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2.
Am J Transplant ; 18(3): 632-641, 2018 03.
Article in English | MEDLINE | ID: mdl-29165871

ABSTRACT

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25-23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02-1.09, P < .01). However, there was not a significant association between CIT and all-cause graft failure (adjusted hazard ratio [aHR]: 1.01, 95% CI: 0.98-1.04, P = .4), death-censored graft failure ( [aHR]: 1.02, 95% CI, 0.98-1.06, P = .4), or mortality (aHR 1.00, 95% CI, 0.96-1.04, P > .9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.


Subject(s)
Cold Ischemia/adverse effects , Delayed Graft Function/etiology , Graft Rejection/etiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Living Donors , Tissue and Organ Harvesting/adverse effects , Travel/statistics & numerical data , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/mortality , Graft Survival , Humans , Kidney Function Tests , Male , Middle Aged , Organ Preservation , Prognosis , Risk Factors , Survival Rate , Time Factors , Tissue and Organ Procurement/methods , Transplant Recipients
3.
Urol Oncol ; 34(12): 529.e1-529.e7, 2016 12.
Article in English | MEDLINE | ID: mdl-27743849

ABSTRACT

INTRODUCTION: Postprostatectomy incontinence significantly impairs quality of life. Although bladder neck intussusception has been reported to accelerate urinary recovery after open radical retropubic prostatectomy, its adaption to robotic surgery has not been assessed. Accordingly, we describe our technique and compare outcomes between men treated with and without bladder neck intussusception during robot-assisted laparoscopic prostatectomy. MATERIALS AND METHODS: We performed a comparative trial of 48 men undergoing robot-assisted laparoscopic prostatectomy alternating between bladder neck intussusception (n = 24) and nonintussusception (n = 24). Intussusception was completed using 3-0 polyglycolic acid horizontal mattress sutures anterior and posterior to the bladder neck. We assessed baseline characteristics and clinicopathologic outcomes. Adjusting for age, body mass index, race, and D׳Amico risk classification, we prospectively compared urinary function at 2 days, 2 weeks, 2 months, and last follow-up using the urinary domain of the Expanded Prostate Cancer Index-Short Form. RESULTS: Baseline patient characteristics and clinicopathologic outcomes were similar between treatment groups (P>0.05). Median catheter duration (8 vs. 8d, P = 0.125) and rates of major postoperative complications (4.2% vs. 4.2%, P = 1.000) did not differ. In adjusted analyses, Expanded Prostate Cancer Index-Short Form urinary scores were significantly higher for the intussusception arm at 2 weeks (65.4 vs. 46.6, P = 0.019) before converging at 2 months (69.1 vs. 68.3, P = 0.929) after catheter removal and at last follow-up (median = 7mo, 80.5 vs. 77.0; P = 0.665). CONCLUSIONS: Bladder neck intussusception during robot-assisted laparoscopic prostatectomy is feasible and safe. Although the long-term effects appear limited, intussusception may improve urinary function during the early recovery period.


Subject(s)
Laparoscopy/methods , Postoperative Complications/prevention & control , Prostatectomy/methods , Robotics/methods , Suture Techniques , Urethra/surgery , Urinary Bladder/surgery , Urinary Incontinence/prevention & control , Aged , Body Mass Index , Humans , Lymph Node Excision , Male , Middle Aged , Prostatic Neoplasms/surgery , Treatment Outcome , Urinary Incontinence/etiology
4.
J Am Coll Surg ; 222(5): 798-804, 2016 05.
Article in English | MEDLINE | ID: mdl-27016901

ABSTRACT

BACKGROUND: Delay in the return of bowel function often prolongs hospitalization after kidney transplantation, leading to increased patient morbidity and health care costs. Polyethylene glycol (PEG) solution has been observed to aid the return of bowel function in postoperative patients undergoing abdominal surgery. STUDY DESIGN: Using a 2-arm, single-surgeon, nonrandomized study, we compared the addition of PEG along with early resumption of diet with a control group using only early resumption of diet in kidney transplantation patients. RESULTS: There were 51 subjects in the control group and 47 subjects in the PEG intervention group. The primary outcomes measure, time to bowel movement, was significantly shorter than the control group by an entire day (2.9 ± 1.1 days vs 4.0 ± 1.3 days; p < 0.001). In propensity score analysis, patients receiving PEG had bowel movements sooner (-1.06 ± 0.25 days; p < 0.001) and decreased lengths of stay (-1.16 ± 0.27 days; p < 0.001). CONCLUSIONS: Polyethylene glycol significantly reduced time to return of bowel function and postoperative length of stay. By adding PEG to the postoperative protocol, we can help to reduce costs of hospitalization and improve overall outcomes in renal transplantation patients.


Subject(s)
Defecation/drug effects , Intestinal Pseudo-Obstruction/drug therapy , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Polyethylene Glycols/administration & dosage , Surface-Active Agents/administration & dosage , Adult , Clinical Protocols , Electrolytes/administration & dosage , Female , Humans , Intestinal Pseudo-Obstruction/etiology , Intestinal Pseudo-Obstruction/prevention & control , Length of Stay , Male , Middle Aged
5.
Transplantation ; 99(7): 1410-5, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25606799

ABSTRACT

BACKGROUND: Although kidney paired donation (KPD) has led to thousands of transplants, the 2012 KPD Consensus Conference concluded that more could be done. Perceptions are that a large number of match offers never resulted in transplantations, and unfruitful matches have both financial and emotional costs. METHODS: To describe, quantify, and analyze the unrealized match offers, we studied the matching process from registration to transplantation in the National Kidney Registry, a large KPD registry, over a 25-month period. RESULTS: Of the 3,180 match offers, 454 were turned down. The most common reasons were the donor was not acceptable (50%) and their recipient had unacceptably high donor-specific antibodies (28%). Of the 2,228 accepted offers, 1,335 advanced to the cell-based cross-match stage because 893 of these were part of chains that fell through. Fifty-five of 887 recorded cell-based cross-matches were positive, 20 donors were unacceptable, and 22 recipients had unacceptably high donor-specific antibodies. Six hundred ninety transplantations were performed. CONCLUSION: Despite the success of KPD, by analyzing the matching process, we identify several strategies to increase the number of KPD transplantations, including recruiting more participants, processing the match offers more quickly at the transplant center level, enhancing the donor preselection tools, improving communication between centers and the registries, and combining desensitization with KPD.


Subject(s)
Directed Tissue Donation , Kidney Transplantation/methods , Living Donors/supply & distribution , Process Assessment, Health Care , Tissue and Organ Procurement , Donor Selection , HLA Antigens/blood , Histocompatibility , Histocompatibility Testing , Humans , Isoantibodies/blood , Kidney Transplantation/adverse effects , Registries , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States
6.
Urology ; 85(1): 107-12, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25530372

ABSTRACT

OBJECTIVE: To describe and illustrate the evolution of surgical technique, emphasizing technical modifications of laparoscopic donor nephrectomy (LDN) and the impact on complication outcome. METHODS: This is a retrospective observational study of prospectively collected data on all consecutive purely LDN surgeries performed at a tertiary academic medical center (n = 1325), performed between March 2000 and October 2013. RESULTS: Over time, LDN was performed on older patients, changing from a mean of 35.7 years in 2000 to 41.2 years in 2013 (P <.001). Additionally, mean blood loss decreased from 75 mL in 2000 to 21.6 mL in 2013 (P <.001). However, body mass index, operative time, and length of stay remained similar. Overall, there were 105 (7.9%) complications: Clavien grade 1 (n = 81, 6.1%) and grade 2 or higher (n = 23, 1.8%). Procedure duration, blood loss, surgeon, year of procedure, laterality, body mass index, age, and gender did not significantly predict complications. There was no significant difference for Clavien complication rates between the early learning period (first 150 cases) and the rest of the series. CONCLUSION: With continual refinement with LDN techniques based on intraoperative observations and technological advances, complication rates remain consistently low, despite increasing donor age.


Subject(s)
Laparoscopy , Nephrectomy/methods , Tissue and Organ Harvesting , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nephrectomy/adverse effects , Retrospective Studies , Tissue Donors , Young Adult
7.
Transpl Int ; 27(11): 1175-82, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25052215

ABSTRACT

The disparity between kidney transplant candidates and donors necessitates innovations to increase organ availability. Transporting kidneys allows for living donors and recipients to undergo surgery with a familiar transplant team, city, friends, and family. The effect of shipping kidneys and prolonged cold ischemia time (CIT) with living donor transplantation outcomes is not clearly known. This retrospective matched (age, gender, race, and year of procedure) cohort study compared allograft outcomes for shipped live donor kidney transplants and nonshipped living donor kidney transplants. Fifty-seven shipped live donor kidneys were transplanted from 31 institutions in 26 cities. The mean shipping distance was 1634 miles (range 123-2811) with mean CIT of 12.1 ± 2.8 h. The incidence of delayed graft function in the shipped cohort was 1.8% (1/57) compared to 0% (0/57) in the nonshipped cohort. The 1-year allograft survival was 98% in both cohorts. There were no significant differences between the mean serum creatinine values or the rates of serum creatinine decline in the immediate postoperative period even after adjusted for gender and differences in recipient and donor BMI. Despite prolonged CITs, outcomes for shipped live donor kidney transplants were similar when compared to matched nonshipped living donor kidney transplants.


Subject(s)
Kidney Transplantation , Living Donors , Tissue and Organ Procurement , Adult , Cohort Studies , Cold Ischemia , Creatinine/blood , Delayed Graft Function , Female , Graft Survival , Humans , Male , Middle Aged , Retrospective Studies , Transportation , Unrelated Donors
8.
Eur Urol ; 66(3): 542-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24857539

ABSTRACT

BACKGROUND: Robot-assisted retroperitoneoscopic partial nephrectomy (RARPN) may be used for posterior renal masses or with prior abdominal surgery; however, there is relatively less familiarity with RARPN. OBJECTIVE: To demonstrate RARPN technique and outcomes. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study of 227 consecutive RARPNs was performed at the Swedish Medical Center, the University of Michigan, and the University of California, Los Angeles, from 2006 to 2013. SURGICAL PROCEDURE: RARPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed positive margins and cancer recurrence. Stepwise regression was used to examine factors associated with complications, estimated blood loss (EBL), warm ischemia time (WIT), operative time (OT), and length of stay (LOS). RESULTS AND LIMITATIONS: The median age was 60 yr (interquartile range [IQR]: 52-66), and the median body mass index (BMI) was 28.2 kg/m(2) (IQR: 25.6-32.6). Median maximum tumor diameter was 2.3 cm (IQR: 1.7-3.1). Median OT and WIT were 165 min (IQR: 134-200) and 19 min (IQR: 16-24), respectively; median EBL was 75 ml (IQR: 50-150), and median LOS was 2 d (IQR: 1-3). Twenty-eight subjects (12.3%) experienced complications, three (1.3%) had urine leaks, and three (1.3%) had pseudoaneurysms that required reintervention. There was one conversion to radical nephrectomy and three transfusions. Overall, 143 clear cell carcinomas (62.6%) composed most of the histology with eight positive margins (3.5%) and two recurrences (0.9%) with a median follow-up of 2.7 yr. In adjusted analyses, intersurgeon variation was associated with complications (odds ratio [OR]: 3.66; 95% confidence interval, 1.31-10.27; p = 0.014) and WIT (parameter estimate [PE; plus or minus standard error]: 4.84 ± 2.14; p = 0.025). Higher surgeon volume was associated with shorter WIT (PE: -0.06 ± 0.02; p = 0.002). Higher BMI was associated with longer OT (PE: 2.09 ± 0.56; p < 0.001). Longer OT was associated with longer LOS (PE: 0.01 ± 0.01; p = 0.002). Finally, there was a trend for intersurgeon variation in OT (PE: 18.5 ± 10.3; p = 0.075). CONCLUSIONS: RARPN has acceptable morbidity and oncologic outcomes, despite intersurgeon variation in WIT and complications. Greater experience is associated with shorter WIT. PATIENT SUMMARY: Robot-assisted retroperitoneoscopic partial nephrectomy has acceptable morbidity and oncologic outcomes, and there is intersurgeon variation in warm ischemia time and complications.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Laparoscopy/methods , Neoplasm Recurrence, Local/etiology , Nephrectomy/methods , Robotic Surgical Procedures/methods , Aged , Blood Loss, Surgical , Body Mass Index , Carcinoma, Renal Cell/pathology , Clinical Competence , Female , Follow-Up Studies , Humans , Kidney Neoplasms/pathology , Laparoscopy/adverse effects , Length of Stay , Male , Middle Aged , Neoplasm, Residual , Nephrectomy/adverse effects , Operative Time , Retroperitoneal Space , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Treatment Outcome , Warm Ischemia
9.
Eur Urol ; 65(3): 659-64, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24139942

ABSTRACT

BACKGROUND: Pure laparoscopic donor nephrectomy (LDN) is a unique intervention because it carries known risks and complications, yet carries no direct benefit to the donor. Therefore, it is critical to continually examine and improve quality of care. OBJECTIVE: To identify factors affecting LDN outcomes and complications. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of prospectively collected data for 1204 consecutive LDNs performed from March 2000 through August 2012. INTERVENTION: LDN performed at an academic training center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable regression, we assessed the effect of age, sex, body mass index (BMI), laterality, and vascular variation on operative time, estimated blood loss (EBL), complications, and length of stay. RESULTS AND LIMITATIONS: The following variables were associated with longer operative time (data given as parameter estimate plus or minus the standard error): female sex (9.09 ± 2.43; p<0.001), higher BMI (1.03 ± 0.32; p=0.001), two (7.87 ± 2.70; p=0.004) and three or more (22.45 ± 7.13; p=0.002) versus one renal artery, and early renal arterial branching (5.67 ± 2.82; p=0.045), while early renal arterial branching (7.81 ± 3.85; p=0.043) was associated with higher EBL. Overall, 8.2% of LDNs experienced complications, and by modified Clavien classification, 74 (5.9%) were grade 1, 13 (1.1%) were grade 2a, 10 (0.8%) were grade 2b, and 2 (0.2%) were grade 2c. There were no grade 3 or 4 complications. Three or more renal arteries (odds ratio [OR]: 2.74; 95% CI, 1.05-7.16; p=0.04) and late renal vein confluence (OR: 2.42; 95% CI, 1.50-3.91; p=0.0003) were associated with more complications. Finally, we did not find an association of the independent variables with length of stay. A limitation is that warm ischemia time was not assessed. CONCLUSIONS: In our series, renal vascular variation prolonged operative time and was associated with more complications. While complicated donor anatomy is not a contraindication of LDN, surgical decision-making should take into consideration these results.


Subject(s)
Laparoscopy , Living Donors , Nephrectomy/adverse effects , Nephrectomy/methods , Tissue and Organ Harvesting/adverse effects , Tissue and Organ Harvesting/methods , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Retrospective Studies , Treatment Outcome , Young Adult
10.
BJU Int ; 109(11): 1600-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22221668

ABSTRACT

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sarcomatoid renal cell carcinoma can occur in the setting of all histological subtypes of kidney cancer. These tumours are very aggressive and many patients present with disseminated disease. Long-term survival is poor and the durable responses to systemic therapy are infrequent. Our large cohort analyses the influence of pathological tumour characteristics in determining prognosis for patients with sarcomatoid renal cell carcinoma undergoing surgical resection. This series helps define the prognostic influence of histological subtype, type of sarcomatoid morphology, the percentage necrosis and sarcomatoid features, and the presence of microvascular invasion. OBJECTIVES: To examine the influence of pathological tumour characteristics on survival to aid prognostication and clinical trial design. Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have poor prognosis and response to systemic therapy. PATIENTS AND METHODS: A single-centre database was reviewed to identify all patients with sRCC. Clinical variables and pathological information, including histology, necrosis, percentage of sarcomatoid features (PSF) and microvascular invasion (MVI), were recorded and correlated to outcome. RESULTS: Analyses of 104 patients with sRCC found that the median (range) size of tumours was 9.5 cm (2.5-30), 65% of patients had areas of clear cell histology, and 69.2% had metastatic disease at presentation. The PSF did not influence tumour size, stage, necrosis, MVI, nodes or metastasis. A total of 85 patients (81.7%) died during the follow-up period with a median (95% confidence interval [CI]) survival of 5.9 months (4.7-8.9). In the overall cohort, Eastern Cooperative Group performance status (ECOGPS), tumour size and metastatic disease were independent predictors of poor survival. MVI, PSF and percentage necrosis were strongly associated with outcome but were not independent predictors of outcome. A multivariate risk model was established that incorporated six covariates (tumour size, MVI, ECOGPS, PSF, necrosis, and metastatic disease) to produce a predictive tool. CONCLUSIONS: Both patients with localized and metastatic sRCC have very poor survival outcomes. Pathological features MVI, PSF and necrosis are important predictors of survival and could be used in a prognostic model while grade and histology do not influence prognosis. A prognostic model, if validated, could aid in patient counselling and/or clinical trial design.


Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Aged , Carcinoma, Renal Cell/therapy , Cohort Studies , Female , Humans , Kidney Neoplasms/therapy , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Nephrectomy , Prognosis , Survival Rate
11.
Prostate ; 70(13): 1471-9, 2010 Sep 15.
Article in English | MEDLINE | ID: mdl-20687220

ABSTRACT

BACKGROUND: Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. METHODS: Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. RESULTS: Compared to TC in normal prostate samples (n = 54; TC mean = 0.98), tumor samples displayed telomere attrition (n = 45; TC mean = 0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n = 73; TC mean = 0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n = 128; TC mean = 1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. CONCLUSIONS: Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer.


Subject(s)
Adenocarcinoma/pathology , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Telomere/pathology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adult , Aged , Analysis of Variance , Humans , Male , Middle Aged , Prostate/metabolism , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Telomere/metabolism
12.
BJU Int ; 105(7): 940-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19888984

ABSTRACT

OBJECTIVE: To prospectively determine the accuracy of 14-, 18- and 20-G core needle biopsies to render the appropriate histological diagnosis of solid, enhancing renal masses, using a controlled, ex-vivo biopsy technique. PATIENTS AND METHODS: From March 2007 to September 2007, 31 patients undergoing partial or radical nephrectomy were randomly selected for biopsy. After extirpative surgery, three ex-vivo biopsies were taken from each lesion with 14-, 18- and 20-G biopsy needles. One experienced genitourinary pathologist, unaware of patient identifiers and final pathology results, determined the biopsy histology and tumour grade, based on standard haematoxylin and eosin (H&E) techniques and immunohistochemistry. RESULTS: The final pathological evaluation classified 21 masses (68%) as clear cell renal cell carcinoma (RCC), three (10%) as papillary RCC, three (10%) as chromophobe RCC, three (10%) as oncocytoma and one (3%) as a benign lymphoid infiltrate. The biopsy histology correlated with the final pathology in 29/31 cases (94%) with the 14-G, 30/31 cases (97%) with the 18-G and 25/31 cases (81%) with the 20-G needles. In two cases chromophobe RCC was misdiagnosed with oncocytoma, and vice versa. CONCLUSION: In this study a minimum of an 18-G biopsy needle was the most accurate in determining the histological diagnosis. Clear cell and papillary RCCs were accurately diagnosed on biopsy using an 18-G, whereas oncocytoma and chromophobe RCC were difficult to differentiate using standard H&E techniques and immunohistochemistry.


Subject(s)
Adenoma, Oxyphilic/pathology , Biopsy, Needle/standards , Carcinoma, Papillary/pathology , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Nephrectomy/methods , Adult , Aged , Biopsy, Needle/instrumentation , Carcinoma, Papillary/surgery , Carcinoma, Renal Cell/surgery , Epidemiologic Methods , Female , Humans , Immunohistochemistry , Kidney Neoplasms/surgery , Male , Middle Aged , Needles/standards , Young Adult
13.
Urology ; 75(3): 724-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19615720

ABSTRACT

OBJECTIVE: To determine whether measurement of telomere DNA content (TC) in prostate biopsy tissue predicts prostate-specific antigen (PSA) recurrence in men after undergoing radical prostatectomy for prostate cancer. METHODS: Slot blot titration assay was used to quantitate TC in archived diagnostic prostate needle biopsy specimens for subjects (n = 103) diagnosed with prostate cancer and who subsequently underwent radical prostatectomy between 1993 and 1997. TC was compared to the clinical outcome measure; PSA recurrence, defined as an increase in PSA > or = 0.2 ng/mL on 2 or more consecutive measurements post-prostatectomy, was observed retrospectively, for a mean follow-up period of 114 months (range, 1-165). RESULTS: In the cohort, 46 subjects had a PSA recurrence. In a univariate Cox proportional hazards model, low TC (< 0.3 of standard) demonstrated a significant risk for PSA recurrence (HR = 1.94; 95% CI: 1.02-3.69, P = .04). In a subset analysis of men with biopsy Gleason sum < or = 6 (n = 63; 25 recurrences), a univariate Cox proportional hazards model demonstrated that low TC had a greater risk of PSA recurrence (HR = 4.53; 95% CI: 2.00-10.2, P < .01). In a multivariate Cox proportional hazards model, low TC was also significantly associated with PSA recurrence in this subset after controlling for preoperative PSA levels (HR = 6.62; 95% CI: 2.69-16.3, P < .01). CONCLUSIONS: Low TC measured in prostate biopsy tissue predicts early likelihood of post-prostatectomy PSA recurrence in a retrospective analysis, and in men with biopsy Gleason sum < or = 6 disease it is also independent of preoperative PSA level.


Subject(s)
DNA/analysis , Prostate-Specific Antigen/blood , Prostate/chemistry , Prostate/pathology , Prostatectomy , Prostatic Neoplasms/surgery , Telomere/genetics , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Predictive Value of Tests , Prostatic Neoplasms/blood , Retrospective Studies , Time Factors
14.
Prostate ; 68(16): 1798-805, 2008 Dec 01.
Article in English | MEDLINE | ID: mdl-18780294

ABSTRACT

BACKGROUND: Emerging evidence indicates that testosterone (T), and not dihydrotestosterone (DHT), is the most relevant androgen that promotes carcinogenesis in the prostate. Steroid 5-alpha reductase type II (SRD5A2) catalyzes the irreversible conversion of T to DHT in male reproductive organs. Because the SRD5A2 gene is highly polymorphic at codon 89, two SRD5A2 isoforms are expressed that differ in K(m) and V(max) values. The more common and rapid catalytic isoform contains a valine residue at position 89; the slower-catalytic variant contains leucine at this position. METHODS: Thirty-three men with early onset prostate cancer (PCa) were genotyped for the SRD5A2 V89L substitution and other polymorphisms in genes encoding receptors or enzymes that play important roles in pathways of steroid metabolism to ascertain if they were associated with standard clinical measures of disease progression at the time of diagnosis. RESULTS: The expression of at least one SRD5A2 leucine allele in young men with PCa was associated with more significant disease at the time of presentation, as was defined by pretreatment PSA level, clinical staging and Gleason score when compared with affected subjects harboring the more common SRD5A2 valine variant. A dosage effect of a single leucine allele was evident in heterozygotes, as values of their clinical and pathological variables were consistently situated between the extremes of the homozygous V or L phenotypes. CONCLUSION: The SRD5A2 leucine isoform appears to be acting in a dose-dependent manner as a significant disease-modifying factor in young men diagnosed with PCa.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Adenocarcinoma/genetics , Polymorphism, Single Nucleotide/genetics , Prostatic Neoplasms/genetics , Severity of Illness Index , Age of Onset , Aged , Aged, 80 and over , Case-Control Studies , Disease Progression , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Middle Aged , Pilot Projects , Risk Factors
15.
J Urol ; 176(5): 2274-9, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17070311

ABSTRACT

PURPOSE: We compared the performance of citrate concentration measurements in unprocessed human semen and expressed prostatic secretions from controls and from patients with biopsy confirmed prostate cancer to that of prostate specific antigen testing with respect to specificity and sensitivity for prostate cancer detection. MATERIALS AND METHODS: Semen and expressed prostatic secretions were collected in biopsy proven, prostate cancer bearing and noncancer bearing cases. Citrate concentrations were determined by quantitative in vitro, high field, water suppressed proton nuclear magnetic resonance spectroscopy. Assessments of the diagnostic performance of citrate and prostate specific antigen results in our study populations were made by ROC curve analysis. RESULTS: Citrate was measured in samples from 61 participants, of whom 16 without and 21 with cancer donated semen, and 17 without and 7 with cancer donated expressed prostatic secretions. Mean citrate +/- SE compared to that in controls was 2.7-fold lower in patients with cancer samples in semen (132.2 +/- 30.1 vs 48.0 +/- 7.9 mM, p < 0.05) and expressed prostatic secretions (221.4 +/- 55.4 vs 81.5 +/- 36.0 mM, p < 0.05). ROC curve analysis showed that measurements of citrate in semen performed as well as measurements of citrate in expressed prostatic secretion for detecting prostate cancer (AUC 0.81, 95% CI 0.60 to 0.92 and AUC 0.73, 95% CI 0.38 to 0.90, respectively, p > 0.05). ROC curve analysis also showed that the measurement of citrate in either fluid outperformed prostate specific antigen measurement for detecting prostate cancer in these subjects (AUC 0.61, 95% CI 0.44 to 0.74). CONCLUSIONS: In vitro nuclear magnetic resonance spectroscopic measurement of the citrate concentration in semen or expressed prostatic secretions outperforms prostate specific antigen testing for detecting prostate cancer.


Subject(s)
Body Fluids/chemistry , Citric Acid/analysis , Magnetic Resonance Spectroscopy , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/diagnosis , Semen/chemistry , Aged , Humans , Male , Middle Aged , Prostate
16.
J Interv Card Electrophysiol ; 12(3): 213-20, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15875112

ABSTRACT

OBJECTIVE: We evaluated the prevalence, trends, outcomes and the general experience of physicians performing atrial fibrillation ablation (AF-ABL) in the United States (US). BACKGROUND: AF-ABL is a non-pharmacological and potentially curative therapy for AF. Success rates for AF-ABL have been reported to be between 80 and 90%. Although there are numerous clinical trial addressing this therapy little is known about the general status of AF-ABL in clinical practice. METHODS: We administered a mailed survey to the physician members of a professional arrhythmia society (Heart Rhythm Society, formerly known as the North American Society of Pacing and Electrophysiology) who practiced in the US (n = 1843). RESULTS: There were 304 responses, 66% (n = 204) performed ABL and 30% (n = 92) performed AF-ABL. The study group performed a total of 5,592 AF-ABL from 2000 to 2003, out of 72,575 total ABL procedures during the same time period. There was a four-fold increase in the number of AF-ABL between 2000 and 2003 (2000: 628 vs. 2003: 2,575). In the same period, the self-reported short and long-term success rates of AF-ABL improved an average of 18 +/- 4% (p < or = 0.001). In 2003 the average self-reported one-month, one-year, and two-year success rates were: 71 +/- 4%, 66 +/- 5%, 63 +/- 6% respectively. The predicted five-year success was 60 +/- 4%. The average procedure took 4.5 +/- 0.4 hours. Physicians reported that approximately 29 +/- 4% of their patents were potential candidates for AF-ABL. CONCLUSIONS: AF-ABL is becoming a much more common procedure in the US. Over the last four years the perceived short and long term success rates of AF-ABL have improved. Success rates in this survey are 10 to 20% lower than those reported in the recent clinical trials.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/trends , Outcome Assessment, Health Care , Practice Patterns, Physicians'/statistics & numerical data , Analysis of Variance , Atrial Fibrillation/epidemiology , Humans , Prevalence , Regression Analysis , Surveys and Questionnaires , United States/epidemiology
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