Successful in vivo tumor targeting of prostate-specific membrane antigen with a highly efficient J591/PEI/DNA molecular conjugate.

We have utilized a novel polyethylenimine (PEI)/DNA-betagal vector to investigate the specificity and efficiency of immuno-targeting prostate-specific membrane antigen (PSMA). Coupling of the PSMA-specific monoclonal antibody, J591, to the vector was facilitated via the high-affinity interaction between phenyl(di)boronic acid and salicylhydroxamic acid molecules. Highly efficient gene delivery by this prostate cancer (PCA)-targeted J591/polyethylene glycol (PEG)/PEI/DNA-betagal vector was demonstrated in PSMA-positive cells relative to controls, resulting in significant growth inhibition in vitro when the J591/PEG/PEI/DNA-p53 was used. Competition with free antibody resulted in about 90% reduction in both J591 internalization and betagal gene delivery, indicating specificity for PSMA-positive cells. More importantly, testing the efficiency of the J591/PEG/PEI/DNA-betagal targeting vector in an orthotopic PCA model in nude mice resulted in up to a 20-fold increase in gene delivery over the untargeted vector controls. The in vivo organ distribution profile also revealed betagal expression predominantly in the tumor, which was more than 1 log higher than the next highest level of expression in the lung. Furthermore, with the targeted vector containing the gene for yellow fluorescent protein or biotinylated J591, we further demonstrate in vivo that vector-mediated gene delivery is specific for both tumor cells and tumor-associated neovasculature in PSMA-positive tumors. These results suggest the potential for further optimization of this novel vector in the context of therapeutic gene delivery.

Laparoscopic colposuspension with a transvaginal illuminator.

A series of 63 women with anatomic stress urinary incontinence were treated at two institutions by laparoscopic urethrovesical suspension with vaginal transillumination of the paraurethral endopelvic fascia to facilitate laparoscopic dissection and ligature carrier and suture needle placement. In no case did illumination-assisted suture placement require suture removal or replacement for inadequate or traumatic placement within the bladder, or was it associated with hemorrhage. At a minimum of 2 years' follow-up, there were six treatment failures. The reusable illuminator enhances visual contrast between the pelvic floor and bladder neck for laparoscopic dissection and paraurethral needle placement. It also provides an effective backstop to the needle, eliminates needle injuries to operators' fingers during suturing, stabilizes the endopelvic fascia during dissection, and increases visual contrast between the bladder neck and adjacent endopelvic fascia.

Laparoscopic bladder neck suspension.

STUDY OBJECTIVE: To determine the results of transperitoneal laparoscopic bladder neck suspension. DESIGN: Prospective observational study. SETTING: A university-affiliated hospital. PATIENTS: Thirty-two consecutive women with the diagnosis of genuine stress incontinence and hypermobile proximal urethra and bladder neck. INTERVENTIONS: Laparoscopic transperitoneal bladder neck suspension (Burch procedure) in combination with laparoscopic-assisted vaginal hysterectomy or other procedures. MEASUREMENTS AND MAIN RESULTS: Success was defined as lack of leakage of urine, negative Q-Tip test, and good voiding control without need for drugs 6 weeks postoperatively. Over a minimum follow-up of 24 months, the procedure yielded satisfactory urethrovesical support in all patients and an overall success rate of 90.6%. CONCLUSIONS: Laparoscopic transperitoneal bladder neck suspension (Burch procedure) is an excellent endoscopic technique for the surgical treatment of genuine stress incontinence, although it awaits the test of time.

Sacrospinous Ligament Fixation Simplified with a New Endoscopic Suturing Device

This study evaluated the effectiveness of the EndoStitch during sacrospinous ligament fixation in 28 women, in combination with correction of other pelvic floor disorders. Application and retrieval of Surgidac (a coated and braided polyester suture) were performed in under 5 minutes without any complications. The patients were followed in terms of vaginal vault support, vaginal length, vaginal axis deviation, sexual discomfort when applicable, and bladder or rectal dysfunction. There was one failure. The technique was easy, safe, and easy to teach.

Epidermal growth factor and basic fibroblast growth factor in peritoneal fluid of women with endometriosis.

OBJECTIVE: To determine and compare the concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (FGF) in the peritoneal fluid of women with and without endometriosis. DESIGN: Prospective study. SETTING: Tertiary care center affiliated with university medical school. PATIENTS: Forty-two women with endometriosis and 34 women without endometriosis confirmed by laparoscopy. MAIN OUTCOME MEASURES: Epidermal growth factor and basic FGF concentrations were determined by highly sensitive enzyme immunoassays using monoclonal antibodies. RESULT: Approximately 50% of the PF samples had EGF concentrations of > 0.4 pg/mL (conversion factor to SI unit, 0.17) and 90% had basic FGF concentrations of > 1 pg/mL (conversion factor to SI unit, 0.058). Concentrations of EGF or basic FGF in PF did not differ significantly between the two groups. In normal women, there was a significant correlation between EGF and basic FGF during the luteal phase. In women with endometriosis, EGF levels were higher during the luteal phase, but there was no correlation of either EGF or basic FGF levels with the severity of endometriosis. CONCLUSIONS: The concentrations of EGF and basic FGF were highly variable in the PF of women with or without endometriosis and did not differ significantly. The concentrations were so low that neither EGF nor basic FGF in PF could bind to its receptor.

Comparative study of laparoscopic oophorectomy.

STUDY OBJECTIVE: To determine the differences between laparoscopic oophorectomies and oophorectomies performed by laparotomy with respect to total hospital cost, length of hospital stay, and operative time. DESIGN: A prospective analysis of all women who underwent one of these procedures from January 1, 1992, to December 31, 1992. SETTING: A university-affiliated hospital. PATIENTS: Fifty-seven women requiring surgery for the management of pelvic pain, adnexal masses, or endometriosis. INTERVENTIONS: Twenty-six women underwent laparoscopic surgery and 31 had laparotomy. MEASUREMENTS AND MAIN RESULTS: The results for laparoscopy and laparotomy, respectively, were as follows: mean hospital cost $6139 versus $7053 (p = 0.02); hospital stay 1.07 versus 3.87 days (p = 0. 00); and mean operative time 175.23 versus 136.94 minutes (p = 0. 003). No woman had a serious complication, and none in the laparoscopy group required a laparotomy. CONCLUSION: Laparoscopic oophorectomy is a safe, highly successful, and cost-effective procedure, although it is associated with a longer operative time than laparotomy.

Comparative Study in Laparoscopic Oophorectomy

This study was undertaken to determine differences between laparoscopic oophorectomies and oophorectomies performed through a laparotomy in terms of total hospital cost, hospital length of stay, and operative time. From January 1, 1992 to December 31,1992, all patients (57) who had undergone oophorectomies in our hospital were included in the study. Twenty-six of these procedures were laparoscopic. The laparoscopy group had a mean hospital cost of $6,139.00 vs. $7,053.00 for the laparotomy group, a statistically significant difference. The hospital stay for the laparoscopy group was a mean of 1.07 days vs. 3.87 days for the laparotomy group, which was also statistically significant. Operative time for the laparoscopy group was a mean of 175.23 minutes vs. 136.94 minutes for the laparotomy group. This is statistically significant. None of the 57 women had a serious complication. This study demonstrates that laparoscopic oophorectomy is a safe, highly successful, and cost-effective procedure. However, our results indicate that laparoscopic oophorectomy is associated with longer operative times as compared with laparotomy.