Pre-operative risk factors associated with need for vasoepididymostomy at the time of vasectomy reversal.

The absence of sperm in the ejaculate after vasectomy reversal is commonly caused by failure to recognize and subsequently bypass epididymal or proximal vasal obstruction at the time of vasectomy reversal. If intra-operative proximal obstruction is suspected, vasoepididymostomy (VE) is recommended rather than vasovasostomy (VV). We sought to calculate the associated risk of needing VE, rather than VV with time from original vasectomy (obstructive interval) using a large cohort of vasectomy reversal patients. We reviewed the electronic and paper vasectomy reversal database by a single surgeon from 1978 through 2012. We performed univariate analysis to identify variables that predicted the need for VE rather than VV, and then combined only significant univariates into our multi-variable analysis. 2697 total men underwent vasectomy reversal, and 239 were repeat procedures. Of the 5296 individual testes operated on, 1029 were VE. Significant variables that predicted the need for VE on univariate analysis included: age, obstructive time interval, vasectomy reversal after previous VV (repeat vasectomy reversal), and year the procedure was performed. On multi-variable analysis significant risk factors for VE were age above 50 (OR 1.36), repeat vasectomy reversal (OR 5.78), and greater obstructive time interval (OR 1.56). For every 3 years since original vasectomy, the risk of needing VE increases by 56%. There is a linear relationship between obstructive interval and need for VE. Men undergoing repeat vasectomy reversal have five times greater risk of requiring VE and men greater than 50 years of age are also at higher risk. Using these pre-operative predictors is helpful in identifying patients who will benefit from referral to an experienced surgeon who can perform VE.

The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile men.

Our objective was to evaluate the safety and efficacy of clomiphene citrate (CC) in infertile and hypoandrogenic men through a retrospective study between September 2013 and May 2014. We identified 47 men between 18 and 55 years placed on 50 mg CC every other day. We evaluated the effect of CC on testosterone after 2 weeks, rates of adverse effects and predictors of CC response. Mean baseline testosterone, bioavailable testosterone and estradiol were 246.8 ng dl(-1), 125.5 ng dl(-1) and 20.8 pg dl(-1), respectively. At 2 weeks, mean testosterone, bioavailable testosterone and estradiol increased to 527.6 ng dl(-1), 281.8 ng dl(-1) and 32.0 pg dl(-1) (all P<0.001). Two patients at 2 weeks and one patient at 3 months had a paradoxical decrease in testosterone. Mean total motile count (TMC) and concentration increased from 59.7 million (s.e.m.: 16.5) and 50.7 millions ml(-1) (s.e.m.: 11.1) at baseline to 90.9 million (s.e.m.: 25.9) and 72.5 millions ml(-1) (s.e.m.: 17.5), respectively, at 3 months, although this was nonsignificant (P=0.09, 0.09). No patient on CC experienced a paradoxical decrease in TMC or sperm concentration. On age-adjusted regression analysis, age, BMI, longitudinal testis axis, baseline follicle-stimulating hormone, LH and estradiol did not correlate with improvement in bioavailable testosterone at 2 weeks. CC improves testosterone and may improve semen parameters, although a small percentage of men may not demonstrate improvement in testosterone.

A new minimally invasive open pelvic lymphadenectomy surgical technique for the staging of prostate cancer.

We report a new method for lymphadenectomy, the minilaparotomy (inguinal) pelvic lymph node dissection (MLPLND), and compare it with laparoscopic pelvic lymph node dissection (LPLND) in terms of cost, effectiveness, operation time and morbidity. We reviewed a series of 111 consecutive patients: 51 had MLPLND and 60 had LPLND. All patients had proved adenocarcinoma of the prostate by biopsy. Of the MLPLND patients, only 1 had to stay overnight in the hospital, and all left within 24 hours. Pelvic lymphadenectomy consisted of nodal removal along the internal iliac vessels and the external iliac vein, and nodes of the obturator foramen. A total of 14% of the patients had disease involving the lymph nodes. The cost of MLPLND was 50% of the cost of LPLND, with no interoperative or postoperative morbidity. This new operation can be performed thoroughly an inexpensively in approximately 35 minutes, with little or no morbidity. Since the drawbacks of laparoscopic techniques associated with instrument costs and the learning curve for this technically difficult operation are eliminated, staging pelvic lymphadenectomy can be performed routinely on a wider variety of patients with potential metastatic disease. Currently, we recommend MLPLND to any patient with a tumor of Gleason score 7 or higher or a serum prostate-specific antigen value of 15 ng/mL or higher.

Direct observation of endocytosis of gastrin releasing peptide and its receptor.

Endocytosis of the gastrin releasing peptide receptor (GRP-R) may regulate cellular responses to GRP. We observed endocytosis in transfected epithelial cells by confocal microscopy using cyanine 3-GRP (cyanine 3.18-labeled gastrin releasing peptide) and GRP-R antibodies. At 4 degrees C, cy3-GRP and GRP-R were confined to the plasma membrane. After 5 min at 37 degrees C, ligand and receptor were internalized into early endosomes with fluorescein isothiocyanate-transferrin. After 10 min, cy3-GRP and GRP-R were in perinuclear vesicles, and at 60 min cy3-GRP was in large, central vesicles, while GRP-R was at the cell surface. We quantified surface GRP-R using an antibody to an extracellular epitope and an 125I-labeled secondary antibody. After exposure to GRP, there was a loss and subsequent recovery of surface GRP-R. Recovery was unaffected by cycloheximide, and thus independent of new protein synthesis, but was attenuated by acidotropic agents, and therefore required endosomal acidification. Internalization of 125I-GRP, assessed using an acid wash, was maximal after 10-20 min, and was clathrin-mediated since it was inhibited by hyperosmolar sucrose and phenylarsine oxide. Thus, GRP and its receptor are rapidly internalized into early endosomes and then dissociate in an acidified compartment. GRP is probably degraded whereas the GRP-R recycles.