Penile transplantation: the US experience and institutional program set-up.

Penile transplantation using vascularized composite allografts is an emerging technique to treat genital loss. In the United States, this procedure has been performed successfully at Massachusetts General Hospital in a patient who had previously undergone treatment for penile cancer. The Johns Hopkins Medical Institutions has developed a research protocol to perform penile transplantation in patients with genital loss secondary to trauma. The process of selecting the appropriate candidate for genitourinary (GU) vascularized composite allograft surgery is rigorous including extensive physical examination, laboratory testing, imaging and psychological evaluations. After transplantation, limiting the potential complications associated with immunosuppression is critical given that the procedure is intended to improve quality of life and is not life-saving. Ultimately, penile transplant is a surgical intervention which may have numerous applications. Optimization of the pre-operative screening process, surgical technique, and immunosuppressive protocol is required to establish this method as the standard treatment for patients with genital loss and limited reconstructive options.

Different Management Options for Transplant Ureteral Obstructions within an Inguinal Hernia.

Ureteral obstruction secondary to an inguinal hernia with transplant ureteral component is an extremely rare entity with only several case reports found in literature. In all previously reported cases, management of the obstruction involved temporary drainage with ureteral stenting or nephrostomy tube placements followed by delayed definitive repair. We present two case reports, here one being the first one managed by immediate definitive repair via ureteral reimplant and herniorrhaphy and a second case by delayed definitive repair after percutaneous nephrostomy tube placement. Both patients continued to do well postoperatively with normalization of renal function on follow-up.

Death receptor 5 agonist TRA8 in combination with the bisphosphonate zoledronic acid attenuated the growth of breast cancer metastasis.

INTRODUCTION: Bone metastasis affects the majority of patients with advanced breast cancer and no adequate therapy exists. Bisphosphonates, like zoledronic acid, inhibit the osteolytic component of tumor growth in osseous tissues, but these drugs are not curative. The current study evaluated the combination of zoledronic acid with death receptor 5 agonists in an animal model of breast cancer bone metastasis. MATERIALS AND METHODS: Female athymic nude mice (age 4-6 weeks, n=35) were inoculated with 200,000 luciferase-positive MDA- MB-435 cells by injection into the left ventricle. Animals were immediately imaged by bioluminescence technique and placed into one of the following therapy groups: Saline, hTRA8, hTRA8 + zoledronic acid, mTRA8, mTRA8 + zoledronic acid, or zoledronic acid monotherapy. DR5 agonists were given at 200 microg/dose and zoledronic acid 5 microg/dose, with mice treated biweekly for 4.5 weeks and imaged weekly. RESULTS: Combination therapy containing either hTRA8 or mTRA8 with zoledronic acid significantly reduced the number of secondary lesions (7.67+2.2 and 7.5+1.7 lesions/mouse, respectively) compared to saline treated controls (12.1+/-1.56 lesions/mouse) as assessed by bioluminescence imaging (p<0.05). Additionally, monotherapy with hTRA8 resulted in a significant reduction in tumor number (8.3 +/- 2.9) compared to control animals. Total body tumor burden over time were significantly less in groups treated with hTRA8+zoledronic and mTRA8 + Zoledronic acid combination as compared with the saline control group. At day 33, both combination therapies and zoledronic acid monotherapy provided significant reduction in total tumor burden and tumor infiltration of hindlimbs by histomorphometry (p<0.05). CONCLUSION: DR5 agonists in combination with bisphosphonates may be an acceptable combination therapy to reduce breast cancer growth in bone.

Noninvasive bioluminescence imaging in small animals.

There has been a rapid growth of bioluminescence imaging applications in small animal models in recent years, propelled by the availability of instruments, analysis software, reagents, and creative approaches to apply the technology in molecular imaging. Advantages include the sensitivity of the technique as well as its efficiency, relatively low cost, and versatility. Bioluminescence imaging is accomplished by sensitive detection of light emitted following chemical reaction of the luciferase enzyme with its substrate. Most imaging systems provide 2-dimensional (2D) information in rodents, showing the locations and intensity of light emitted from the animal in pseudo-color scaling. A 3-dimensional (3D) capability for bioluminescence imaging is now available, but is more expensive and less efficient; other disadvantages include the requirement for genetically encoded luciferase, the injection of the substrate to enable light emission, and the dependence of light signal on tissue depth. All of these problems make it unlikely that the method will be extended to human studies. However, in small animal models, bioluminescence imaging is now routinely applied to serially detect the location and burden of xenografted tumors, or identify and measure the number of immune or stem cells after an adoptive transfer. Bioluminescence imaging also makes it possible to track the relative amounts and locations of bacteria, viruses, and other pathogens over time. Specialized applications of bioluminescence also follow tissue-specific luciferase expression in transgenic mice, and monitor biological processes such as signaling or protein interactions in real time. In summary, bioluminescence imaging has become an important component of biomedical research that will continue in the future.