Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which ...metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.
We present the Team Keck Redshift Survey 2 (TKRS2), a near-infrared spectral observing program targeting selected galaxies within the CANDELS subsection of the GOODS-North Field. The TKRS2 program ...exploits the unique capabilities of the Multi-Object Spectrometer For Infra-Red Exploration (MOSFIRE), which entered service on the Keck I telescope in 2012 and contributes substantially to the study of galaxy spectral features at redshifts inaccessible to optical spectrographs. The TKRS2 project targets 97 galaxies drawn from samples that include z asymptotically = 2 emission-line galaxies with features observable in the JHK bands as well as lower-redshift targets with features in the Y band. We present a detailed measurement of MOSFIRE's sensitivity as a function of wavelength, including the effects of telluric features across the YJHK filters. The largest utility of our survey is in providing rest-frame-optical emission lines for z > 1 galaxies, and we demonstrate that the ratios of strong, optical emission lines of z asymptotically = 2 galaxies suggest the presence of either higher N/O abundances than are found in z asymptotically = 0 galaxies or low-metallicity gas ionized by an active galactic nucleus. We have released all TKRS2 data products into the public domain to allow researchers access to representative raw and reduced MOSFIRE spectra.
To assess long term functional and safety follow-up data after 80-W GreenLight photoselective vaporization (GL PV) of the prostate and transurethral resection of the prostate (TURP).
Prospective ...randomized trial at a single tertiary referral center (Geneva, Switzerland). Patients were recruited in the outpatient clinic if they met the criteria for surgical treatment of benign prostatic obstruction. At baseline, 238 patients were treated either with the 80-W GL PV or monopolar TURP. After 5 years, data were available from 105 patients: 44 GL PV patients and 61 TURP patients. The primary outcome measure was the International Prostate Symptom Score (IPSS). Secondary outcome measures included maximum urinary flow rate (Qmax), postvoidal residual (PVR) and reoperation rate. Statistical analyses were performed using Stata 14 (StataCorp).
After 5 years of follow-up, mean improvements in International Prostate Symptom Score, postvoidal residual and maximum urinary flow rate were similar in both groups. The re-treatment rate was 14.3% in the GL PV group vs 11.9% in the TURP group (P = .9).
Noninferiority of the GL PV to TURP was confirmed in all functional and safety outcomes at 5-year follow-up. GL-PV could be a safe surgical alternative for patients suffering from benign prostatic obstruction.
Perineural invasion (PNI) after radical prostatectomy (RP) is a common feature of prostate cancer (PCa) and has been associated with unfavorable tumor characteristics. However, its prognostic ...relevance is controversial. In this study, we evaluated the impact of both PNI status (PNI+ versus PNI−) and quantified number of PNI focus on the long-term prognosis of biochemical recurrence (BCR) after RP. After reevaluating PNI of a total of 721 patients with localized PCa who underwent RP at our institution between 2000 and 2002, we examined associations between PNI status or PNI focus number and clinicopathological factors including tumor stage, Gleason score, margin status, tumor location, preoperative prostate specific antigen, age, prostate weight as well as BCR outcome. PNI was present in 530 of 721 cases (73.5%) of the RP specimens and was associated with more aggressive disease. BCR occurred in 19.4% of all patients within a median follow-up period of 8.5 years. PNI+ status was associated with poor BCR prognosis in univariate analysis but lost in multivariate analysis. Based on the number of PNI focus, PNI was further divided into 2 distinct group: PNI+ a (≤3) and PNI+ b (>3). In a multivariate Cox regression model, PNI+ b (>3) was identified as an independent BCR prognostic factor. Quantification of PNI focus number beside the dichotomized status recording will not only provide more detailed information but also be a novel prognostic indicator for risk stratification. Further external validation will be needed for an optimal cut-off value of the PNI focus number. Our findings will help further research on the relevance of PNI in the pretreatment setting and support ongoing efforts to understand its role of cancer progression.
To report our experience with robot-assisted ureteral anastomosis for kidney graft. Kidney graft complex ureteral strictures or symptomatic vesicoureteral reflux may require complex reconstruction. ...This is classically done through an open surgical access, which adds to the morbidity of kidney transplantation. The da Vinci robot enables performance of complex laparoscopic procedures and may hence be used for such reconstructions.
We retrospectively reviewed all patients undergoing robotic surgical revision for stricture or reflux disease over a 3-year period. Contemporary patients who underwent open surgery were used as a control group.
Ten patients underwent a robotic attempt, of whom 4 needed conversion to open surgery. Seven patients underwent an open surgery. Preoperative demographics were similar in both groups. The median operative time was 293 minutes, with a shorter operative time in the open group. The group of patients who could be completed robotically had a significantly lower postoperative length of stay (5 vs 9 days), quicker return to normal food intake (postoperative day 1 vs 3), and quicker control of pain without opiates (postoperative day 1 vs 4) than the converted or open group. Morbidity was comparable with 1 late Clavien IIIb complication in each subgroup (open, converted, and robotic group). After a median follow-up of 43 months, renal function was stable and there were no recurrent graft infections.
Robotic ureteral reconstruction for kidney graft patients is feasible and efficient, and offers the classical advantages of minimally invasive surgery with outcomes comparable with open series.
Study Type – Therapy (case series) Level of Evidence 4
OBJECTIVE
To assess how advances in urology, radiology and orthopaedics are changing the current management of bladder ruptures, by reviewing ...patients treated for bladder ruptures after blunt trauma.
PATIENTS AND METHODS
Our database was screened for patients admitted with bladder ruptures between 1980 and 2008. Charts were reviewed for demographics, clinical variables, diagnostics, treatment and outcome.
RESULTS
Thirty‐six patients with extraperitoneal (EPR, 61%) and intraperitoneal (IPR) or combined ruptures (39%) were identified; 81% of them presented pelvic‐ring fractures. Diagnosis relied on computed tomography cystography (CT‐C), which has replaced plain‐film cystography. The sensitivity of either type of cystography was >90%. However, three bladder ruptures (11%) were missed on CT‐C performed with insufficient bladder distension. All 14 patients with IPRs had immediate surgical repair, four of them by laparoscopy. Twelve of 22 EPRs (55%) were sutured during concomitant orthopaedic/visceral surgery or because of the urologist’s apprehension of infection. Only eight of 22 patients with EPR (36%) completed conservative treatment.
CONCLUSIONS
Diagnosis relies increasingly on CT‐C, allowing simultaneous assessment of multiple organ systems. However, only specific CT‐C guarantees an adequate sensitivity. Orthopaedists increasingly use open reductions and fixation of pelvic‐ring fractures, prompting urologists to suture EPRs simultaneously. Our data indicate that this proactive management reduces infectious complications, and we have adopted it as the standard of care in our institution. Laparoscopic suture is an advantageous treatment of isolated IPR.
We analyze the spatial and velocity distributions of confirmed members in five massive clusters of galaxies at intermediate redshift (0.5 < z < 0.9) to investigate the physical processes driving ...galaxy evolution. Based on spectral classifications derived from broad- and narrow-band photometry, we define four distinct galaxy populations representing different evolutionary stages: red sequence (RS) galaxies, blue cloud (BC) galaxies, green valley (GV) galaxies, and luminous compact blue galaxies (LCBGs). For each galaxy class, we derive the projected spatial and velocity distribution and characterize the degree of subclustering. We find that RS, BC, and GV galaxies in these clusters have similar velocity distributions, but that BC and GV galaxies tend to avoid the core of the two z approximately 0.55 clusters. GV galaxies exhibit subclustering properties similar to RS galaxies, but their radial velocity distribution is significantly platykurtic compared to the RS galaxies. The absence of GV galaxies in the cluster cores may explain their somewhat prolonged star-formation history. The LCBGs appear to have recently fallen into the cluster based on their larger velocity dispersion, absence from the cores of the clusters, and different radial velocity distribution than the RS galaxies. Both LCBG and BC galaxies show a high degree of subclustering on the smallest scales, leading us to conclude that star formation is likely triggered by galaxy-galaxy interactions during infall into the cluster.
Micro-Abstract Neoadjuvant chemotherapy (NAC) has been demonstrated to be effective in prospective randomized trials for cT2-cT4a N0 patients. However, this benefit was more evident in patients with ...clinical stage ≥ T3 disease. On the other hand, toxicity grade 3 and 4 were reported in 35% and 37% of patients who underwent NAC. Following these considerations, we validate here the preoperative risk model proposed by Culp et al as a fundamental tool in the preoperative prediction of patients who will benefit more from NAC administration.
ABSTRACT Luminous Compact Blue Galaxies (LCBGs) are an extreme star-bursting population of galaxies that were far more common at earlier epochs than today. Based on spectroscopic and photometric ...measurements of LCBGs in massive (M > 1015 M ), intermediate redshift (0.5 < z < 0.9) galaxy clusters, we present their rest-frame properties including star formation rate, dynamical mass, size, luminosity, and metallicity. The appearance of these small, compact galaxies in clusters at intermediate redshift helps explain the observed redshift evolution in the size-luminosity relationship among cluster galaxies. In addition, we find the rest-frame properties of LCBGs appearing in galaxy clusters are indistinguishable from field LCBGs at the same redshift. Up to 35% of the LCBGs show significant discrepancies between optical and infrared indicators of star formation, suggesting that star formation occurs in obscured regions. Nonetheless, the star formation for LCBGs shows a decrease toward the center of the galaxy clusters. Based on their position and velocity, we estimate that up to 10% of cluster LCBGs are likely to merge with another cluster galaxy. Finally, the observed properties and distributions of the LCBGs in these clusters lead us to conclude that we are witnessing the quenching of the progenitors of dwarf elliptical galaxies that dominate the number density of present-epoch galaxy clusters.
Abstract Purpose The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with ...oncological outcomes. Methods This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes. Results HER2 was overexpressed in 36% of patients. HER2 overexpression was associated with features of tumor aggressiveness such as lymph-node metastases ( P = 0.002). At a median follow-up of 123 months (interquartile range: 79–180), 160 patients (45%) experienced disease recurrence, 263 patients (74%) died and 157 (44%) died of cancer. On multivariable analyses, HER2 overexpression was not significantly associated with any oncological outcomes. Adding HER2 status to a model for the prediction of survival outcomes did not change the accuracy of the model for any of the outcomes. Interestingly, HER2 status significantly affected late disease recurrence ( P = 0.05 for conditional survival at 24 months). Conclusions More than one third of RC patients overexpress HER2 in their tumors. HER2 overexpression was associated with features of biological and clinical aggressiveness. HER2 did not add prognostic significance to the standard established predictors of survival outcomes after RC. However, due to the high overexpression rate, it could represent a target for therapy in select advanced BCa tumors.
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