Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests. RESULTS: Decipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82). CONCLUSIONS: Although Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

Oral administration of Lactobacillus strains from Kimchi inhibits atopic dermatitis in NC / Nga mice.

AIMS: Atopic dermatitis (AD) is marked by elevated levels of immunoglobulin E and skin lesions such as oedema and haemorrhage. Kimchi is a Korean fermented food that contains beneficial bacteria for human health. In this study, Lactobacillus plantarum CJLP55, CJLP56, CJLP133 and CJLP136 isolated from Kimchi were investigated for their capacity to inhibit AD. METHODS AND RESULTS: The three strains, CJLP55, CJLP133 and CJLP136, suppressed AD-like skin lesions, high serum IgE levels and epidermal thickening. The three strains diminished the accumulation of eosinophils and mast cells into topical inflammatory sites and the enlargement of axillary lymph nodes, which are responsible for the dorsal dermatitis. CJLP55, CJLP133 and CJLP136 decreased production of type 2 cytokines such as IL-4 and IL-5 in lymph node cell culture. CJLP133 and CJLP136 increased IFN-γ secretion, while CJLP55 enhanced IL-10 production. CONCLUSIONS: The three strains isolated from Kimchi suppress house-dust mite-induced dermatitis in NC/Nga mouse, a representative animal model of human AD. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that lactobacilli isolated from Kimchi inhibit AD, probably by altering the balance of Th1/Th2 ratio or inducing IL-10 production.

Tool Contact Acceleration Feedback for Telerobotic Surgery.

Minimally invasive telerobotic surgical systems enable surgeons to perform complicated procedures without large incisions. Unfortunately, these systems typically do not provide the surgeon with sensory feedback aside from stereoscopic vision. We have, thus, developed VerroTouch, a sensing and actuating device that can be added to Intuitive Surgical's existing da Vinci S Surgical System to provide auditory and vibrotactile feedback of tool contact accelerations. These cues let the surgeon feel and hear contact with rough textures as well as the making and breaking of contact with objects and other tools. To evaluate the merits of this approach, we had 11 surgeons use an augmented da Vinci S to perform three in vitro manipulation tasks under four different feedback conditions: with no acceleration feedback, with audio feedback, with haptic feedback, and with both audio and haptic. Subjects expressed a significant preference for the inclusion of tool contact acceleration feedback, although they disagreed over which sensory modality was best. Other survey responses and qualitative written comments indicate that the feedback may have improved the subject's concentration and situational awareness by strengthening the connection between the surgeon and the surgical instruments. Analysis of quantitative task metrics shows that the feedback neither improves nor impedes the performance of the chosen tasks.

The current state of robot assisted radical prostatectomy.

AIM: The introduction of robotics in the operating room made its first major impact in the arena of prostate cancer. Robot assisted radical prostatectomy (RARP) is the most commonly performed surgery for prostate cancer in the United States. METHODS: In this review article, we discuss the history of robotic prostatectomy as well as the benefits and drawbacks of the robotic surgical platform. Our University of Pennsylvania technique is described. Patient selection, peri-operative factors, oncological data, and functional outcomes specific to RARP are addressed. RESULTS: While cost remains a valid criticism to the robotic technique, some of the additional expenditure is offset by improved convalescence, fewer medical complications, and decreased morbidity. Data with follow up approaching 10 years demonstrates equal if not superior outcomes with respect to continence, sexual and oncological factors. CONCLUSION: The diligent efforts of many have led to the rapid evolution of robot assisted radical prostatectomy. There is a renewed interest in the anatomy, oncological outcomes, and functional consequences of prostatectomy. With technological advances occurring at an accelerating rate, the advances in surgery should be very exciting indeed.

Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells.

BACKGROUND: The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). OBJECTIVES: To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). METHODS: Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebo-treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-beta mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. RESULTS: Foxp3(+) cells were increased in the oral epithelium of SLIT- vs. placebo-treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT- compared with placebo-treated atopics (P=0.1 for both). IgG(1) and IgG(4) were increased following SLIT (P<0.001). Peak seasonal IgA(1) and IgA(2) were increased during SLIT (P<0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics. CONCLUSIONS: SLIT with grass pollen extract is associated with increased Foxp3(+) cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

The role of vacuum erection devices in penile rehabilitation after radical prostatectomy.

Even nerve-sparing radical prostatectomy damages the cavernous nerves and leads to temporary erectile dysfunction (ED) in men recovering from prostate cancer surgery. Historically, patients recovering from prostate cancer surgery have been advised that the return of erectile function (EF) can take from 6 to 18 months, or even longer. Unfortunately, the return of sexual function in these patients remains variable, but is generally thought to be dependent on the individual patient's pre-surgery EF, as well as the degree of cavernous nerve disruption during prostate removal. Recently, there has been a growing movement to proactively treat patients postoperatively for presumed nerve damage to stimulate nerve recovery and possibly reduce the degree of irreversible damage. This would reduce the on-demand therapy these patients would require, and hopefully remove the requirement for an implantable prosthesis. The underlying hypothesis is that the artificial induction of erections shortly after surgery facilitates tissue oxygenation, reducing cavernosal fibrosis in the absence of nocturnal erections, potentially increasing the likelihood of preserving EF. Vacuum erection devices (VED), because of their ability to draw blood into the penis regardless of nerve disturbance, have become the centerpiece of penile rehabilitation protocols. This review will discuss the pathophysiology of radical prostatectomy induced ED and the rationale for rehabilitation. It will then discuss current protocols, including those involving the VED.

Phenylephrine hypertrophy, Ca2+-ATPase (SERCA2), and Ca2+ signaling in neonatal rat cardiac myocytes.

We endeavored to use a basic and well-controlled experimental system to characterize the extent and time sequence of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) involvement in the development of cardiac hypertrophy, including transcription, protein expression, Ca(2+) transport, and cytoplasmic Ca(2+) signaling. To this end, hypertrophy of neonatal rat cardiac myocytes in culture was obtained after adrenergic activation with phenylephrine (PE). Micrographic assessment of myocyte size, rise of [(14)C]phenylalanine incorporation and total protein expression, and increased transcription of atrial natriuretic factor demonstrated unambiguously the occurrence of hypertrophy. An early and prominent feature of hypertrophy was a reduction of the SERCA2 transcript, as determined by RT-PCR with reference to a stable marker such as glyceraldehyde-3-phosphate dehydrogenase. Reduction of Ca(2+)-ATPase protein levels and Ca(2+) transport activity to approximately 50% of control values followed with some delay, evidently as a consequence of a primary effect on transcription. Cytosolic Ca(2+) signaling kinetics, measured with a Ca(2+)-sensitive dye after electrical stimuli, were significantly altered in hypertrophic myocytes. However, the effect of PE hypertrophy on cytosolic Ca(2+) signaling kinetics was less prominent than observed in myocytes subjected to drastic SERCA2 downregulation with small interfering RNA or inhibition with thapsigargin (10 nM). We conclude that SERCA2 undergoes significant downregulation after hypertrophic stimuli, possibly due to lack of SERCA gene involvement by the hypertrophy transcriptional program. The consequence of SERCA2 downregulation on Ca(2+) signaling is partially compensated by alternate Ca(2+) transport mechanisms. These alterations may contribute to a gradual onset of functional failure in long-term hypertrophy.

Hematopoietic effect of ginsenoside Rg3 in ICR mouse primary cultures and its application to a biological response modifier.

Ginsenoside Rg3, which is obtained as a by-product during the steaming of red ginseng, at 300 microg/ml enhanced the proliferation of the total spleen and bone marrow (BM) cells in both the cyclophosphamide (CYC)-treated and non-CYC-treated groups.

Laparoscopic radical prostatectomy: review and assessment of an emerging technique.

BACKGROUND: Several recent reports have affirmed the feasibility of the laparoscopic approach for radical prostatectomy. In this review, we discuss the morbidities associated with this technique and compare outcomes and convalescence with standard open radical prostatectomy. METHODS: We reviewed all currently published data on laparoscopic radical prostatectomy and our series of 45 robotic-assisted radical prostatectomies and compared them to several landmark series of open retropubic and perineal radical prostatectomies. RESULTS: Although the initial series reported long operating times, these times have been significantly reduced in more recent series. Data on blood loss, convalescence, impotence, and incontinence rates have also been promising. CONCLUSIONS: Although follow-up has been short thus far, laparoscopic radical prostatectomy has been shown to be similar to open radical prostatectomy in several areas.

Nitrification of high strength ammonia wastewater and nitrite accumulation characteristics.

Biological nitrogen removal via the nitrite pathway in wastewater treatment is very important in saving the cost of aeration and as an electron donor for denitrification. Wastewater nitrification and nitrite accumulation were carried out in a biofilm airlift reactor with autotrophic nitrifying biofilm. The biofilm reactor showed almost complete nitrification and most of the oxidized ammonium was present as nitrite at the ammonium load of 1.5 to 3.5 kg N/m3 x d. Nitrite accumulation was stably achieved by the selective inhibition of nitrite oxidizers with free ammonia and dissolved oxygen limitation. Stable 100% conversion to nitrite could also be achieved even under the absence of free ammonia inhibition on nitrite oxidizers. Batch ammonium oxidation and nitrite oxidation with nitrite accumulating nitrifying biofilm showed that nitrite oxidation was completely inhibited when free ammonia is higher than 0.2 mg N/L. However, nitrite oxidation activity was recovered as soon as the free ammonia concentration was below the threshold level when dissolved oxygen concentration was not the limiting factor. Fluorescence in situ hybridization analysis of cryosectioned nitrite accumulating nitrifying biofilm showed that the beta-subclass of Proteobacteria, where ammonia oxidizers belong, was distributed outside the biofilm whereas the alpha-subclass of Proteobacteria, where nitrite oxidizers belong, was found mainly in the inner part of the biofilm. It is likely that dissolved oxygen deficiency or limitation in the inner part of the nitrifying biofilm, where nitrite oxidizers exist, is responsible for the complete shut down of the nitrite oxidizers activity under the absence of free ammonia inhibition.

Long-term effects of ureteroscopic laser lithotripsy on glomerular filtration rate in the face of mild to moderate renal insufficiency.

BACKGROUND AND PURPOSE: Ureteroscopic laser treatment of calculi in the upper urinary tract was examined in regard to its effect on renal function in the setting of mild renal insufficiency. Percutaneous nephrolithotomy (PCNL) and SWL have been previously shown not to adversely affect the glomerular filtration rate (GFR) in renal insufficiency, but to our knowledge, the effect of ureteroscopic laser lithotripsy on GFR has not been previously reported. PATIENTS AND METHODS: A retrospective review of all cases of ureteroscopic laser lithotripsy at our institution was performed. A total of 18 patients with a baseline serum creatinine of > or = 1.5 mg/dL were found. The mean follow-up after treatment was 18.0 months (range 4-39 months). The change in the reciprocal of serum creatinine was used as an indicator of change in the GFR. Deterioration of 20% was considered significant. RESULTS: The overall mean change in treated patients was a 5.9% improvement. Patients with a preoperative creatinine of < 2.0 mg/dL improved 7.6% and those with creatinine of > or = 2.0 mg/dL increased 3.9%. Other factors such as the size of the stone, location of the stone, and total joules used during treatment were not significant. CONCLUSION: This examination suggests that ureteroscopic laser lithotripsy has no ill effects on renal function in the face of mild to moderate renal insufficiency.

Intraoperative mild hypothermia does not increase the plasma concentration of stress hormones during neurosurgery.

PURPOSE: To determine how mild hypothermia (34 degrees C) affects the hemodynamic and the stress hormonal responses intraoperatively and during extubation in patients undergoing cerebral aneurysm surgery. METHODS: After induction, anesthesia was maintained with 1.2% isoflurane and 50% nitrous oxide. For the normothermia and the hypothermia groups, the body temperature was maintained at 36.9 +/- 0.3 degrees C and 34.2 +/- 0.2 degrees C respectively up to the recovery room. Hemodynamic changes were recorded continuously. Stress hormones comprising epinephrine, norepinephrine, ADH, ACTH, and cortisol were measured at the awake control, intraoperative, and extubation periods. RESULTS: Vital signs of the intraoperative and postextubation time periods were not significantly different between the normothermia and hypothermia groups except for a statistically lower pulse rate intraoperatively in the hypothermia group (P <0.05). In the control awake state, all five hormonal concentrations were similar between the two groups. Intraoperatively, all of the hormonal levels tended to be lower in the hypothermia group compared to the normothermia group, but only the epinephrine level decreased sufficiently to reach statistical significance (P <0.05). During extubation, all stress hormone concentrations, except norepinephrine, were lower in the hypothermia group (epinephrine: P <0.05; ADH: P <0.05; ACTH: P <0.05; cortisol: P <0.05). CONCLUSIONS: Our data suggest that intraoperative mild hypothermia neither significantly affects the blood pressure response nor increases the concentrations of stress hormones intraoperatively. Furthermore, mild hypothermia significantly decreased the plasma concentrations of stress hormones during the extubation period.

Flail aortic valve and acute aortic regurgitation due to spontaneous localized intimal tear of ascending aorta.

This report describes the transesophageal echocardiographic findings of acute severe aortic regurgitation resulting from localized transverse intimal tear of ascending thoracic aorta which could not be suspected as a cause of flail aortic valve preoperatively. In patients with chest pain and acute aortic regurgitation associated with flail aortic valve, localized intimal tear of aorta should be considered as a possible cause of flail aortic valve.

Experience with endoluminal ultrasonography in the urinary tract.

Ultrasonography has been an invaluable tool in the field of urology for its noninvasiveness, safety, and relatively low cost. However, examination of the ureter with ultrasound is difficult because of the distance of the transducer from the ureter and because of intervening structures such as nonconductive bowel gas. As smaller probes have become available, attempts have been made to apply them to endoluminal use. Endoluminal ultrasonography has been employed in urology to examine the proper placement of injected collagen, diagnose urethral diverticula, diagnose and stage upper tract transitional-cell carcinoma, locate crossing vessels to guide endopyelotomy, diagnose submucosal calculi, and examine the severity and length of ureteral strictures.

Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa.

Recently, we cloned and characterized a full-length cDNA of the hamster Muc1 gene, the expression of which appears to be associated with secretory cell differentiation (Park HR, Hyun SW, and Kim KC. Am J Respir Cell Mol Biol 15: 237-244, 1996). The role of Muc1 mucins in the airway, however, is unknown. In this study, we investigated whether cell surface mucins are adhesion sites for Pseudomonas aeruginosa. Chinese hamster ovary (CHO) cells not normally expressing Muc1 mucin were stably transfected with the hamster Muc1 cDNA, and binding to P. aeruginosa was examined. Our results showed that 1) stably transfected CHO cells expressed both Muc1 mRNA and Muc1 mucins based on Northern and Western blot analyses, 2) Muc1 mucins present on the cell surface were degraded by neutrophil elastase, and 3) expression of Muc1 mucins on the cell surface resulted in a significant increase in adhesion of P. aeruginosa that was completely abolished by either proteolytic cleavage with neutrophil elastase or deletion of the extracellular domain by mutation. We conclude that Muc1 mucins expressed on the surface of CHO cells serve as adhesion sites for P. aeruginosa, suggesting a possible role for these glycoproteins in the early stage of airway infection and providing a model system for studying epithelial cell responses to bacterial adhesion that leads to airway inflammation in general and cystic fibrosis in particular.

The effects of morphine on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

UNLABELLED: This study was performed to evaluate whether morphine could alter the degree of disruption of the blood-brain barrier (BBB) caused by hyperosmolar mannitol. Under isoflurane anesthesia, rats in a control group were infused with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (Ki) of (14)C-alpha-aminoisobutyric acid. Infusion of morphine 3 mg/kg in the small-dose morphine group and 10 mg/kg in the large-dose morphine group was completed, 10 min before administering mannitol. There were no statistical differences in systemic blood pressures between these three groups of animals. In the control group, the Ki of the ipsilateral cortex where mannitol was injected, increased to 4.6 times that of the contralateral cortex (19.5 +/- 8.5 vs 4.2 +/- 1.2 microL. g(-1). min(-1), P < 0.002). The Ki of the ipsilateral cortex of the small-dose morphine group was 13.5 +/- 7.6 microL. g(-1). min(-1). The Ki of the ipsilateral cortex of the large-dose morphine group was 9.2 +/- 4.5 microL. g(-1). min(-1) and was smaller than that of control animals (P < 0.05). There was no significant difference in the Ki of the contralateral cortex among the three groups. In conclusion, morphine attenuated BBB disruption induced by hyperosmolar solution without significant effects on systemic blood pressure. IMPLICATIONS: Our study suggests that morphine may be effective in reducing the blood-brain barrier disruption by hyperosmolar mannitol without significant effects on systemic blood pressure.

Transesophageal echocardiographic identification of left upper pulmonary venous obstruction caused by compression by spontaneous pseudoaneurysm of the descending thoracic aorta.

Pseudoaneurysm of the aorta usually occurs as a complication of nonpenetrating trauma or deceleration injuries. Spontaneous pseudoaneurysm of the aorta is, however, extremely rare. Pulmonary veins can be affected in this situation because of the anatomic proximity. However, it is often overlooked during clinical examination, during routine echocardiography, and even at invasive angiography. This report describes the importance of transesophageal echocardiography in the detection of pulmonary vein compression, which is not suspected during other noninvasive and invasive diagnostic tests, in a patient with spontaneous pseudoaneurysm of the descending thoracic aorta.

Identification and characterization of high molecular-mass mucin-like glycoproteins in the plasma membrane of airway epithelial cells.

A previous lectin binding study demonstrated the presence of high molecular-mass mucin-like glycoproteins (HMGP) on the surface of hamster tracheal surface epithelial (HTSE) secretory cells (Proc. Natl. Acad. Sci. USA 1987;84:9304). In the present study, we intended to isolate and characterize these HMGP from the plasma membrane of the primary HTSE cells and then to determine whether or not these membrane HMGP are Muc-1 mucins, a type of mucins originally discovered on the surface of some carcinomas. A subcellular fraction enriched with the plasma membrane was obtained using a sucrose density gradient centrifugation. This fraction contained high molecular-mass glycoconjugates which were excluded from Sepharose CL-4B gel. Biochemical characterization of these glycoconjugates revealed the following characteristics: (1) susceptibility to both pronase and mild alkaline treatments, but totally resistant to proteoglycan-digesting enzymes; (2) partitioning in the detergent phase of Triton X-114 and resistance to digestion by phosphatidylinositol phospholipase C or D; (3) a buoyant density of 1.5 g/ml based on CsCl density gradient centrifugation; (4) polydispersity in terms of both size and charge density; and (5) lack of immunoreactivity with an anti-Muc-1 mucin antibody. We conclude that the plasma membrane of HTSE cells at confluence contains HMGP, which seem to be the integral membrane proteins but different from Muc-1 mucins, and that these membrane HMGP appear to share some similarities with secreted mucins in terms of size and charge.

Cloning and characterization of cDNAs coding for heavy and light chains of a monoclonal antibody (MabA34) specific for human plasma apolipoprotein A-I.

We have determined the nucleotide (nt) sequences encoding the heavy (H)- and light (L)-chains of the Fab fragment of a murine monoclonal antibody, MabA34 (gamma1, kappa), which is specific for human plasma apolipoprotein A-I of high-density lipoproteins. The variable (V) regions of the H- and L-chains were revealed to be members of mouse H-chain subgroup II(A) and kappa L-chain subgroup II, respectively. A few unusual amino acids in the V region of the H-chain, and nt residues probably introduced by somatic mutations from germline genes were also identified.