Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer

Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression.     

Utility of MR urography in children suspected of having ectopic ureter

Background

Conventional imaging modalities are limited in the assessment of complex lower urinary tract anomalies including ectopic insertion of ureters. MR urography can be useful in these situations.

Objective

To share our experience with MR urography in assessing lower urinary tract anomalies and to determine its accuracy in depicting ectopic ureters.

Materials and methods

We conducted a retrospective review of all MR urography examinations done between November 2007 and March 2013 to note the presence or absence of duplex kidneys and insertion of ureters. We reviewed patient charts, surgical findings and results of other investigations including cystoscopy with retrograde ureterogram in order to establish presence or absence of ectopic ureter. This served as a reference standard against which we compared MR urography results.

Results

Of 22 MR urography examinations (3 boys, 19 girls; age range 3–16 years, mean 9.2 years) performed during the study period, 19 were performed to rule out ectopic ureters, two to assess complex anatomy and one to rule out crossing vessel in ureteropelvic junction obstruction. MR urography showed ectopic ureter in 9/19 children; one proved to be a false-positive. MR urography correctly showed normal insertion in 7/19 children. In the remaining 3/19 children distal ureter could not be seen, hence insertion was indeterminate on MR urography. One of these children had an ectopic ureter on cystoscopy and surgery. Statistical analysis showed MR urography’s sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to be 88.8–100%, 70–90%, 75–88.8% and 90–100% for the detection of ectopic ureter.

Conclusion

MR urography is highly accurate in the assessment of ectopic ureters. In incontinent girls, MR urography should be the method of choice for depicting or ruling out ectopic ureter.     

Evolution of Visceral Sensitivity in Patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) has been associated with visceral hypersensitivity. Here we examined the evolution of rectal sensitivity and of gastrointestinal symptomatology in IBS patients over time, to verify if the clinical and biological parameters showed parallel behavior. Patients complaining of IBS, identified by Rome 1 criteria, were included in this study. The severity of the gastrointestinal (Gastrointestinal) symptoms was assessed by a gastrointestinal index. The pain threshold to rectal distension was measured by a barostat programmed for phasic ascending distensions. Both measures were obtained before and after treatment. Thirty-nine patients were followed while on a 10-week group psychotherapy (psy) program. Twelve patients were controlled after pharmacological treatment with amitriptyline (Ami) 10 mg hours for two weeks and then 25 mg hours for the following 4 weeks. Clinical improvement with symptom reduction was achieved in both patients groups. With psy, the Gastrointestinal index declined from an initial value of 78.4 ± 4.8 to 65.5 ± 4.5 at the end of treatment (P < 0.05). With Ami, the gastrointestinal index decreased from 91.6 ± 5.6 to 61.8 ± 9.1 (p < 0.01). The pain threshold to rectal distension increased from 27.7 ± 1.0 to 33.7 ± 1.9 mmHg (P < 0.01) after drug treatment, but remained unchanged (30.6 ± 1.0 vs 30.6 ± 1.1 mm Hg) with psy. Evolution of the gastrointestinal index and rectal sensitivity were directly correlated (r = –0.71; P < 0.01) in Ami patients, but not in those treated with Psy (r = –0.001). In conclusion, visceral hypersensitivity appeared as a stable biological defect over a 10- to 12-week period during clinically-effective treatment with psychotherapy. Rectal pain threshold, however, seemed to be pharmacologically manipulatable in patients treated with Ami.     

Serial MRI characterization of the functional and morphological changes in mouse lung in response to cardiac remodeling following myocardial infarction

The temporal evolution of heart failure and associated pulmonary congestion in rodent heart failure models has not yet been characterized simultaneously and noninvasively. In this study, MRI was used to assess the serial progression of left‐ventricular dysfunction and lung congestion in mice following myocardial infarction (MI). Cardiac and lung ¹H MRI was performed at baseline and every 3 days up to 13 days postsurgery in sham and MI mice. Respiratory parameters and terminal lung mechanics were assessed followed by histological analysis. MRI revealed that the MI induced significant pulmonary congestion/edema as detected by increased MRI signal intensity and was associated with increased lung volume and reduced cardiac contractility. Pulmonary function was also depressed in MI‐mice, reflected by a reduced tidal volume and a low minute ventilation rate. Additionally, MI significantly increased lung resistance, markedly reduced lung compliance and total lung capacity and significantly increased lung weights by 57%. Significant correlations were observed between the MRI measured lung congestion, lung volume, ejection fraction, and lung wet‐weight parameters. This study demonstrates that MRI may be of significant value in evaluating therapies aimed at primary intervention for lung congestion and secondary prevention of unfavorable cardiac remodeling. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Characterization of lymphocyte responses to peanuts in normal children,peanut-allergic children,and allergic children who acquired tolerance to peanuts

Comparing lymphocyte responses to allergenic and nonallergenic foods could reveal the differences between pathogenic and normal immune responses to foods. Defining the cytokine-producing phenotypes of peanut-specific lymphocytes from peanut-allergic children, children who outgrew peanut allergy, and children who have always tolerated peanuts may be useful for understanding the mechanisms of food tolerance. Investigating immune responses against foods is hindered, however, by the fact that circulating food antigen-specific lymphocytes are very rare. In a novel approach we used carboxyfluorescein succinimidyl ester to detect peanut-specific lymphocytes by flow cytometry. We confirmed that these cells are indeed peanut specific by cloning. Peanut-allergic donors show Th2 polarization of cytokine production by peanut-specific cells (IFN-gamma (low), TNF-alpha (low), IL-4 (high), IL-5 (high), IL-13 (high)). Conversely, nonallergic children and children who have outgrown their allergy show Th1 skewing to peanut antigens (IFN-gamma(high), TNF-alpha (high), IL-4 (low), IL-5 (low), IL-13(low)), similarly to nonallergenic food antigens (beta-lactoglobulin, OVA). This finding suggests that peanut antigens do not intrinsically induce Th2 skewing, but that the type of response depends upon the donor's allergic status. In conclusion, food allergic status is characterized by a Th2 response whereas Th1-skewed responses underlie oral tolerance.     

Music Does Not Reduce Alfentanil Requirement During Patient-Controlled Analgesia (PCA) Use in Extracorporeal Shock Wave Lithotripsy for Renal Stones

To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia (PCA), we conducted a prospective, blinded, randomized controlled trial. Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music. They were then premedicated with morphine and ketorolac and randomly allocated into two groups. Group 1 (n = 97) had music started 10 min before the procedure and maintained until 10 min after its conclusion. Group 2 (n = 96) had music begun at the conclusion of lithotripsy and continued for 10 min. Pain intensity, alfentanil requirement, side effects, quality of analgesia, patient satisfaction, and acceptance of the technique were evaluated. Demographics, alfentanil requirement, pain levels, side effects, quality of analgesia, and patient satisfaction were similar in both groups. The addition of music did not provide any benefit. This result raises the possibility that some nonpharmacologic therapies have minimal impact in settings where the painful stimulus is moderate to severe and adequate pharmacotherapy is available.