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Salvage radiotherapy for PSA failure after radical prostatectomy.

BACKGROUND AND PURPOSE: Prostate-specific antigen (PSA) failure after radical prostatectomy is a common clinical scenario, and there is no consensus on how it should be managed. Salvage radiation to the prostatic bed is a potentially curative treatment option, and is the subject of this review. Patient selection, and the efficacy and toxicity of treatment will be discussed, and recommendations made for current practice and future studies. METHODS: An English language MEDLINE search was performed, limited to the years 1989-2000, using the MeSH headings 'prostatic neoplasms' and 'radiotherapy'. The 660 abstracts identified were reviewed, and articles concerning patient selection for, or outcome of, post-operative radiation to the prostatic bed selected. After exclusion of articles concerning adjuvant, rather than salvage, radiation, this left a total of 22 case series, including 1062 patients for the review of treatment efficacy. RESULTS AND CONCLUSIONS: The quality of the evidence makes it difficult to form a judgment regarding the efficacy of salvage radiation following radical prostatectomy, particularly in men with a PSA level in the range 0.01-0.2 ng/ml. Salvage radiation may be more effective given earlier rather than later. These considerations have important consequences for the interpretation of current trials of adjuvant radiation following radical prostatectomy.

Bone Neoplasms↗

[Analysis of loss of heterozygosity on chromosome 6 in human prostate carcinoma and prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the significance of loss of heterozygosity (LOH) on chromosome 6 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues after tissue microdissection. LOH of chromosome 6 was detected by PCR based microsatellite polymorphism analysis technique using 20 pairs of microsatellite primers in 10 prostate carcinoma cases and 10 high grade PIN cases. RESULTS: Allelic loss at one or more loci was observed on chromosome 6 in 8 of 10 prostate carcinoma cases. 6q21-6q23 and 6q25-6q27 were two of LOH high frequency regions. 5 high grade PIN cases had LOH detected on chromosome 6. CONCLUSIONS: Two high frequency LOH regions were detected on chromosome 6 of prostate carcinoma. Cyclin C, IGF2R genes were two candidate tumor suppressor genes located in these two regions, they may be involved in the initiation and progression of prostate cancer.

Aged↗

Correlation of genetic and immunodetection of TP53 mutations in malignant and benign prostate tissues.

The prognostic value of the p53 gene (TP53), the most commonly mutated gene in human cancers, has been well established for several cancer types. However, because varying frequencies of TP53 mutations have been identified in prostatic adenocarcinoma (CaP) by genetic and immunohistochemical (IHC) studies, the role of TP53 in CaP tumorigenesis is currently unresolved. These experimental discrepancies could be caused by tissue heterogeneity within prostatic neoplasms, variations in experimental protocols, or other factors. Thus, the goal of this study was to develop a reliable IHC approach for the detection of p53 in archival prostate tissue. The authors evaluated four p53 antibodies, CM-1, 1801, DO-1, and DO-7, for their ability to reveal p53. They chose two reference CaP cell lines, 26 patient specimens (including eight benign prostatic hyperplasias (BPHs), 16 CaPs, and two lymph node metastases), one prostate and nine kidney cell lines for p53 analysis. The TP53 status of these samples was characterized using single-strand conformational polymorphism (SSCP) analysis of RNA/PCR products and sequencing. IHC detection of p53 was markedly enhanced by using the combination of microwave heat-induced antigen unmasking and a cocktail of the DO-1 and DO-7 antibodies. This approach identified 14 of 15 (93%) cell lines and patient samples having TP53 missense mutations in the exons 5 to 8 region. Of the 21 patient samples and cell lines that were either normal by SSCP or expressed p53 mutations that are not expected to stain, 18 (86%) were immunonegative. Because of this good correlation between molecular and IHC analysis, this approach may help to resolve the uncertainty about TP53 in CaP tumorigenesis.

Adenocarcinoma↗

[Prostatic type papillary tumor of the urethra with endocrine cells. Immunohistochemical study].

A peculiar variety of prostatic neoplasm harbouring a constellation of endocrine cells is reported. The tumor had a papillary growth projecting into the lumen of the prostatic urethra. The histological appearances were somewhat unusual. One fragment showed a typical feature of a prostatic-type polyp. However, much of the tissue were covered by a dysplastic epithelium. Adenomatous transformation of prostate-type polyp or "endometrial" adenocarcinoma could be considered.

APUD Cells↗

Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.

PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Humans↗

The initiation of breast and prostate cancer.

The agents responsible for the initiation of human mammary and prostatic cancers remain unidentified. Population migration studies on breast and prostate cancer risk have revealed that incidence rates in migrants from low-risk to high-risk "Westernized" countries rise over time to match those of the host populations. The parallels suggest that the two diseases may share a common aetiology, with changes in diet, rather than in environment, being responsible for the migration-related increases in cancer incidence. Genotoxins, such as polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, are formed when foodstuffs are cooked at elevated temperatures and can be extracted with solvents: other genotoxins may only be released from cooked proteins when digestion occurs in the gastrointestinal tract. Human mammary and prostatic epithelial cells are known to be capable of metabolically activating members of different classes of chemical carcinogens to DNA-reactive species and, in rodents, five out of six mammary carcinogens can also induce prostatic neoplasms. Genotoxins have been detected in some 40% of breast lipid and milk samples donated by UK-resident women but the agents, currently thought to be of dietary origin, have not been characterized or identified as yet. Reduction mammoplasty and lactation both reduce breast cancer risk and the reduction is proportional either to the amount of tissue removed or to the total duration of lactation. As DNA damage has been detected in otherwise untreated mammary epithelial cells isolated both from breast tissue and from breast milk, we have proposed that reduction mammoplasty and lactation reduce risk through a common mechanism, i.e. the loss of pre-malignant cells. Further research, perhaps aimed particularly at the characterization of all the carcinogens formed when different dietary components are cooked in different ways, should succeed in identifying the agents that initiate breast and prostate cancer.

Animals↗

[Cytodiagnosis of prostatic and testicular neoplasms].

Struck by delays in the diagnosis of carcinomas of the prostate and testis, the authors have developed a method for cytological study by puncture of those organs. During a 7 year period, they saw 100 carcinomas of the prostate, 94% of which had already spread beyond the prostate with bone metastases in 48%. During the same period, 18 carcinomas of the testis were seen, with several erroneous differential diagnoses which led to a delay in diagnosis (mean: 12 weeks). The authors use a Franzen-type aspiration needle which makes possible puncture and aspiration of the tumour zone without hospitalisation of the patient. Cytological diagnosis implies the need for considerable experience, bearing in mind that in particular certain excessively deep punctures of the prostate may yield cells from the seminal vesicles which lead to an incorrect diagnosis of carcinoma of the prostate. Such aspiration cytology may be used to differentiate between benign and malignant tumours, as well as providing a more accurate diagnosis in terms of the type of tumour and the degree of differentiation.

Biopsy, Needle↗

[Solitary hypermetabolic bone focus in the initial extension study of a prostate carcinoma].

56 year old male who was diagnosed of Prostatic Neoplasm by transrectal biopsy after elevated PSA level was found by chance in a routine control. The initial extension study with abdominal and pelvic CT did not show significant radiological abnormalities. This was followed by a whole body bone scintigraphy with 99mTc-MDP that showed a solitary hypermetabolic lesion within skull. A SPECT study placed this lesion at the left occipital region. An MRI and a CT head scan were carried out to characterize the isotopic lesion, finding no bone abnormalities to justify the mentioned uptake. Given the absence of a radiological benign diagnosis, a further FDG-PET scan was carried out which did not show either increased glycolytic activity at the left occipital region, or in the prostatic gland. In order to guide the biopsy, a CT head scan was repeated which showed what appeared to be an incipient blastic lesion in the scale of the left occipital bone, establishing the differential diagnosis between a metastasis and a benign process. The anatomopathologic analysis of the bone tissue describes a necrotic process without inflammatory reaction (osteonecrosis).

Adenocarcinoma↗

Magnetic resonance imaging of the pelvis: prostate and urinary bladder.

Magnetic resonance imaging has opened up a new horizon in the evaluation of the male pelvis. Its direct multiplanar imaging and display of the unique tissue contrast allows for the demonstration of prostate anatomy. Prostatic disease, even when confined to the gland, is easily depicted. However, one cannot distinguish benign from malignant processes. In a patient with a known prostatic neoplasm, magnetic resonance is useful as a staging modality. Accuracy in the staging of prostatic malignancies by MRI surpasses that of ultrasound or CT. In the evaluation of the urinary bladder, the greatest advantage of magnetic resonance is its ability to differentiate between a normal bladder, and other pathologic conditions affecting the bladder, including inflammatory, congestive and neoplastic processes. In the evaluation of bladder carcinoma, magnetic resonance is useful as a staging modality. Clinical application of magnetic resonance is just beginning and therefore, the full potential of the modality has yet to be explored.

Adult↗

Secondary solid neoplasms of the prostate: a clinico-pathological series of 51 cases.

The incidence, presentation, and macroscopic and histological features of secondary solid neoplasms of the prostate gland are described with reference to their differential diagnoses. A continuous series of autopsy and surgical cases from the Royal London Hospital from 1907 to the present yielded a total of 51 secondary neoplasms involving the prostate: 24 at post-mortem examination and 27 surgical specimens. The histology of these specimens was re-examined. In 34 cases, tumour reached the prostate by direct spread: 29 from the bladder and 5 from the rectum. The most common primary sites of metastases to the prostate were lung (eight cases) and pancreas (two cases). There were isolated examples of metastases from the bladder, rectum, skin (malignant melanoma), breast, eye (malignant melanoma), adrenal cortex and gallbladder. Secondary neoplasms represented 2.1% of all neoplasms in surgical specimens, a similar proportion of the total number of malignant solid neoplasms as secondary tumours at other sites in the genitourinary tract. The patients were usually symptomatic, presenting with prostatism, haematuria or pelvic pain, almost always in those with widely disseminated disease.

Aged↗

Role of galectin-8 as a modulator of cell adhesion and cell growth.

Galectin-8 belongs to the family of tandem-repeat type galectins. It consists as several isoforms, each made of two domains of approximately 140 amino-acids, both having a carbohydrate recognition domain (CRD). These domains are joined by a 'link peptide' of variable length. The human galectin-8 gene covers 33 kbp of genomic DNA. It is localized on chromosome 1 (1q42.11) and contains 11 exons. The gene produces by alternative splicing 14 different transcripts, altogether encoding 6 proteins. Galectin-8, like other galectins, is a secreted protein. Upon secretion galectin-8 acts as a physiological modulator of cell adhesion. When immobilized, it functions as a matrix protein equipotent to fibronectin in promoting cell adhesion by ligation and clustering of a selective subset of cell surface integrin receptors. Complex formation between galectin-8 and integrins involves sugar-protein interactions and triggers integrin-mediated signaling cascades such as Tyr phosphorylation of FAK and paxillin. In contrast, when present in excess as a soluble ligand, galectin-8 (like fibronectin) forms a complex with integrins that negatively regulates cell adhesion. Such a mechanism allows local signals emitted by secreted galectin-8 to specify territories available for cell adhesion and migration. Due to its dual effects on the adhesive properties of cells and its association with fibronectin, galectin-8 might be considered as a novel type of a matricellular protein. Galectin-8 levels of expression positively correlate with certain human neoplasms, prostate cancer being the best example studied thus far. The overexpressed lectin might give these neoplasms some growth and metastasis related advantages due to its ability to modulate cell adhesion and cellular growth. Hence, galectin-8 may modulate cell-matrix interactions and regulate cellular functions in a variety of physiological and pathological conditions.

Animals↗

A profile of metastatic carcinoma of the spine.

Metastatic bone disease in 322 patients was analyzed to assess the frequency and behavior of disseminated carcinoma to the vertebral column. Breast, lung, and prostate neoplasms were the most frequent tumors of origin in the 55% of patients who had vertebral lesions. The lumbar spine was the site of the greatest number of metastases. Back pain did not occur in 36% of the 179 patients with spinal disease. Cord compression occurred in 20% of the patients with vertebral involvement, and prostate tumors were the most frequent neoplasm to cause epidural spinal cord impingement. Hypernephroma was the most common cancer to present as a neurologic deficit secondary to an undetected primary malignancy.

Adult↗

[A retrospective study of bone metastases distribution on 420 whole body scans].

UNLABELLED: 420 patients with cancer of breast, prostate, lung and colon were investigated through 99mTc Methylene-diphosphonate whole body scintigraphy. The presence of pathologic radiotracer uptake was qualitatively and quantitatively analyzed in order to establish the metastases distribution. Patient selection was realized over 2455 whole body scintigraphies effectuated between 1998 and 2001 in our Nuclear Medicine Service. All selected cases were metastases with known origin primary cancer. RESULTS: Using the Qui-square Test we have compared the frequency of nine well delimited skeleton regions involved like metastatic site in the different cancer types. We have found a significant statistic difference of the range of frequency only between breast and prostate cancers as well as between pulmonary and prostate cancers. The mean number of the metastatic involved skeletal regions was significantly greater in breast and prostate cancers in comparison with lung and colon cancers (p < 0.0001). The higher metastases site frequency was the rachis, than the pelvis, the ribs and the sternum. The skull metastases localization is more frequent in breast cancer in comparison with all other cancers (7.67% versus less than 4% in other cancer types). The pelvis was more involved for the metastatic process in prostate neoplasm. On the other hand, the highest mean anatomic sites number per patient was found in breast cancer (5.7) and prostate cancer (4.8) related to colon (3.3) and lung (3.0) cancers. CONCLUSIONS: Even some particularities were evident, in our study, between the metastases distribution in these four cancer types, the data are not sufficient to sustain the existence of a characteristic pattern related to the primary cancer origin. Metastases localization could be, however, related to the metastazation mechanism.

Algorithms↗

Clinical and in vitro magnetic resonance imaging of prostatic carcinoma.

Magnetic resonance imaging (MRI) of the prostate was accomplished in 10 patients who subsequently had surgical exploration for histologic confirmation and tumor staging. Eight patients were found to have carcinoma of the prostate. Two patients had malignancies of the urinary bladder and were treated with radical resection of the bladder and prostate. The prostatic glands in the latter two patients were free of tumor. One gland was entirely normal; the other had extensive acute and chronic prostatitis. Two resected prostates with carcinoma and one normal prostate were available for in vitro MRI in a clinical magnetic resonance unit. The MRI finding of prostatic carcinoma was heterogeneous signal patterns, seen best on T2-weighted studies. A similar pattern was identified in the gland with acute and chronic prostatitis. There was a homogeneous MRI signal pattern of the normal prostate gland examined in vitro. In two instances, the MRI studies were accurate for the identification of tumor spread to the seminal vesicles, not diagnosed at the time of surgical resection. Microscopic metastatic disease of the lymph nodes in four patients was not identified by MRI.

Adenocarcinoma↗

[Cytologic diagnosis of prostatic carcinoma by transrectal prostatic aspiration biopsy].

Since October 1982, 500 cases of transrectal fine needle aspiration biopsy have been done. Among them, 486 cases (97.2%) got prostate epithelium enough for diagnosis but 14 cases (2.8%) failed. The cytologic results showed prostatic cancer in 100 cases (20.5%), bladder cancer with metastasis to prostate in 7 cases (1.4%), suspicious cancer in 4 cases (0.82%), hyperplasia of prostate 251 cases (51.64%), normal prostate 104 cases (21.3%), tuberculosis one case (0.2%), lithiasis one case (0.2%), purulent prostatitis 4 cases (0.82%), granulomatous prostatitis 6 cases (1.23%), and insufficient epithelium for diagnosis in 8 cases (1.64%). In this series, there were one false positive and two false negative by Franzen's technique. Among 41 cases received further treatment, 35 prostate specimen were available for regular pathological study. The consistent rate between pathological and cytologic diagnosis was 85.4%. In a word, transrectal prostatic aspiration is an outstanding safe and practical method for the diagnosis of prostate cancer.

Adult↗