Hospital Carabineros of Chile

Villa Presidente Frei, Chile

Hospital Carabineros of Chile

Villa Presidente Frei, Chile
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Murray N.P.,Hospital Carabineros of Chile | Murray N.P.,Finis Terrae University | Ruiz M.A.,Hospital Carabineros of Chile | Miranda G.M.,Hospital Carabineros of Chile
ecancermedicalscience | Year: 2017

Patients diagnosed with severe aplastic anaemia and without a compatible bone marrow transplant donor are treated with immunosuppressive therapy. These patients are found with time to develop a clonal disease such as myelodysplasia or paroxysmal nocturnal haemoglobinuria. However, the development of plasma cell dyscrasias is rare. We report the case here of a patient treated with immunosuppressive therapy who went on to develop myeloma 11 months after being diagnosed with severe aplastic anaemia. We include here a review of the literature. © 2017 the authors.


Murray N.P.,Hospital Carabineros Of Chile | Murray N.P.,Finis Terrae University | Fuentealba C.,Hospital Carabineros Of Chile | Reyes E.,Hospital Carabineros Of Chile | And 2 more authors.
Archivos Espanoles de Urologia | Year: 2017

OBJECTIVE: The limitations of total serum PSA values remains problematic; nomograms may improve the prediction of a positive prostate biopsy (PB). We compare in a prospective study of Chilean men with suspicion of prostate cancer due to an elevated total serum PSA and/or abnormal digital rectal examination, the use of two on-line nomograms with the detection of primary malignant circulating prostate cells (CPCs) to predict a positive PB for high risk prostate cancer. METHODS: Consecutive men with suspicion of prostate cancer underwent 12 core TRUS prostate biopsy. Age, total serum PSA and percent free PSA, family history, ethnic origin and prostate ultrasound results were registered. Risk assessment was performed using the online nomograms. The European Randomized Study of Screening for Prostate Cancer derived Prostate Risk Indicator (SWOP-PRI) and the North American Prostate Cancer Prevention Trail derived Prostate Risk Indicator (PCPT-CRC) were used to calculate risk of prostate cancer. Immediately before PB an 8 ml blood sample was taken to detect CPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunomarcation with anti-PSA and anti-P504S. Biopsies were classified as cancer/no-cancer, CPC detection test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for total serum PSA, free percent, PSA, SWOP-PRI, PCPT-CRC and CPCs were calculated and compared. Diagnostic yields were calculated, including the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed. RESULTS: 1,223 men aged > 55 years were analyzed, 467 (38.2%) had a biopsy positive for cancer of which 114/467 (24.45) complied with the criteria for active observation; 177/467 (36.8%) were Gleason 7 or higher. Discriminative power of detecting prostate cancer, showed areas under the curve of total PSA 0.559, SWOP nomogram 0.687, PCPTRC nomogram 0.716, free percent PSA 0.765 and CPC detection 0.844. CPC detection was superior to the other models (p<0.0001). Using the recommended cutoff values, free percent PSA avoided 81% of biopsies missing 58% of significant cancers; for the other models the values were SWOP 75% and 56%; PCPTRC 61% and 62%, CPC detection 57% and 4% respectively. CONCLUSIONS: CPC detection was superior to the other models in predicting the presence of clinically significant prostate cancer at initial biopsy; potentially reduces the number of unnecessary biopsy while missing few significant cancers. Being a positive/negative test it avoids defining a cutoff value which may differ between populations. Multicenter studies to validate this method are warrented.


Murray N.P.,Hospital Carabineros of Chile | Murray N.P.,Finis Terrae University | Aedo S.,Finis Terrae University | Reyes E.,Diego Portales University | And 4 more authors.
BJU International | Year: 2016

Objective: To establish a prediction model for early biochemical recurrence based on the Cancer of the Prostate Risk Assessment (CAPRA) score and the presence of secondary circulating prostate cells (CPCs). Patients and Methods: We conducted a prospective single-centre study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinicopathological findings were used to calculate the CAPRA score. At 90 days after surgery, blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs were identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen (PSA) but not CD45. The CPC test results were defined as positive or negative. Patients were followed up for up to 5 years and biochemical recurrence was defined as a PSA level >0.2 ng/mL. The validity of the CAPRA score was calibrated using partial validation, and Cox proportional hazard regression to build three models: a CAPRA score model, a CPC model and a CAPRA/CPC combined model. Results: A total of 321 men, with a mean age of 65.5 years, participated in the study. After 5 years of follow-up the biochemical recurrence-free survival rate was 98.55%. For the model that included CAPRA score there was a hazard ratio (HR) of 7.66, for the CPC model there was an HR of 34.52 and for the combined model there were HRs of 2.60 for CAPRA score and 22.5 for CPC. Using the combined model, 23% of men changed from the low-risk to the high-risk category, or vice versa. Conclusion: The incorporation of CPC detection significantly improved the model's discriminative ability in establishing the probability of biochemical recurrence; patients in the high-risk group according to CAPRA score who are negative for CPCs have a much better prognosis. The addition of CPC detection gives clinically significant information to aid the decision on who may be eligible for adjuvant therapy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd


PubMed | Hospital Carabineros of Chile, Hospital DIPRECA, Diego Portales University and Finis Terrae University
Type: Journal Article | Journal: BJU international | Year: 2016

To establish a prediction model for early biochemical recurrence based on the Cancer of the Prostate Risk Assessment (CAPRA) score and the presence of secondary circulating prostate cells (CPCs).We conducted a prospective single-centre study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinicopathological findings were used to calculate the CAPRA score. At 90 days after surgery, blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs were identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen (PSA) but not CD45. The CPC test results were defined as positive or negative. Patients were followed up for up to 5 years and biochemical recurrence was defined as a PSA level >0.2 ng/mL. The validity of the CAPRA score was calibrated using partial validation, and Cox proportional hazard regression to build three models: a CAPRA score model, a CPC model and a CAPRA/CPC combined model.A total of 321 men, with a mean age of 65.5 years, participated in the study. After 5 years of follow-up the biochemical recurrence-free survival rate was 98.55%. For the model that included CAPRA score there was a hazard ratio (HR) of 7.66, for the CPC model there was an HR of 34.52 and for the combined model there were HRs of 2.60 for CAPRA score and 22.5 for CPC. Using the combined model, 23% of men changed from the low-risk to the high-risk category, or vice versa.The incorporation of CPC detection significantly improved the models discriminative ability in establishing the probability of biochemical recurrence; patients in the high-risk group according to CAPRA score who are negative for CPCs have a much better prognosis. The addition of CPC detection gives clinically significant information to aid the decision on who may be eligible for adjuvant therapy.


Murray N.P.,Hospital Carabineros of Chile | Murray N.P.,Major University | Murray N.P.,Institute of Bio Oncology | Reyes E.,Hospital Carabineros of Chile | And 4 more authors.
Journal of Oncology | Year: 2014

Objective. To determine if primary circulating prostate cells (CPCs) are found in all men with prostate cancer. Methods and Patients. A prospective study, to analyze all men with an elevated PSA between 4.0 and 10.0 ng/mL undergoing initial biopsy. Primary CPCs were obtained by differential gel centrifugation and detected using standard immunocytochemistry using anti-PSA; positive samples underwent a second process with anti-P504S. A malignant primary CPC was defined as PSA (+) P504S (+) and a test positive if 1 cell/4 mL was detected. Biopsy results were registered as cancer/no-cancer, number of cores positive, and percent infiltration of the cores. Results. 328/1123 (29.2%) of the study population had prostate cancer diagnosed on initial biopsy, and 42/328 (12.8%) were negative for primary CPCs. CPC negative men were significantly older, and had lower PSA levels, lower Gleason scores, and fewer positive cores and with infiltration by the cancer. 38/42 (91%) of CPC negative men complied with the criteria for active surveillance in comparison with 34/286 (12%) of CPC positive men. Conclusions. Using primary CPC detection as a sequential test to select men with an elevated PSA for biopsy, the risk of missing clinically significant prostate cancer is minimal when the patient is primary CPC negative; less than 0.5% of all primary CPC negative men had a clinically significant prostate cancer. © 2014 Nigel P. Murray et al.


Murray N.P.,Hospital Carabineros of Chile | Murray N.P.,Institute BioOncologia | Murray N.P.,Major University | Reyes E.,Diego Portales University | And 7 more authors.
Journal of Oncology | Year: 2013

Introduction. Developments in immunological and quantitative real-time PCR-based analysis have enabled the detection, enumeration, and characterization of circulating tumor cells (CTCs). It is assumed that the detection of CTCs is associated with cancer, based on the finding that CTCs can be detected in all major cancer and not in healthy subjects or those with benign disease. Methods and Patients. Consecutive men, with suspicion of prostate cancer, had blood samples taken before prostate biopsy; mononuclear cells were obtained using differential gel centrifugation and CPCs detecting using anti-PSA immunocytochemistry. Positive samples underwent further classification with anti-P504S. Results. 329 men underwent prostate biopsy; of these men 83 underwent a second biopsy and 44 a third one. Of those with a biopsy negative for cancer, 19/226 (8.4%) had CPCs PSA (+) P504S (-) detected at first biopsy, 6/74 (8.1%) at second biopsy, and 5/33 (15.2%) at third biopsy. Men with cancer-positive biopsies did not have PSA (+) P504S (-) CPCs detected. These benign cells were associated with chronic prostatitis. Conclusions. Patients with chronic prostatitis may have circulating prostate cells detected in blood, which do not express the enzyme P504S and should be thought of as benign in nature. © 2013 Nigel P. Murray et al.


Murray N.P.,Hospital Carabineros of Chile | Murray N.P.,Major University | Murray N.P.,Institute of Bio Oncology | Reyes E.,Hospital Carabineros of Chile | And 7 more authors.
International Journal of Molecular Medicine | Year: 2012

The presence of cells positive for cytokeratins or prostate-specific antigen (PSA) in bone marrow aspirates (BMAs) has been used to indicate the presence of micrometastasis. The aim of this prospective study of prostate cancer patients was to determine the presence of prostate cells in blood and BMAs and to compare them with bone marrow biopsy touch prep samples. The results indicated that there was a satisfactory concordance between circulating prostate cells (CPCs) in blood and disseminated tumor cells (DTCs) in BMAs for all Gleason scores (κ>0.50). However, neither were concordant with the presence of prostate cells in bone marrow biopsies except for high-grade tumors, Gleason 8 and 9. Phenotypic characteristics of CPCs and DTCs were identical (κ>0.9) but were different than cells detected in bone marrow biopsies (κ<0.2). The expression of matrix metalloproteinase-2 (MMP-2) in bone marrow biopsies was positively associated with the Gleason score (trend Chi-squared <0.05) and may explain the differences between the presence of DTCs and the presence of prostate cells in bone marrow biopsies. If the presence of DTCs was used to indicate micrometastatic disease, 20% of patients would be misclassified compared to micrometastasis defined as patients with a positive biopsy. This may have clinical implications for patients with low-grade tumors.


The presence of cells positive for cytokeratins or prostate-specific antigen (PSA) in bone marrow aspirates (BMAs) has been used to indicate the presence of micrometastasis. The aim of this prospective study of prostate cancer patients was to determine the presence of prostate cells in blood and BMAs and to compare them with bone marrow biopsy touch prep samples. The results indicated that there was a satisfactory concordance between circulating prostate cells (CPCs) in blood and disseminated tumor cells (DTCs) in BMAs for all Gleason scores (>0.50). However, neither were concordant with the presence of prostate cells in bone marrow biopsies except for high-grade tumors, Gleason 8 and 9. Phenotypic characteristics of CPCs and DTCs were identical (>0.9) but were different than cells detected in bone marrow biopsies (<0.2). The expression of matrix metalloproteinase-2 (MMP-2) in bone marrow biopsies was positively associated with the Gleason score (trend Chi-squared <0.05) and may explain the differences between the presence of DTCs and the presence of prostate cells in bone marrow biopsies. If the presence of DTCs was used to indicate micrometastatic disease, 20% of patients would be misclassified compared to micrometastasis defined as patients with a positive biopsy. This may have clinical implications for patients with low-grade tumors.


PubMed | Hospital Carabineros of Chile
Type: Journal Article | Journal: Asian Pacific journal of cancer prevention : APJCP | Year: 2016

To determine the utility of primary circulating prostate cells (CPC) for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomogram.A single centre prospective study of men with prostate cancer treated with radical prostatectomy was conducted between 2004 and 2014. Clinicalpathological details were registered, along with total serum PSA presurgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Primary circulating prostate cells were obtained using differential gel centrifugation and detected using standard immunocytochemistry with antiPSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values were calculated using the Walz nomagram and CPC detection.A total of 285 men participated, of whom 103/285 (36.1%) suffered biochemcial failure; 32/103 (31.1%) within two years of radical prostatectomy. Men with higher Gleason scores, higher pathological stage, infiltration of the surgical margin or prostate capsule and infiltration of seminal vesicles were more likely to undergo biochemical failure. There was a significant increase in the frequency of biochemical failure with increasing number of CPCs detected (p<0.0004 Chi squared for trend) and increasing percent prediction for the Walz nomogram (p<0.0001 Chi squared for trends). The positive predictive value of primary CPC detection, even using a cutoff point of 4 cells/sample was very low.The detection of primary CPCs in men as a prognostic factor pretreatment fails to identify those at high risk of biochemical failure within two years of curative therapy. This is in keeping with their biological significance, that the majority of them will be eliminated by the primary therapy and thus have no influence on the subsequent clinical history of the patient.


PubMed | Hospital Carabineros of Chile
Type: Journal Article | Journal: Asian Pacific journal of cancer prevention : APJCP | Year: 2016

Sequential use of circulating prostate cell (CPC) detection has been reported to potentially decrease the number of unnecessary prostate biopsies in men suspected of prostate cancer. In order to determine the real world effectiveness of the test, we present a prospective study of men referred to two hospitals from primary care physicians, one using CPC detection to determine the necessity of prostate biopsy the other not doing so.Men with a suspicion of prostate cancer because of elevated PSA >4.0ng/ml or abnormal DRE were referred to Hospitals A or B. In Hospital A all underwent 12 core TRUS biopsy, in Hospital B only men CPC (+), with mononuclear cells obtained by differential gel centrifugation identified using double immunomarking with antiPSA and antiP504S, were recommended to undergo TRUS biopsy. Biopsies were classifed as cancer or nocancer. Diagnostic yields were calculated, including the number of posible biopsies that could be avoided and the number of clinically significant cancers that would be missed.Totals of 649 men attended Hospital A, and 552 men attended Hospital B; there were no significant differences in age or serum PSA levels. In Hospital A, 228 (35.1%) men had prostate cancer detected, CPC detection had a sensitivity of 80.7%, a specificity of 88.6%, and a negative predictive value of 89.5%. Some 39/44 men CPC negative with a positive biopsy had low grade small volume tumors. In Hospital B, 316 (57.2%) underwent biopsy. There were no significant differences between populations in terms of CPC and biopsy results. The reduction in the number of biopsies was 40%.The use of sequential CPC testing in the real world gives a clear decision structure for patient management and can reduce the number of biopsies considerably.

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