Role of Serum High-Sensitivity C-Reactive Protein as a Predictor of Therapeutic Response to Tadalafil in Patients With Erectile Dysfunction: A Prospective Observational Study.

INTRODUCTION: High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is known to be elevated in patients with erectile dysfunction (ED). However, its role in predicting therapeutic response to phosphodiesterase-5 inhibitors is incompletely understood. AIM: The aim of this study was to understand the relationship among hs-CRP, mechanism of ED, and therapeutic response of ED to tadalafil, a phosphodiesterase-5 inhibitor. METHODS: A total of 282 men (mean age 36.6 ± 12.0 years) with ED were included. All subjects underwent detailed evaluation, including estimation of a 6-item abbreviated version of the International Index of Erectile Function (IIEF-6) score, penile Doppler studies, and measurement of hs-CRP. IIEF-6 scoring and hs-CRP measurement were repeated after 6 weeks of tadalafil therapy (10 mg/day). The patients were categorized into vasculogenic and nonvasculogenic ED groups based on penile Doppler findings. MAIN OUTCOME MEASURE: The main outcome measure was the therapeutic response to tadalafil, in relation to the mechanism of ED and hs-CRP levels. RESULTS: Vasculogenic ED was much less common (23.8% of the subjects) than non-vasculogenic ED. Subjects with vasculogenic ED were older, had higher prevalence of cardiovascular risk factors, had more severe (mean IIEF-6 score 9.2 ± 4.6 vs 14.8 ± 4.7; P < .001) and longer duration ED, and responded less favorably to therapy (response rate 10.4% vs 75.0%; P < .001). Those showing improvement with tadalafil had lower hs-CRP at baseline (median 1.5 mg/L [interquartile range 0.9-2.3] vs 2.0 mg/L [interquartile range 1.1-3.1; P = .034]) and had proportionately greater reduction in its level. However, on multivariate analysis, only shorter duration of ED (P = .008), non-vasculogenic origin (P = .025), and higher IIEF-6 score at baseline (P = .013) were independent predictors of response to treatment. CLINICAL IMPLICATIONS: Serum hs-CRP is elevated in patients who are less likely to respond to vasodilator therapy but does not have an independent predictive value for this purpose. STRENGTHS & LIMITATIONS: This is the largest study to evaluate the relationship among the mechanism of ED, serum hs-CRP level, and therapeutic response of ED to tadalafil. All patients underwent a penile Doppler study to characterize the type of ED. The limitations were nonrandomized nature of the study and nearly 22% dropout rate. CONCLUSION: Serum hs-CRP level is higher in vasculogenic ED compared with non-vasculogenic ED, and is associated with poorer response to tadalafil therapy. However, this association is not independent of underlying risk factors and mechanism of ED. Jamaluddin, Bansal M, Srivastava GK, et al. Role of Serum High-Sensitivity C-Reactive Protein as a Predictor of Therapeutic Response to Tadalafil in Patients With Erectile Dysfunction: A Prospective Observational Study. J Sex Med 2019;16:1912-1921.

Assessment of the performance of Partin's nomogram (2007) in contemporary Indian cohort.

INTRODUCTION: Partin's nomogram is an important prognostic tool to predict adverse pathological features for clinically localized prostate carcinoma. This tool is widely used by both radiation and surgical oncologists for pre-intervention counseling, treatment planning, and predicting the possible need for adjuvant treatment. However, the model is derived from a Western population with typical characteristics of prostate cancer in a prostate-specific antigen (PSA) screened population. Therefore, this study was conducted to assess the performance of the Partin's nomogram as applied to an Indian cohort by assessing the discrimination and calibration properties. METHODS: A retrospective review of 282 patients treated with robotic radical prostatectomy from 2010 to 2015 was conducted. Partin tables (year 2007) were used to calculate the predicted probabilities for lymph node invasion (LNI), seminal vesicle invasion (SVI), and extraprostatic extension (EPE). The discrimination properties were assessed using the receiver operating characteristic (ROC) curves. Calibration of the model was done to show the relationship between predicted and observed values. RESULTS: The mean age of the patients was 64.3 years. Most (59.4%) were clinical T2 disease. Patients with PSA >10 ng/ml comprised 60% of the population. ECE, SVI, and LNI were present in 39.2%, 22%, and 11% of cases, respectively. ROC analysis revealed area under curve values for EPE, SVI, and LNI of 68%, 67.5%, and 71.2%, respectively. Calibration plot suggested that the Partin tables under-predicted the risk whenever the values of predicted risk were more than 26%, 3%, and 1% for EPE, SVI, and LNI, respectively, and over predicted when the risk was lower. CONCLUSION: Our data show that Partin's tables, despite having fair discrimination properties, do not accurately predict LNI, SVI, and ECE across the entire range of predicted values in a contemporary Indian cohort.

Analysis of outcome following robotic assisted radical prostatectomy for patients with high risk prostate cancer as per D'Amico classification.

INTRODUCTION: Prognosis of prostate cancer depends on the risk stratification. D'Amico classification, the most commonly used risk stratification method is based on three factors, i.e., prostate specific antigen (PSA), Gleason grade and clinical stage. The impact of presence of multiple risk factors on prognosis after radical prostatectomy has not been studied in Indian patients. We analyzed the outcome of patients with high-risk disease undergoing robotic-assisted radical prostatectomy (RARP), as per D'Amico classification. MATERIALS AND METHODS: Our study is a review of the data of all patients with high-risk prostate cancer who underwent RARP between July 2010 and January 2015. Preoperative, perioperative and outcome data were analyzed for patients with high-risk disease as per D'Amico classification. RESULTS: Of 227 patients who underwent RARP, 90 (39.6%) were in the high-risk group. PSA > 20 ng/ml was the most common risk factor, present in 50 (55.6%) patients. All three risk factors were present in 3 patients, and single risk factor was present in 65 patients. Nine (10%) patients had lymphnode involvement, 18 (20%) had positive margin, and 38 (41.1%) had extraprostatic extension (EPE). Among these adverse outcomes, only EPE showed significant association with multiplicity of risk factors. At 12 months, 27.8% had biochemical recurrence (BCR). 92% of patients were continent at 12 months. CONCLUSION: About 92% of patients with high-risk disease were continent at 12 months, whereas less than one-third of the patients had BCR. EPE was the only outcome associated with multiplicity of risk factors. Adjuvant treatment is not required in two-thirds of patients.

A hospital based study on reference range of serum prostate specific antigen levels.

BACKGROUND & OBJECTIVES: Serum prostate specific antigen (PSA) levels are known to vary with race and ethnicity, environmental factors, lifestyle, metabolic and physiologic changes and advancing age. This study was designed to determine age specific serum PSA level in healthy Indian men and its comparison with that reported in different populations of the world. METHODS: A total of 1300 adult men who attended Executive Health Check-up programme in a tertiary care hospital in Haryana, India, were included in the study. Forty seven men were excluded from the analysis because of urological conditions affecting PSA values. Overall, 1253 men were analyzed for age specific PSA values. RESULTS: The age specific reference range of serum PSA values was 0.71 ng/ml in those younger than 40 yr; 0.85 ng/ml in 40-49 yr; 1.13 ng/ml in 50-59 yr group; 1.45 ng/ml in 60-69 yr group; 1.84 ng/ml in 70-79 yr group and 2.35 ng/ml in men older than 80 yr. INTERPRETATION & CONCLUSIONS: Our study provided the age-specific reference range of serum PSA in healthy men in India. The data suggested that the PSA levels were associated with increasing age.

Robertsonian translocation and their role in pathogenesis of recurrent in vitro fertilization failure.

BACKGROUND: Chromosomal anomalies have been postulated to be one of the principal genetic factors in reproductive failure. The principal structural anomalies are Robertsonian translocations which occur at a total frequency of rate 1.23 per thousand in newborns. Since most infertile men with Robertsonian translocation are oligospermic, they are good candidates for assisted reproduction like in vitro fertilization and intracytoplasmic sperm injection. However, a large number of such men/couples experience recurrent assisted procreation failure. MATERIAL/METHODS: The aim of the study was to diagnose the genetic basis of recurrent assisted reproductive failure (in vitro fertilization /intracytoplasmic sperm injection) in infertile men. One hundred twenty infertile men with idiopathic infertility who experienced recurrent assisted procreation techniques failure were recruited into this study after giving informed consent and after ethical clearance had been obtained. Semen and cytogenetic analyses were done to assess the semen status and cytogenetic profile of these men. RESULTS: Robertsonian translocations were found in 6 of 120 participants (5%). The men with Robertsonian translocation had recurrent assisted procreation techniques failure (>4 failed attempts; 3 in vitro fertilization and at least 1 unsuccessful intracytoplasmic sperm injection). In comparison, the men with a Yq microdeletion and other chromosomal abnormalities conceived after 1 to 2 in vitro fertilization cycles. These chromosomal anomalies may be the basis of failure of these assisted-reproductive procreation techniques. CONCLUSIONS: These results highlight the need for genetic investigations in all infertile men experiencing recurrent assisted procreation techniques failure.

Reconstructive bladder surgery in genitourinary tuberculosis.

Genitourinary tuberculosis (GUTB) occurs in 15-20% cases of pulmonary tuberculosis with a prevalence of 400 per 100,000 population. Reconstructive surgery for GUTB is required for cases with grossly distorted and dysfunctional anatomy that are unlikely to regress with chemotherapy alone. In the recent past, there has been a tremendous increase in the variety of reconstructive procedures for the urinary bladder, used in the management of GUTB. Augmentation cystoplasty includes the goals of increasing bladder capacity, while retaining as much of bladder as possible. Various bowel segments (from the stomach to the sigmoid colon) have been used for bladder reconstruction. The choice of material for reconstruction is purely the surgeon's prerogative--his skill, the ease, the mobility and length of mesentery (allowing bowel to reach the bladder neck without tension and maintaining an adequate blood supply). The presence or absence of concomitant reflux is of considerable importance. In the former, an ileocystoplasty with implantation of ureter to the proximal end of the isolated ileal loop and anastomosis of the distal end of the ileal loop to the bladder neck and trigone is advocated. In the latter case, the ureterovesical valve is preserved and colocystoplasty is preferred, wherein the sigmoid colon on being opened along its antimesentric border is joined to the trigone and bladder neck and then to itself to form a capacious pouch. Gastrocystoplasty reduces the risk of acidosis but is associated with complications like hypochloremic alkalosis and 'hematuria-dysuria' syndrome. Orthotopic neobladder reconstruction is a feasible option, suitable in cases of tubercular thimble bladder with a markedly reduced capacity (as little as 15 ml), where an augmentation alone may be associated with anastomatic narrowing or poor relief of symptoms. In this article, we review the various bladder reconstruction options used for the surgical management of GUTB, along with their indications and complications.

Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.

AIM: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). METHODS: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. RESULTS: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. CONCLUSION: Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.