Transfusion Requirements After Cardiac Surgery The TRACS Randomized Controlled Trial

Context Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. Objective To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. Design, Setting, and Patients The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n=502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. Intervention Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit >= 30%) or to a restrictive strategy (hematocrit >= 24%). Main Outcome Measure Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). Results Hemoglobin concentrations were maintained at a mean of 10.5 g/dL(95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.09.2) in the restrictive-strategy group (P<.001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P<.001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P=.85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P=.002). Conclusion Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. Trial Registration clinicaltrials.gov Identifier: NCT01021631 JAMA. 2010; 304(14):1559-1567 www.jama.com

The prevalence of erectile dysfunction among Brazilian men screened for prostate cancer

OBJECTIVE To determine the prevalence of erectile dysfunction (ED) in a large cohort of Brazilian men who were screened for prostate cancer, and to determine risk factors in this population, as there are large cultural differences among countries in reporting the frequency of ED, and it is likely that the prevalence of ED among men screened for prostate cancer cannot be generally applied across countries. SUBJECTS AND METHODS The analysis focused on the baseline characteristics of 1008 consecutive South American men from Brazil with no known prostate disease who had routine screening for prostate cancer by urologists. The variables analysed were patient age, urinary symptoms, patient health-related quality of life (HRQL), prostate-specific antigen (PSA) levels, prostate volume and erectile function. To assess lower urinary tract symptoms (LUTS) and HRQL, we used the American Urological Association symptom score and its appended eighth question, respectively. Benign prostatic hyperplasia was defined as a prostate volume of > 30 g. Sexual function was assessed using the five-item version of the International Index of Erectile Function questionnaire. Thus, ED was considered to absent for scores of 22-25, mild for 17-21, mild to moderate for 12-16, moderate for 8-11, or severe for 5-7. Obesity was defined by calculating the body mass index (BMI), and categorized as underweight (< 18.5 kg/m

Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Context Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. Objectives To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. Design, Setting, and Participants We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. Main Outcome Measures The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. Results We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P=2.7 x 10(-4)) and/or with familial disease (5 of 20 samples; P=.005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P=.54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Conclusions Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein. JAMA. 2010;304(23):2611-2619 www.jama.com

Survival in Patients With Idiopathic, Familial, and Anorexigen-Associated Pulmonary Arterial Hypertension in the Modern Management Era

Background-Novel therapies have recently become available for pulmonary arterial hypertension. We conducted a study to characterize mortality in a multicenter prospective cohort of patients diagnosed with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension in the modern management era. Methods and Results-Between October 2002 and October 2003, 354 consecutive adult patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension (56 incident and 298 prevalent cases) were prospectively enrolled. Patients were followed up for 3 years, and survival rates were analyzed. For incident cases, estimated survival (95% confidence intervals [CIs]) at 1, 2, and 3 years was 85.7% (95% CI, 76.5 to 94.9), 69.6% (95% CI, 57.6 to 81.6), and 54.9% (95% CI, 41.8 to 68.0), respectively. In a combined analysis population (incident patients and prevalent patients diagnosed within 3 years before study entry; n = 190), 1-, 2-, and 3-year survival estimates were 82.9% (95% CI, 72.4 to 95.0), 67.1% (95% CI, 57.1 to 78.8), and 58.2% (95% CI, 49.0 to 69.3), respectively. Individual survival analysis identified the following as significantly and positively associated with survival: female gender, New York Heart Association functional class I/II, greater 6-minute walk distance, lower right atrial pressure, and higher cardiac output. Multivariable analysis showed that being female, having a greater 6-minute walk distance, and exhibiting higher cardiac output were jointly significantly associated with improved survival. Conclusions-In the modern management era, idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension remains a progressive, fatal disease. Mortality is most closely associated with male gender, right ventricular hemodynamic function, and exercise limitation. (Circulation. 2010; 122: 156-163.)

Muscle sympathetic nerve activity in patients with Chagas` disease

Background: The progression of heart failure in Chagas` disease has been explained by remodeling, leading to neurohumoral activation, or by the direct parasite damage to parasympathetic neurons during acute phase, leading to early sympathetic activation and progressive heart failure. To help distinguish between these hypotheses we studied muscle sympathetic nerve activity (MSNA) at rest and during handgrip exercise (30% of maximal voluntary contraction) in patients with Chagas` disease and normal ejection fraction vs. patients with heart failure. Methods: A consecutive study of 72 eligible out-patients/subjects was conducted between July 1998 and November 2004. The participants were classified in three advanced heart failure groups (New York Heart Association Functional Classes II-III): Chagas` disease (n-15), ischemic (n=15) and idiopathic cardiomyopathy (n-15). Twelve Chagas` disease patients without heart failure and normal ejection fraction, and 15 normal controls were also studied. MSNA was recorded directly from the peroneal nerve by microneurography technique. Results: MSNA was greater in heart failure patients when compared with Chagas` disease patients without heart failure (51 +/- 3 vs. 20 +/- 2 bursts/min P=0.0001). MSNA in Chagas` patients with normal ejection fraction and normal controls was not different. During exercise, MSNA was similar in all 3 heart failure groups. And, was lower in the Chagas` patients with normal ejection fraction than in patients with Chagas` disease and heart failure (28 +/- 1 vs. 63 +/- 5 bursts/min, respectively). Conclusion: MSNA is not elevated in patients with Chagas` disease with normal ejection fraction. These findings support the concept of remodeling and neurohumoral activation as a common pathway following significant cardiac injury. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial: study design and rationale

Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies. (Am Heart J 2009; 158:327-34.)

Prognostic value of left atrial volume in patients who underwent dobutamine stress echocardiography for known or suspected coronary artery disease

Background Left atrial volume indexed (LAVI) has been reported as a predictor of cardiovascular events. We sought to determine the prognostic value of LAVI for predicting the outcome of patients who underwent dobutamine stress echocardiography (DSE) for known or suspected coronary artery disease (CAD). Methods From January 2000 to July 2005, we studied 981 patients who underwent DSE and off-line measurements of LAVI. The value of DSE over clinical and LAVI data was examined using a stepwise log-rank test. Results During a median follow-up of 24 months, 56 (6%) events occurred. By univariate analysis, predictors of events were male sex, diabetes mellitus, previous myocardial infarction, left ventricular ejection fraction (LVEF), left atrial diameter indexed, LAVI, and abnormal DSE. By multivariate analysis, independent predictors were LVEF (relative risk [RR] = 0.98, 95% CI 0.95-1.00), LAVI (RR = 1.04, 95% CI 1.02-1.05), and abnormal DSE (RR = 2.70, 95% CI 1.28-5.69). In an incremental multivariate model, LAVI was additional to clinical data for predicting events (chi(2) 36.8, P < .001). The addition of DSE to clinical and LAVI yielded incremental information (chi(2) 55.3, P < .001). The 3-year event-free survival in patients with normal DSE and LAVI <= 33 mL/m(2) was 96%; with abnormal DSE and LAVI <= 33 mL/m(2), 91%; with normal DSE and LAVI >34 mL/m(2), 83%; and with abnormal DSE and LAVI >34 mL/m(2) 51%. Conclusion Left atrial volume indexed provides independent prognostic information in patients who underwent DSE for known or suspected CAD. Among patients with normal DSE, those with larger LAVI had worse outcome, and among patients with abnormal DSE, LAVI was still predictive. (Am Heart J 2008; 156:1110-6.)

Antigen Selection of Anti-DSG1 Autoantibodies During and Before the Onset of Endemic Pemphigus Foliaceus

Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is characterized by pathogenic anti-desmoglein 1 (DSG1) autoantibodies. To study the etiology of FS, hybridomas that secrete either IgM or IgG (predominantly IgG1 subclass) autoantibodies were generated from the B cells of eight FS patients and one individual 4 years before FS onset, and the H and L chain V genes of anti-DSG1 autoantibodies were analyzed. Multiple lines of evidence suggest that these anti-DSG1 autoantibodies are antigen selected. First, clonally related sets of anti-DSG1 hybridomas characterize the response in individual FS patients. Second, H and L chain V gene use seems to be biased, particularly among IgG hybridomas, and third, most hybridomas are mutants and exhibit a bias in favor of CDR (complementary determining region) amino acid replacement (R) mutations. Strikingly, pre-FS hybridomas also exhibit evidence of antigen selection, including an overlap in V(H) gene use and shared multiple R mutations with anti-DSG1 FS hybridomas, suggesting selection by the same or a similar antigen. We conclude that the anti-DSG1 response in FS is antigen driven and that selection for mutant anti-DSG1 B cells begins well before the onset of disease.

Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Endomyocardial Fibrosis Patients

Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54 +/- 12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.)

Endomyocardial fibrosis: pathological and molecular findings of surgically resected ventricular endomyocardium

Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown etiology prevalent in tropical regions affecting the inflow tract and apex of one or both ventricles, which show fibrous thickening of the endocardium and adjacent myocardium. Surgical treatment is recommended for patients in functional classes III or IV (New York Heart Association). The gross and histological features of the heart have been comprehensively studied in autopsies, but studies in surgical samples are still lacking. Histological and immunohistochemical features of EMF in surgical samples collected from 32 patients were described and correlated with clinical data. Polymerase chain reaction (PCR) and reverse transcription-PCR, performed on formalin fixed endomyocardial samples, were used retrospectively to detect genomes of certain cardiotropic viruses and Toxoplasma gondii. Ventricular endocardium was thickened by superficial acellular hyaline collagen fibers type I and III, with predominance of the former type. Besides fibrosis, a chronic inflammatory process and an anomalous lymphatic rich vascular pattern were observed in the deep endocardium, connected to the terminal coronary circulation of the myocardium, which might be an important pathological finding concerning EMF pathogenesis. Molecular analysis of the endomyocardium revealed high incidence of cardiotropic infective agents (6/12, 50%); however, their role in the disease pathogenesis is still controversial.

Lower N-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (1)H Magnetic Resonance Spectroscopy Study

Objective: The few studies applying single-voxel(1)H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. Method: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 +/- 2.9 years) and 38 healthy controls (79 female, mean age 13.9 +/- 2.7 years). We conducted multivoxel in vivo (1)H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. Results: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. Conclusions: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):85-94.

Influence of Modified Posterior Reconstruction of the Rhabdosphincter on Early Recovery of Continence and Anastomotic Leakage Rates after Robot-Assisted Radical Prostatectomy

Background: Posterior reconstruction (PR) of the rhabdosphincter has been previously described during retropubic radical prostatectomy, and shorter times to return of urinary continence were reported using this technical modification. This technique has also been applied during robot-assisted radical prostatectomy (RARP); however, contradictory results have been reported. Objective: We describe here a modified technique for PR of the rhabdosphincter during RARP and report its impact on early recovery of urinary continence and on cystographic leakage rates. Design, setting, and participants: We analyzed 803 consecutive patients who underwent RARP by a single surgeon over a 12-mo period: 330 without performing PR and 473 with PR. Surgical procedure: The reconstruction was performed using two 6-in 3-0 Poliglecaprone sutures tied together. The free edge of the remaining Denonvillier`s fascia was identified after prostatectomy and approximated to the posterior aspect of the rhabdosphincter and the posterior median raphe using one arm of the continuous suture. The second layer of the reconstruction was then performed with the other arm of the suture, approximating the posterior lip of the bladder neck and vesicoprostatic muscle to the posterior urethral edge. Measurements: Continence rates were assessed with a self-administrated, validated questionnaire (Expanded Prostate Cancer Index Composite) at 1, 4, 12, and 24 wk after catheter removal. Continence was defined as the use of ""no absorbent pads."" Cystogram was performed in all patients on postoperative day 4 or 5 before catheter removal. Results and limitations: There was no significant difference between the groups with respect to patient age, body mass index, prostate-specific antigen levels, prostate weight, American Urological Association symptom score, estimated blood loss, operative time, number of nerve-sparing procedures, and days with catheter. In the PR group, the continence rates at 1, 4, 12, and 24 wk postoperatively were 22.7%, 42.7%, 91.8%, and 96.3%, respectively; in the non-PR group, the continence rates were 28.7%, 51.6%, 91.1%, and 97%, respectively. The modified PR technique resulted in significantly higher continence rates at 1 and 4 wk after catheter removal (p = 0.048 and 0.016, respectively), although the continence rates at 12 and 24 wk were not significantly affected (p = 0.908 and p = 0.741, respectively). The median interval to recovery of continence was also statistically significantly shorter in the PR group (median: 4 wk; 95% confidence interval [CI]: 3.39-4.61) when compared to the non-PR group (median: 6 wk; 95% CI: 5.18-6.82; log-rank test, p = 0.037). Finally, the incidence of cystographic leaks was lower in the PR group (0.4% vs 2.1%; p = 0.036). Although the patients` baseline characteristics were similar between the groups, the patients were not preoperatively randomized and unknown confounding factors may have influenced the results. Conclusions: Our modified PR combines the benefits of early recovery of continence reported with the original PR technique with a reinforced watertight closure of the posterior anastomotic wall. Shorter interval to recovery of continence and lower incidence of cystographic leaks were demonstrated with our PR technique when compared to RARP with no reconstruction. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Morphology of the subgenual prefrontal cortex in pediatric bipolar disorder

Objectives The subgenual prefrontal cortex (SGPFC) is an important brain region involved in emotional regulation and reward mechanisms Volumetric abnormalities in this region have been identified in adults with bipolar disorder but thus far not in pediatric cases We examined the volume of this brain region in subjects with pediatric bipolar disorder (PBD) and compared them to healthy controls Methods Fifty one children and adolescents (mean age +/- SD 13 2 +/- 2 9 y) with DSM-IV PBD and 41 (mean age +/- SD 13 7 +/- 2 7 y) healthy comparison subjects (HC) underwent 1 5 T structural magnetic resonance imaging (MRI) brain scans We traced the SGPFC manually and compared SGPFC gray matter volumes using analysis of covariance with age gender and intracranial volume as covariates We also examined the relationship of family history of affective disorders and medication status to SGPFC volumes Results SGPFC volumes were not significantly different in PBD and HC subjects However exploratory analysis showed PBD subjects who had one or more first degree relatives with mood disorders (n = 33) had significantly smaller left hemisphere SGPFC compared to HC (p = 003 Sidak corrected) Current usage of a mood stabilizer was significantly associated with larger right SGPFC volume in PBD (F = 4 82 df = 1/41 p = 0 03) Conclusion Subjects with PBD and a close family history of mood disorders may have smaller left SGPFC volumes than HC Mood stabilizing medication may also impact SGPFC size and could have masked more subtle abnormalities overall (C) 2010 Elsevier Ltd All rights reserved

Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human USA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human USA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of USA have improved our understanding of the metabolic impact of USA, but further studies are needed before we can translate recent basic research findings to clinical practice. (C) 2010 Elsevier Ltd. All rights reserved.

Predictive Factors for Positive Surgical Margins and Their Locations After Robot-Assisted Laparoscopic Radical Prostatectomy

Background: Positive surgical margin (PSM) after radical prostatectomy (RP) has been shown to be an independent predictive factor for cancer recurrence. Several investigations have correlated clinical and histopathologic findings with surgical margin status after open RP. However, few studies have addressed the predictive factors for PSM after robot-assisted laparoscopic RP (RARP). Objective: We sought to identify predictive factors for PSMs and their locations after RARP. Design, setting, and participants: We prospectively analyzed 876 consecutive patients who underwent RARP from January 2008 to May 2009. Intervention: All patients underwent RARP performed by a single surgeon with previous experience of > 1500 cases. Measurements: Stepwise logistic regression was used to identify potential predictive factors for PSM. Three logistic regression models were built: (1) one using preoperative variables only, (2) another using all variables (preoperative, intraoperative, and postoperative) combined, and (3) one created to identify potential predictive factors for PSM location. Preoperative variables entered into the models included age, body mass index (BMI), prostate-specific antigen, clinical stage, number of positive cores, percentage of positive cores, and American Urological Association symptom score. Intra-and postoperative variables analyzed were type of nerve sparing, presence of median lobe, percentage of tumor in the surgical specimen, gland size, histopathologic findings, pathologic stage, and pathologic Gleason grade. Results and limitations: In the multivariable analysis including preoperative variables, clinical stage was the only independent predictive factor for PSM, with a higher PSM rate for T3 versus T1c (odds ratio [OR]: 10.7; 95% confidence interval [CI], 2.6-43.8) and for T2 versus T1c (OR: 2.9; 95% CI, 1.9-4.6). Considering pre-, intra-, and postoperative variables combined, percentage of tumor, pathologic stage, and pathologic Gleason score were associated with increased risk of PSM in the univariable analysis (p < 0.001 for all variables). However, in the multivariable analysis, pathologic stage (pT2 vs pT1; OR: 2.9; 95% CI, 1.9-4.6) and percentage of tumor in the surgical specimen (OR: 8.7; 95% CI, 2.2-34.5; p = 0.0022) were the only independent predictive factors for PSM. Finally, BMI was shown to be an independent predictive factor(OR: 1.1; 95% CI, 1.0-1.3; p = 0.0119) for apical PSMs, with increasing BMI predicting higher incidence of apex location. Because most of our patients were referred from other centers, the biopsy technique and the number of cores were not standardized in our series. Conclusions: Clinical stage was the only preoperative variable independently associated with PSM after RARP. Pathologic stage and percentage of tumor in the surgical specimen were identified as independent predictive factors for PSMs when analyzing pre-, intra-, and postoperative variables combined. BMI was shown to be an independent predictive factor for apical PSMs. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.