Pressure ulcers: the last mile in the COVID-19 road

Edmundo Ziede,Eduardo Orellana,Rodrigo Tejos,Michel Olivera,Susana Searle 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.1

Prostate Cancer Screening in the Fit Chilean Elderly: a Head to Head Comparison of Total Serum PSA versus Age Adjusted PSA versus Primary Circulating Prostate Cells to Detect Prostate Cancer at Initial Biopsy

Murray, Nigel P.,Reyes, Eduardo,Orellana, Nelson,Fuentealba, Cynthia,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Prostate cancer is predominately a disease of older men, with a median age of diagnosis of 68 years and 71% of cancer deaths occurring in those over 75 years of age. While prostate cancer screening is not recommended for men >70 years, fit elderly men with controlled comorbidities may have a relatively long life expectancy. We compare the use of age related PSA with the detection of primary malignant circulating prostate cells mCPCs to detect clinically significant PC in this population. Materials and Methods: All men undergoing PC screening with a PSA >4.0ng/ml underwent TRUS 12 core prostate biopsy (PB). Age, PSA, PB results defined as cancer/no-cancer, Gleason, number of positive cores and percentage infiltration were registered. Men had an 8ml blood sample taken for mCPC detection; mononuclear cells were obtained using differential gel centrifugation and mCPCs were identified using immunocytochemistry with anti-PSA and anti-P504S. A mCPC was defined as a cell expressing PSA and P504S; a positive test as at least one mCPC detected/sample. Diagnostic yields for subgroups were calculated and the number of avoided PBs registered. Esptein criteria were used to define small grade tumours. Results: A total of 610 men underwent PB, 398 of whom were aged <70yrs. Men over 70 yrs had: a higher median PSA, 6.24ng/ml versus 5.59ng/ml (p=0.04); and a higher frequency of cancer detected 90/212 (43%) versus 134/398 (34%) (p=0.032). Some 34/134 cancers in men <70yrs versus 22/90 (24%) of men >70yrs complied with criteria for active surveillance. CPC detection: 154/398 (39%) men <70yrs were CPC (+), specificity for cancer 86%, sensitivity 88%, 14/16 with a false (-) result had a small low grade PC. In men >70 years, 88/212 (42%) were CPC (+); specificity 92%, sensitivity 87%, 10/12 with a false (-) had small low grade tumours. False (+) results were more common in younger men 36/154 versus 10/88 (p<0.02). With a PSA cutoff of 6.5ng/ml, in men <70yrs, 108 PB would be avoided, missing 56 cancers of which 48 were clinically significant. Using CPC detection, 124 biopsies would be avoided, missing only 2 clinically significant cancers. In men >70 yrs using a PSA >6.5ng/ml would have resulted in 108 PB with 34 PC detected, of which 14(41%) were small low grade tumours. Conclusions: The use of CPC detection in the fit elderly significantly decreases the number of PBs without missing clinically significant cancers, indicating superiority to the use of age-related PSA.

Extended use of P504S Positive Primary Circulating Prostate Cell Detection to Determine the Need for Initial Prostate Biopsy in a Prostate Cancer Screening Program in Chile

Murray, Nigel P.,Reyes, Eduardo,Fuentealba, Cynthia,Jacob, Omar,Orellana, Nelson Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: To determine the frequency of primary circulating prostate cells (CPC) detection according to age and serum PSA levels in a cohort of men undergoing screening for prostate cancer and to determine the diagnostic yield in those men complying with the criteria for prostate biopsy. Materials and Methods: A prospective study was carried out to analyze all men evaluated in a hospital prostate cancer screening program. Primary CPCs were obtained by differential gel centrifugation and detected using standard immunocytochemistry using anti-PSA, positive samples undergoing a second process with anti-P504S. A malignant primary CPC was defined as PSA+ P504S+, and a test positive if 1 cell/4ml was detected. The frequency of primary CPC detection was compared with age and serum PSA levels. Men with a PSA >4.0ng/ml and/or abnormal rectal examination underwent 12 core prostate biopsy, and the results were registered as cancer/no-cancer and compared with the presence/absence of primary CPCs to calculate the diagnostic yield. Results: A total of 1,117 men participated; there was an association of primary CPC detection with increasing age and increasing serum PSA. Some 559 men underwent initial prostate biopsy of whom 207/559 (37.0%) were positive for primary CPCs and 183/559 (32.0%) had prostate cancer detected. The diagnostic yield of primary CPCs had a sensitivity of 88.5%, a specificity of 88.0%, and positive and negative predictive values of 78.3% and 94.9%, respectively. Conclusions: The use of primary CPCs for testing is recommended, since its high negative predictive value could be used to avoid prostate biopsy in men with an elevated PSA and/or abnormal DRE. Men positive for primary CPCs should undergo prostate biopsy. It is a test that could be implemented in the routine immunocytochemical laboratory.

Comparison of the Formula of PSA, Age, Prostate Volume and Race Versus PSA Density and the Detection of Primary Malignant Circulating Prostate Cells in Predicting a Positive Initial Prostate Biopsy in Chilean Men with Suspicion of Prostate Cancer

Murray, Nigel P,Reyes, Eduardo,Fuentealba, Cynthia,Orellana, Nelson,Morales, Francisca,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

Background: Combining risk factors for prostate cancer into a predictive tool may improve the detection of prostate cancer while decreasing the number of benign biopsies. We compare one such tool, age multiplied by prostate volume divided by total serum PSA (PSA-AV) with PSA density and detection of primary malignant circulating prostate cells (CPCs) in a Chilean prostate cancer screening program. The objectives were not only to determine the predictive values of each, but to determine the number of clinically significant cancers that would have been detected or missed. Materials and Methods: A prospective study was conducted of all men undergoing 12 core ultrasound guided prostate biopsy for suspicion of cancer attending the Hospital DIPRECA and Hospital de Carabineros de Chile. Total serum PSA was registered, prostate volumecalculated at the moment of biopsy, and an 8ml blood simple taken immediately before the biopsy procedure. Mononuclear cells were obtained from the blood simple using differential gel centrifugation and CPCs identified using immunocytchemistry with anti-PSA and anti-P504S. Biopsy results were classed as positive or negative for cancer and if positive the Gleason score, number of positive cores and percent infiltration recorded. Results: A total of 664 men participated, of whom 234 (35.2%) had cancer detected. They were older, had higher mean PSA, PSA density and lower PSA-AV. Detection of CPCs had high predictive score, sensitivity, sensibility and positive and negative predictive values, PSA-AV was not significantly different from PSA density in this population. The use of CPC detection avoided more biopsies and missed fewer significant cancers.Conclusions: In this screening population the use of CPC detection predicted the presence of clinically significant prostate cancer better than the other parameters. The high negative predictive value would allow men CPC negative to avoid biopsy but remain in follow up. The formula PSA-AV did not add to the predictive performance using PSA density.

Comparison between Use of PSA Kinetics and Bone Marrow Micrometastasis to Define Local or Systemic Relapse in Men with Biochemical Failure after Radical Prostatectomy for Prostate Cancer

Murray, Nigel P,Reyes, Eduardo,Fuentealba, Cynthia,Orellana, Nelson,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

Background: Treatment of biochemical failure after radical prostatectomy for prostate cancer is largely empirically based. The use of PSA kinetics has been used as a guide to determine local or systemic treatment of biochemical failure. We here compared PSA kinetics with detection of bone marrow micrometastasis as methods to determine local or systemic relapse. Materials and Methods: A transversal study was conducted of men with biochemical failure, defined as a serum PSA >0.2ng/ml after radical prostatectomy. Consecutive patients having undergone radical prostatectomy and with biochemical failure were enrolled and clinical and pathological details were recorded. Bone marrow biopsies were obtained from the iliac crest and touch prints made, micrometastasis (mM) being detected using anti-PSA. The clinical parameters of total serum PSA, PSA velocity, PSA doubling time and time to biochemical failure, age, Gleason score and pathological stage were registered. Results: A total of 147 men, mean age $71.6{\pm}8.2years$, with a median time to biochemical failure of 5.5 years (IQR 1.0-6.3 years) participated in the study. Bone marrow samples were positive for micrometastasis in 98/147 (67%) of patients at the time of biochemical failure. The results of bone marrow micrometastasis detected by immunocytochemistry were not concordant with local relapse as defined by PSA velocity, time to biochemical failure or Gleason score. In men with a PSA doubling time of < six months or a total serum PSA of >2,5ng/ml at the time of biochemical failure the detection of bone marrow micrometastasis was significantly higher. Conclusions: The detection of bone marrow micrometastasis could be useful in defining systemic relapse, this minimally invasive procedure warranting further studies with a larger group of patients.

Head to Head Comparison of the Chun Nomogram, Percentage Free PSA and Primary Circulating Prostate Cells to Predict the Presence of Prostate Cancer at Repeat Biopsy

Murray, Nigel P,Reyes, Eduardo,Orellana, Nelson,Fuentealba, Cynthia,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: The limitations of total serum PSA values remain problematic, especially after an initial negative prostate biopsy. In this prospective study of Chilean men with a continued suspicion of prostate cancer due to a persistently elevated total serum PSA, abnormal digital rectal examination and initial negative prostate biopsy were compared with the use of the on-line Chun nomagram, detection of primary malignant circulating prostate cells (CPCs) and free percent PSA to predict a positive second prostate biopsy. We hypothesized that men negative for circulating prostate cells have a small risk of clinically significant prostate cancer and thus may be conservatively observed. Men positive for circulating prostate cells should undergo biopsy to confirm prostate cancer. Materials and Methods: Consecutive men with a continued suspicion of prostate cancer underwent 12 core TRUS prostate biopsy; age, total serum PSA and percentage free PSA and Chun nomagram scores were registered. Immediately before biopsy an 8ml blood simple was taken to detect primary mCPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunostaining with anti-PSA and anti-P504S. Biopsies were classifed as cancer/no-cancer, mCPC detecton test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for percentage free PSA, Chun score and CPCs were calculated and compared. Diagnostic yields were calculated with reference to the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: A total of 164 men underwent a second biopsy; 41 (25%) had cancer; the AUCs were 0.65 for free PSA, 0.76 for the Chun score and 0.87 for CPC detection, the last having a significantly superior prediction value (p=0.01). Using cut off values of free PSA <10%, Chun score >50% and ${\geq}1$ CPC detected, CPC detection had a higher diagnostic yield. Some 4/41 cancers complied with the criteria for active surveillance, free PSA and the Chun score missed a higher number of significant cancers when compared with CPC detection. Conclusions: Primary CPC detection outperformed the use of free PSA and the Chun nomagram in predicting clinically significant prostate cancer at repeat prostate biopsy.

Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence

Murray, Nigel P,Reyes, Eduardo,Fuentealba, Cynthia,Jacob, Omar,Orellana, Nelson Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

Comparison of the Walz Nomogram and Presence of Secondary Circulating Prostate Cells for Predicting Early Biochemical Failure after Radical Prostatectomy for Prostate Cancer in Chilean Men

Murray, Nigel P,Reyes, Eduardo,Orellana, Nelson,Fuentealba, Cynthia,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Purpose: To determine the utility of secondary circulating prostate cells for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram. Materials and Methods: A single centre, prospective study of men with prostate cancer treated with radical prostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serum PSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differential gel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection. Results: A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure within two years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score ${\geq}8$, infiltration of seminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminative value for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher for circulating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of 75%. Conclusions: The nomagram had good predictive power to identify men with a high risk of biochemical failure within two years. The presence of circulating prostate cells had the same predictive power, with a higher sensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a group of men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk of early biochemical failure.