Faculty Bibliography

Retraction of the bowels during abdominal surgery is generally facilitated by the use of a combination of various retractors along with surgical towels or sponges. The use of surgical towels and sponges may lead to retained foreign bodies or adhesions. In addition, these towels and sponges often require manipulation during long surgical procedures. The ideal way to avoid these problems in abdominal surgery is to develop a technique for retraction of the abdominal contents that eliminates the requirement for these foreign bodies. This article presents the results of a small trial for Lap Pak (Seguro Surgical, Columbia, MD), a disposable radio-opaque device that is made of silicone and retracts the bowels in a cephalad orientation without the need for towels or sponges.

BACKGROUND: Measurement of prostate-specific antigen (PSA) in prostate cancer patients following radical prostatectomy (RP) has been hindered by the limit of quantification of available assays. Because radical prostatectomy removes the tissue responsible for PSA production, postsurgical PSA is typically undetectable with current assay methods. Evidence suggests, however, that more sensitive determination of PSA status following RP could improve assessment of patient prognosis and response to treatment and better target secondary therapy for those who may benefit most. We developed an investigational digital immunoassay with a limit of quantification 2 logs lower than current ultrasensitive third-generation PSA assays. METHODS: We developed reagents for a bead-based ELISA for use with high-density arrays of femtoliter-volume wells. Anti-PSA capture beads with immunocomplexes and associated enzyme labels were singulated within the wells of the arrays and interrogated for the presence of enzymatic product. We characterized analytical performance, compared its accuracy with a commercially available test, and analyzed longitudinal serum samples from a pilot study of 33 RP patients. RESULTS: The assay exhibited a functional sensitivity (20% interassay CV) <0.05 pg/mL, total imprecision <10% from 1 to 50 pg/mL, and excellent agreement with the comparator method. All RP samples were well within the assay measurement capability. PSA concentrations following surgery were found to be predictive of prostate cancer recurrence risk over 5 years. CONCLUSIONS: The robust 2-log improvement in limit of quantification relative to current ultrasensitive assays and the validated analytical performance of the assay allow for accurate assessment of PSA status after RP

Study Type - Harm (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Erythropoletin-stimulating agents (ESAs) have been widely prescribed for treating anaemia secondary to advanced maligancies with the objective of reducing the need for red blood cell transfusions and improving the quality of life. However, the risk/benefit of ESAs has recently been questioned and metaanalyses showing that these agents are associated with an increased risk of mortality when chronically administered to patients with advanced/metastatic cancers. In this study we examined the impact of short-term preoperative utilization of ESAs on biochemical recurrence - free survival rates after open radical retropubic prostatectomy (ORRP). OBJECTIVE: * To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival. PATIENTS AND METHODS: * From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. * Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). * Patients were also classified as having low-, intermediate- or high-risk disease based on D'Amico risk categories. * Kaplan-Meier survival curves and Cox's proportional hazard models were used to estimate BCR-free survival by ESA treatment. RESULTS: * A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. * There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. * In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups. CONCLUSIONS: * The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. * The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease

BACKGROUND: Prostate-specific antigen (PSA) is the only independent predictor of biochemical recurrence (BCR) following radical prostatectomy (RP) subject to change over time. OBJECTIVE: To determine whether an ultrasensitive PSA measured at 3 yr following RP is a predictor of subsequent BCR. DESIGN, SETTING, AND PARTICIPANTS: There were 1197 consecutive men with clinically localized prostate cancer who underwent an open radical retropubic prostatectomy (ORRP) at a tertiary referral academic medical center. Exclusions included 107 men (8.9%) who developed a PSA level >/=0.2 ng/ml or underwent hormone therapy or radiation therapy (RT) within the first 3 r after surgery, 191 men (16%) who did not undergo a 3-yr ultrasensitive PSA assay, and 98 men (8.2%) who had PSA levels >/=0.1 and <0.2 at 3 yr. The remaining 801 men were stratified into two groups based on their ultrasensitive PSA level at 3 yr postoperatively: group 1, which consisted of patients whose PSA was </=0.04 (n=765), and group 2, which consisted of patients whose PSA was >0.04 and <0.10 (n=36). MEASUREMENTS: Delayed BCR was the primary end point and represented those men in this cohort who developed a PSA level >/=0.2 or underwent salvage RT for a persistently rising PSA level after 3 yr of follow-up. RESULTS AND LIMITATIONS: The 7-yr cumulative BCR-free survival rate for groups 1 and 2 was 0.957 (95% confidence interval [CI], 0.920-0.978) and 0.654 (95% CI, 0.318-0.855), respectively. In multivariable Cox proportional hazards models, ultrasensitive PSA level at 3 yr remained the only significant predictor of delayed BCR (likelihood ratio chi(2) for full model: 27.03; df=1; p < 0.001). A limitation of the study is that no uniform PSA assay was obtained. CONCLUSIONS: Our findings provide compelling evidence that an ultrasensitive PSA at 3 yr following RP provides useful insights into delayed BCR and is a source of reassurance for the overwhelming majority of men being followed for delayed recurrences

The optimal management of men with very favorable clinicopathological factors who develop biochemical recurrence (BCR) after radical prostatectomy (RP) has not been previously reported. Both local and systemic recurrences are unlikely in this cohort. This study examines their management and outcomes. Between October 2000 to March 2010, 1627 men underwent open RP by a single surgeon. In all, 448 (27.5%) met the following criteria for extremely low risk disease: preoperative PSA level <10 ng ml(-1), clinical stage T1c/T2a, Gleason score </=6, estimated cancer volume in the surgical specimen </=5% and no evidence for positive surgical margin. Undetectable PSA was defined as </=0.04 ng ml(-1). BCR was defined as PSA >/=0.2 ng ml(-1) or initiation of salvage radiation therapy (SRT) for progressively rising PSA. At 54 months mean follow-up (range 3-114 months), 9 (2%) of the 448 men developed BCR. Mean time to BCR was 63 months (range 12-93) and mean PSA doubling time was 15 months (range 6-27). Six underwent SRT, two elected surveillance and one was lost to follow-up. All men undergoing SRT exhibited more than 75% reduction in pre-SRT PSA, indicating the presence of local disease recurrence. All men undergoing SRT maintained PSA levels <0.1 at last follow-up. The BCR of 2% confirmed that we selected a cohort with extremely low risk for BCR after RP. We demonstrated that men fulfilling our criteria who develop BCR all harbor local disease based on favorable response to SRT. These men should be managed with SRT if recurrence is felt to be biologically significant

PURPOSE: The prevalence and mechanism of incontinence during sexual activity after radical prostatectomy has not been well described. We determined the prevalence and severity of incontinence during sexual activity with time and the relationship between incontinence during sexual activity and stress urinary incontinence in the absence of sexual activity. MATERIALS AND METHODS: A total of 1,459 men with prostate cancer underwent radical prostatectomy between October 2000 and December 2007, as performed by 1 surgeon. Patients completed UCLA-PCI preoperatively, and 3, 6, 12 and 24 months postoperatively. We analyzed the frequency distribution of incontinence during sexual activity and stress urinary incontinence with time. We also examined the relationship between incontinence during sexual activity and stress urinary incontinence by chi-square analysis. RESULTS: The percent of patients who reported any bother from incontinence during sexual activity was 44.4% at 3 months, which decreased to 36.1% at 24 months. The percent of patients reporting major bother from incontinence during sexual activity was 22.4% and 12.1% at 3 and 24 months, respectively. Bother from incontinence during sexual activity and from stress urinary incontinence were strongly associated at all times (p <0.001). More than half of the men with major bother due to incontinence during sexual activity also reported bother from stress urinary incontinence. However, more than 10% of those with no stress urinary incontinence problem reported major bother from incontinence during sexual activity. CONCLUSIONS: Incontinence during sexual activity is a persistent problem for some men after radical prostatectomy. Significant incontinence during sexual activity may occur in the absence of stress urinary incontinence during nonsexual activities. Effective management of this problem requires further investigation

We have shown previously that during branching morphogenesis of the mouse prostate gland, Bone morphogenetic protein 7 functions to restrict Notch1-positive progenitor cells to the tips of the prostate buds. Here, we employed prostate-specific murine bi-genic systems to investigate the effects of gain and loss of Notch function during prostate development. We show that Nkx3.1(Cre) and Probasin(Cre) alleles drive expression of Cre recombinase to the prostate epithelium and periepithelial stroma. We investigated the effects of gain of Notch function using the Rosa(NI1C) conditional allele, which carries a constitutively active intracellular domain of Notch1 receptor. We carried out the analysis of loss of Notch function in Nkx3.1(Cre/+);RBP-J(flox/flox) prostates, where RBP-J is a ubiquitous transcriptional mediator of Notch signaling. We found that gain of Notch function resulted in inhibition of the tumor suppressor PTEN, and increase in cell proliferation and progenitor cells in the basal epithelium and smooth muscle compartments. In turn, loss of Notch/RBP-J function resulted in decreased cell proliferation and loss of epithelial and smooth muscle progenitors. Gain of Notch function resulted in an early onset of benign prostate hyperplasia by three months of age. Loss of Notch function also resulted in abnormal differentiation of the prostate epithelium and stroma. In particular, loss of Notch signaling and increase in PTEN promoted a switch from myoblast to fibroblast lineage, and a loss of smooth muscle. In summary, we show that Notch signaling is necessary for terminal differentiation of the prostate epithelium and smooth muscle, and that during normal prostate development Notch/PTEN pathway functions to maintain patterned progenitors in the epithelial and smooth muscle compartments. In addition, we found that both positive and negative modulation of Notch signaling results in abnormal organization of the prostate tissue, and can contribute to prostate disease in the adult organ

OBJECTIVES: To evaluate the accuracy and potential clinical value of intraoperative frozen section analysis (FSA) on urethral margin (UM) tissue during radical prostatectomy. Positive surgical margins increase the risk of post-operative cancer recurrence. Positive surgical margins are frequently found at the apex. The utility of intraoperative FSA of the margins is controversial. METHODS: We reviewed a consecutive series of radical prostatectomy cases (n = 1669) performed at our institution, in which UMs were routinely evaluated by intraoperative FSA. RESULTS: The submitted UM tissue contained cancer glands in 111 cases (6.7%). On FSA, the pathologists detected cancer in 55 cases (3.3%), missed cancer in 38 (2.3%), and reported atypical glands in 18 (1.1%). FSA of the UMs had a sensitivity of 59.1%, specificity of 99.8%, and positive and negative predictive value of 94.8% and 97.6%, respectively. The low sensitivity resulted from a substantial false-negative rate (n = 38), which was largely attributed to limited sampling on FSA (n = 31). Of the 55 patients (3.3%) whose positive UMs were detected by FSA, 20 (1.2%) had cancer-free margins after tissue re-excision. A positive final UM was associated with greater biochemical recurrence (P = .0073). However, the few patients limited the statistical analysis of the benefit of margin conversion through tissue re-excision (P = .35). CONCLUSIONS: Although experienced pathologists can evaluate the UMs on FSA with good accuracy, FSA has a relatively low sensitivity. Our data have indicated a low yield and a questionable value of routine FSA during radical prostatectomy