resulted in a shift towards early-stage prostate cancer at diagnosis. Although radical prostatectomy and radical radiotherapy can be curative in organ-confined disease, there remains a significant proportion of early-stage patients who go on to develop progressive, incurable disease. This review will highlight developments in the identification of high-risk patients, and summarize the results of investigations of adjuvant chemotherapy in this setting.Recent findingsThe ability to identify patients at high risk of developing progressive disease is improving. Both preoperative and postoperative variables, as well as newer radiographic and molecular tools, can identify at-risk patients who may benefit from adjuvant therapy. Coupled with developments in chemotherapeutic agents for prostate cancer, this provides the rationale for investigating chemotherapy in this setting. Unfortunately, to date, reported trials involving adjuvant chemotherapy in prostate cancer are few, and generally involve small numbers of patients. Some of the studies confirm that certain populations of patients, such as those with node-positive disease, may benefit from systemic therapy. Definitive data, however, will be derived from ongoing randomized trials investigating adjuvant chemotherapy.SummaryAlthough definitive data regarding systemic chemotherapy in adjuvant therapy are scarce, the results of the available studies, and the increasing accuracy in delineating the population at risk, have laid the foundation for future and ongoing studies in this area.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThere are limited effective therapies that would persuade most urologists actively to screen for and treat patients who have developed asymptomatic bone metastases.Recent findingsRecently published trials regarding new treatment options for patients with high-risk metastatic prostate cancer are now available, which describe the utility of the intravenous bisphosphonate zoledronic acid.SummaryProstate cancer is the most common malignancy in men in the United States. Many prostate cancer patients, especially those with aggressive and advanced disease, are at increased risk of developing bone metastases and, subsequently, skeletal-related events. Skeletal-related events may result both from disease and/or treatment of disease, and include bone pain, pathological fractures and spinal cord compressions. Furthermore, bone radiation and surgery to address bone-related pain, prevent pathological fractures and/or spinal cord compression are also considered skeletal-related events. These sequelae of bone metastases are both painful and debilitating, and severely compromise a patient's quality of life.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe number one cause of death in the United States and in most countries around the world is cardiovascular disease. The number one or number two cause of death in prostate cancer patients is also cardiovascular disease. These observations do not serve to belittle the impact of prostate cancer, but are a reminder that the ultimate goal of healthy lifestyle recommendations is to reduce the burden of both of these major causes of death, especially after definitive prostate therapy. Patients need to be encouraged to know their cholesterol levels and other cardiovascular markers including blood pressure, as well as being aware of their prostate-specific antigen values.Recent findingsPatients should not smoke, they should reduce their intake of saturated and trans fats, increase their consumption of a diversity of fruit and vegetables, consume moderate quantities of dietary soy or flaxseed, increase their consumption of fish or fish oils and other ω-3 fatty acids, as well as maintaining a healthy weight, getting at least 30 min/day of physical activity, and lifting weights several times a week. When in doubt it is important for the clinician and patient to realize that what is healthy for the heart is generally found to be healthy for the prostate. Many of these lifestyle changes, when accomplished on a regular basis, may dramatically reduce the risk of overall early mortality. Despite the simplistic and moderate recommendations in this manuscript, research suggests that few individuals are currently following these suggestions.SummaryClinicians need to constantly emphasize these basic changes in order to truly impact the overall health of any patient following definitive prostate therapy.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe number one cause of death in the United States and in most countries around the world is cardiovascular disease. The number one or two cause of death in prostate cancer patients is also cardiovascular disease. These observations do not serve to belittle the impact of prostate cancer, but serve as a reminder that the ultimate goal of dietary supplement recommendations is to reduce the burden of both of these major causes of death, especially after definitive prostate therapy. Several supplements should be discussed with a patient following definitive prostate cancer therapy.Recent findingsOn the basis of observational studies, a general cheap multivitamin that provides the recommended daily values of folic acid, B6, B12 and vitamin D may reduce the risk of a variety of chronic diseases. Selenium supplements at 200 μg/day should be reserved only for men with a deficient level of plasma selenium, but healthy dietary sources should be recommended for most men. Low-dose vitamin E supplements may be adequate for current or recent smokers but not non-smokers. All men should be encouraged to consume healthy dietary sources of vitamin E, regardless of smoking status. Low-dose daily aspirin may be the best over the counter product to utilize as a preventive agent; this statement is made on the basis of the numerous clinical studies that support its use for individuals that qualify after consulting with their physician or a specialist to evaluate current cardiovascular risk. In addition, fish oil supplements have gained acceptance as a possible therapy in high-risk cardiovascular patients.SummaryThe potential future role in prostate cancer should be of interest, and preliminary data is noteworthy. Regardless, all of these supplements have indirect evidence for effects in prostate cancer, but it seems that only a minority of men overall qualify for them currently, with the exception of a low-dose aspirin or multivitamin.

ISSN:0963-0643    

出版商:OVID    

年代:2003

数据来源: OVID