Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amongst men, prostatic adenocarcinoma is the most common cancer and the second most frequent cause of deaths. Widespread PSA measurement have led to earlier diagnosis. Recent clinical trials have tried to show an improvement in the prognosis. Early stages are mainly treated surgically even if local control results are similar with radiotherapy. Radiotherapy is the main stay of treatment for more locally advanced disease, either conventionally or conformational. Adjuvant hormonotherapy has been shown to improve survived as opposed to neoadjuvant hormonotherapy which only has local effects. The treatment of metastatic disease is palliative with the use of antiandrogens. In case of relapse, a second line of hormonotherapy or a chemotherapy is given. However the problem is the lack of effective drugs. Response rates to the main drug treatment are around 10 to 20%. New therapeutic approaches are now based on antimicrotubules agents but it is difficult to evaluate their efficacity. Further clinical trials will provide more information about improvement in survival rates and in quality of life.
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PMID:[Localized or metastatic cancer of the prostate: review of new treatment modalities]. 981 71

Pelvic lymphadenectomy in patients with organ confined prostate cancer (PCa) is of no therapeutic value and is questionable in many patients because of the low incidence of metastases. 49 patients with < or = cT2 b, G1 + 2, PSA < or = 10 ng/ml underwent laparocopic pelvine lymphadenectomy and radical perineal prostatectomy. Only 1 patient (2%) had microscopic metastases which were missed on frozen section. Because of these own results and those reported in the literature we then performed in patients with this constellation the radical perineal prostatectomy without lymphadenectomy (n = 32). The differences present in both groups concerning complication rate and morbidity are due to laparoscopic lymphadenectomy and the learning curve in perineal prostatectomy.
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PMID:[Radical perineal prostatectomy without lymphadenectomy. Patients with cT1 + 2, G1 +2, PSA < or = 10 ng/ml prostate carcinoma]. 1023 35

The morbidity and mortality associated with prostate cancer can almost universally be attributed to the consequences of metastases to the bone. While clinically there have been descriptive reports of these lesions and their detection by bone scan, there is an embrrassing paucity of reports as to the mechanisms of prostate cancer cell trafficking to the bone, adaptation to the bone environment, pertubation of the normal bone reformation process and the events leading to cachexia and death. In recent years, there have been numerous in vitro studies suggesting that PSA and hK2 may play a significant biological role in these events. Also, recent data generated form reverse transcription polymerase chain reaction assays reveal that metastasis to the bone may be an early event which further underscores the need to better understand this complex and critically important process. This commentary highlights several general concepts and a few specific issues related to CaP bone metastasis with the intent of revealing numerous opportunities for further investigation and inquiry.
Cancer Metastasis Rev
PMID:Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone. 1045 76

Prognostic factors for prostatic carcinoma should be significant, independent and clinically important. They should be of practical use, and their determination should be affordable in everyday practice. Prognostic factors may be grouped into patient-related, tumor-related and treatment-related. They should meet certain requirements, such as possession of a clear biological significance, an adequate sample size (possibly more than 150 patients), no patient population bias, an adequate statistical test, such as Cox regression analysis, as well as optimized cut-off values and reproducibility. From a pathologist's view, prognostic factors with established values are grade, margin involvement, capsular penetration, seminal vesical involvement, metastases and invasion of fat in needle biopsies. In contrast to this, factors with little value are, among others, zone location or nuclear shape. If these guidelines for assessment of prognostic factors are not met, the prognostic factors grow exponentially, as an individual patient can only belong to one prognostic group. If one considers all three categories of prognostic factors together, the clinical stage matters most despite all uncertainties. The same holds true for grading; particularly, the well-differentiated grades on biopsy cores have the drawback of being reflected in the specimen only infrequently. The use of biomarkers to give a better prognostic information is also disappointing, as only PSA and PAP have a reliable value among 28 biomarkers. It is of note that new biomarkers are continuously being discovered and examined, such as cyclin A or D. Due to these deficiencies in all three categories of prognostic factors for prostatic carcinoma, prognostic indices in the form of nomograms were constructed. But, if these indices are employed to answer the most important question at the time of diagnosis, i.e., 'is this man a candidate for surveillance?', neoadjuvant treatment plus irradiation, neoadjuvant treatment plus radical prostatectomy, perineal radical prostatectomy, because of a low probability of extracapsular extension or positive lymph nodes, adjuvant therapy after local treatment with curative intent as opposed to progression-based treatment or immediate systemic treatment, let alone intermittent endocrine manipulation, are not reliably possible. The outcomes of the few available studies based on prognostic factors should be studied carefully. If considered, a valuable new way of estimating artificial neural networks is a possibility to come to practical terms.
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PMID:Prognostic factors for carcinoma of the prostate. 1059 92

Pituitary adenomas are usually benign neuroendocrine tumors. However, some of those that are histopathologically undistinguishable behave aggressively and metastasize. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is highly expressed during the development of the brain and pituitary, is detected in some neuroendocrine tumors and might be relevant as a prognostic marker in pituitary tumors. In the present study, we have searched for PSA-NCAM expression in four lineages of rat pituitary transplantable tumors (SMtTW). Each lineage, maintained by serial tumor grafts under the kidney capsule and skin, differed in its GH/Prl secretion, growth rate, and malignant behavior. PSA-NCAM expression, detected by immunohistochemistry and Western blotting and quantified by ELISA, varied according to the SMtTW lineage. The benign tumors, SMtTW2, with a low growth rate never expressed PSA-NCAM. Another benign lineage, SMtTW3, with a high growth rate expressed a low amount of PSA-NCAM. The highest PSA-NCAM expression was seen in tumors that grew beneath the skin, invaded the kidney, and metastasized (SMtTW4). Tumors of the SMtTW10 lineage, which behaved as either benign or malignant tumors, were heterogeneous in terms of PSA-NCAM expression. In this rat transplantable pituitary tumor model, PSA-NCAM expression correlated in decreasing order with: (a) invasiveness (P < 0.0001), (b) metastases (P = 0.004), (c) ability to grow under the skin (P = 0.006), and (d) growth rate under the kidney capsule (P < 0.01), but not with hormone secretion (r = 0.207). This model, which is very similar to the human pathology, suggests that PSA-NCAM evaluation is of interest in the diagnosis of malignancy and the prognosis of human pituitary tumors. In addition, the SMtTW tumors could be instrumental in evaluating the effects of new therapeutic agents modulating PSA-NCAM expression.
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PMID:Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. 1064 57

Approximately 18 % of patients will experience PSA failure only after radical prostatectomy. The rate of clinical (local or systemic) recurrence is in the same range. Clinical recurrence is accompanied by an increasing PSA in almost all cases. Altogether, the 10-year risk of PSA recurrence after radical prostatectomy for clinically localized prostate cancer is about 35 %. PSA relapse precedes the development of metastases by a median time of 8 years. The median survival after the manifestation of metastases is about 4-5 years. To differentiate the reasons of PSA failure, recurrence-free interval, Gleason score and PSA doubling time deliver important information. Patients with a high probability of isolated local failure (PSA relapse later than two years after radical prostatectomy) should undergo a biopsy, if a local radiotherapy is considered. The results of current clinical trials are eagerly awaited to answer the question weather immediate, delayed or intermittent hormonal therapy offer best results in individual cases.
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PMID:[PSA rise after radical prostatectomy]. 1066 89

According to the representative data of the Tumor Registry Munich, 38.1 % of prostate cancer patients received a primary androgen deprivation, whereas 20.5 % had an adjuvant hormonal treatment. Following surgical castration being the most common form of androgen deprivation, 5 alpha-dihydrotestosterone is still present in prostate cancer tissue. Therefore, a maximal androgen blockade (MAB) consisting of a chemical or surgical castration plus a pure or antigonadotropic antiandrogen, has been proposed. Indeed, MAB lowers the dihydrotestosterone-androgen-receptor complex and suppresses the growth-factor dominated signal transduction. This leads to a measurable increase of apoptosis. New is the finding that LHRH as well as LH (for example following surgical castration) are bound by receptors located at the prostate cancer cell. In 30 phase-III trials, MAB has been tested against monotherapy and a cancer-specific survival advantage of 3 to 6 months and a approximately 6-month delay of progression was demonstrated. The most effective form of MAB is the combination of a LHRH agonist - in contrast to surgical castration - with a well-tolerated pure antiandrogen. The quality of life during MAB is low, if a pure antiandrogen such as flutamide is used which leads to rather serious side-effects. At the present time, special indications for MAB are patients with minimal metastases, bone pain at the time of diagnosis, a neoadjuvant or adjuvant application in combination with a radical prostatectomy or radiotherapy and particularly intermittent androgen deprivation which is tested at the present time in at least 5 international studies. An endocrine withdrawal syndrome is observed in approximately 30 % of patients, if, following a PSA-relapse, the antiandrogen is discontinued. Little notice has been given to the use of prognosticators for the decision, whether a MAB is useful or not. Patients with good prognostic factors as defined by Sylvester have a clear advantage, if MAB is compared to monotherapy, whereas patients with a pure prognosis did not benefit. In addition to these prognostic factors up-front, the PSA dynamics under an initial MAB may be employed for the decision, if this form of androgen deprivation is to be continued or not. In essence, in contrast to a general use of MAB a more differential application based on quality-of-life issues and prognosis should be preferred.
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PMID:[Maximal androgen blockade]. 1066 93

The local recurrence rate after radical prostatectomy for prostate cancer has varied across studies but seems sufficiently high (20 to 40%) to warrant a reappraisal of the oncological usefulness of this procedure performed in isolation using current techniques. Local recurrence can be either biological or clinical. In biological recurrences, the only abnormality is recurrent PSA elevation. It has been suggested that this event, even in the absence of ultrasound changes or histological documentation, should lead to additional therapy, usually in the form of local radiation therapy, and that the efficacy criterion for this treatment should be a fall in PSA to undetectable levels. However, differences in the "ultrasensitive" assays used to detect PSA pose a serious obstacle to comparisons of published studies. Furthermore, in most publications, the pathological stage is more severe than the clinical stage, and this clinical underestimation of disease severity complicates the evaluation of recurrence rates. In clinical recurrences, rectal digital examination or endorectal ultrasonography show abnormalities and, more importantly, examination of a biopsy specimen establishes that these abnormalities are due to malignant disease. Symptoms may or may not be present. Many authors, particularly in Europe, feel that only clinical recurrences warrant additional treatment, usually in the form of radiation therapy. However, as a preliminary, all available imaging techniques should be used to confirm that the absence of metastases. A valuable tool in this situation is the study of PSA kinetics (elevation rate or postoperative doubling time). If the recurrence seems local, radiation therapy alone is the best initial option, since concomitant hormone therapy leads to a decrease in PSA levels even in the presence of metastatic disease, thus depriving the patient and physician of a valuable therapeutic test. Success rates after radiation therapy for recurrences have varied widely across studies. Some authors consider that this treatment approach is ineffective or provides only transient benefits. Follow-ups were often short, particularly given the considerable variability of the natural history of prostate cancer. The enthusiasm initially generated by radical prostatectomy should be tempered, at least regarding the possibility of a complete cure.
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PMID:[Local recurrence after radical prostatectomy for prostatic cancer]. 1076 25

Capromab Pendetide imaging illustrates the successful translation of monoclonal antibody technology from the laboratory to the clinic. It provides a means of identifying otherwise occult soft tissue metastases in patients with adenocarcinoma of the prostate. When utilized with other clinical, pathological and laboratory findings, Capromab Pendetide imaging enables more accurate disease staging and monitoring than is afforded by other imaging modalities such as CT and MRI. In the primary disease setting Capromab Pendetide imaging should be reserved for use in patients with negative bone scans who are at high risk for metastatic disease based on such factors as advanced clinical stage, high Gleason score and significantly elevated serum PSA or alkaline phosphatase. Due to low sensitivity for small-volume disease, a negative Mab scan may not eliminate the need for a staging lymph node dissection but should encourage further consideration of local treatment options. Capromab Pendetide should be used with caution in patients at low risk for metastatic disease. Positive scan findings in low risk patients should be confirmed before altering the treatment plan since some false positive scans should be anticipated in a population with low disease prevalence. Capromab Pendetide imaging has not been shown to be reliable in determining the local extent of the primary tumor but new techniques involving co-registration of SPECT and CT images show promise in this regard. In the patient with recurrent disease following primary therapy, the predictive value of Capromab Pendetide imaging of the prostate or prostate fossa is limited, particularly following RT. Its more important role in this setting is to identify lymph node metastases in the high risk patient with a negative bone scan who might otherwise be a candidate for local salvage therapy. A large prospective study is needed for confirmation, but preliminary data suggest that Capromab Pendetide imaging is helpful in identifying those patients with PSA elevation after radical prostatectomy who are most likely to benefit from salvage RT. As with any imaging technique, Capromab Pendetide has strengths and weaknesses that must be understood to maximize patient benefit by utilizing the scan in clinical settings where it is most likely to be useful and least likely to be misleading. Capromab Pendetide is a technically demanding procedure best performed and interpreted at sites with experience and expertise.
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PMID:Capromab Pendetide imaging of prostate cancer. 1080 17

A recombinant vaccinia virus encoding human prostate-specific antigen (rV-PSA) was administered as three consecutive monthly doses to 33 men with rising PSA levels after radical prostatectomy, radiation therapy, both, or metastatic disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7), and 2.65 x 10(8) plaque forming units. Ten patients who received the highest dose also received 250 microg/m2 granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjunct. No patient experienced any virus-related effects beyond grade I cutaneous toxicity. Pustule formation and/or erythema occurred after the first dose in all 27 men who received > or =2.65 x 10(7) plaque forming units. GM-CSF administration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or without GM-CSF were stable for at least 6 months after primary immunization. Nine patients remained stable for 11-25 months; six of these remain progression free with stable PSA levels. Immunological studies demonstrated a specific T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is safe and can elicit clinical and immune responses, and certain patients remain without evidence of clinical progression for up to 21 months or longer.
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PMID:A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer. 1081 80


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