Penis Transplantation: First US Experience.

OBJECTIVE: We describe the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND: Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 penis transplants have been performed worldwide. METHODS: After institutional review board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by a multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After appropriate donor identification and recipient induction with antithymocyte globulin, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a donor skin pedicle as the composite allograft. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS: Intraoperative, the allograft had excellent capillary refill and strong Doppler signals after revascularization. Operative reinterventions on postoperative days (PODs) 2 and 13 were required for hematoma evacuation and skin eschar debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff I), progressed by POD 32 (Banff III), and required a repeat course of methylprednisolone and antithymocyte globulin. At 7 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. CONCLUSIONS: We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our successful penile transplantation pilot experience represents a proof of concept for an evolution in reconstructive transplantation.

Genitourinary vascularized composite allotransplantation.

PURPOSE OF REVIEW: Genitourinary vascularized allotransplantation (GUVCA) is gaining interest as a treatment option for patients with functional and aesthetic urogenital tissue loss. Only three cases have been done worldwide and research on the implementation and feasibility of this procedure is in an elementary state. RECENT FINDINGS: The psychosocial impact and ethical considerations with GUVCA are remote, particularly because of the intimate and personal nature of genital tissue. Though two of the three penile transplantation cases are considered successful, various unexpected factors and complications have been described alongside these successes. Treatment outcome depends on a complex combination of immunological, technical, and psychosocial components that will be different per individual case. Multidisciplinary evaluation and treatment protocols should be established to ensure that the quality of life in GUVCA recipients can be increased in a safe and ethical way. SUMMARY: Penile transplantation represents challenging new potential to improve phallus reconstruction in patients with severe genital tissue defects, but worldwide experience with GUVCA is limited. Controlled multicenter research is required to better define the risk/benefit ratio of this experimental yet promising treatment option.

Tolerance of a Vascularized Composite Allograft Achieved in MHC Class-I-mismatch Swine via Mixed Chimerism.

Background: Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be fully-MHC-mismatched (in contrast to living-related renal transplant donor-recipient pairs matched at one MHC haplotype). After achieving VCA tolerance in a swine model equivalent to clinical living-related renal transplants (single-haplotype MHC mismatches: e.g., "mother-daughter"/haploidentical), we tested our protocol in MHC class I, class II, and fully-MHC-mismatched pairs. Although class II mismatched swine demonstrated similar results as the haploidentical scenario (stable mixed chimerism and tolerance), our protocol failed to prevent rejection of class I and full mismatch VCAs. Here, we describe a new adapted conditioning protocol that successfully achieved tolerance across MHC class-I-mismatch barriers in swine. Methods: Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept®) and anti-IL6R mAb (Tociluzimab®) and were transplanted with an osteomyocutaneous VCA from the same donor. Results: Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4-CD8- T cells producing IL-10. Conclusions: This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol.

Avascular Necrosis of the Scaphoid Preiser Disease.

No consensus regarding optimal treatment or etiology of Preiser disease exists. We described the epidemiology, classification and treatment characteristics of 18 patients with Preiser disease. Patients with changes related to previous trauma, and without radiographs were excluded. Based on the radiographs at diagnosis, we classified 13 scaphoids as Herbert Lanzetta stage II, four as stage III, and one as stage IV. In 12 patients nonspecific treatment was offered and only two patients received surgical treatment. We found that chosen treatment is not associated with the severity of Herbert Lanzetta stage and the outcome is not influenced by chosen treatment.

Toward Development of the Delayed Tolerance Induction Protocol for Vascularized Composite Allografts in Nonhuman Primates.

BACKGROUND: Transplantation of vascularized composite allografts is limited mainly by the need for life-long immunosuppression. The consequent side effects and looming specter of chronic rejection portend eventual allograft loss. Development of tolerogenic protocols is thus of utmost importance to the field of vascularized composite allograft transplantation. METHODS: With a modified delayed tolerance induction protocol, 10 cynomolgus macaques received hand (n = 2) or face vascularized composite allografts across both full and haploidentical major histocompatibility complex barriers before donor bone marrow transplantation at a later date. Protocol and for-cause allograft skin biopsies were performed for immunohistochemical analysis and analysis of donor-recipient leukocyte contribution; mixed chimerism in peripheral blood and in vitro immune responses were assessed serially. RESULTS: Before bone marrow transplantation, maintenance immunosuppression for 4 months led to lethal complications, including posttransplant lymphoproliferative disorder (in two of four recipients), which necessitated early study termination. Shortening the maintenance period to 2 months was clinically relevant and allowed all subsequent subjects (n = 6) to complete the delayed tolerance induction protocol. Acute rejection developed within the first 2 to 4 weeks after transplantation, with corresponding near-complete turnover of allograft leukocytes from donor to recipient origin, but donor-specific antibodies remained negative. After bone marrow transplantation, mixed chimerism failed to develop, although carboxyfluorescein succinimidyl ester mixed lymphocyte reaction demonstrated generalized unresponsiveness. However, the accrual of subsequent rejection episodes eventually culminated in graft vasculopathy and irreversible allograft loss. CONCLUSIONS: Despite the various advantages of the delayed tolerance induction protocol, it failed to reliably induce mixed chimerism and thus immunologic tolerance to vascularized composite allografts, given currently available immunosuppression treatment options. Ongoing work shows promise in overcoming these limitations.

Unplanned Operations and Adverse Events after Surgery for Diaphyseal Fracture of the Clavicle.

BACKGROUND: We used a database of patients treated at three hospitals to study the primary null hypothesis that there are no factors associated with unplanned reoperations or adverse events after surgical repair for diaphyseal clavicle fracture. Additionally we addressed the following secondary study questions: 1. What is the prevalence of unplanned reoperations or adverse events after surgical repair for diaphyseal clavicle fracture? 2. Is early implant loosening or breakage after surgical repair for diaphyseal clavicle fracture related to fixation type? 3. Is the type of fixation associated with the prevalence of brachial plexus palsy after surgical repair of a diaphyseal clavicle fracture? METHODS: We retrospectively analyzed 249 adult patients who had surgery for a diaphyseal clavicle fracture to determine factors associated with unplanned reoperations or adverse events. Thirty-two patients (13%) had at least one unplanned reoperation or adverse event. Four of 249 patients (1.6%) developed early implant loosening or breakage. Patients that had local implant irritation, planned implant removal, or sensory symptoms thought to be due to nerve irritation were not included in the reported unplanned reoperations or adverse event rate. RESULTS: Only female sex was associated with unplanned reoperations or adverse events after surgery for diaphyseal clavicle fracture. No other patient, technical, or injury related factors tested in this study were associated with unplanned reoperations or adverse events. CONCLUSION: Patients that have surgery for diaphyseal clavicle fracture have an approximately 13% risk of an unplanned second surgery or an adverse event. Women can be counseled that they are three times as likely as men to have an unplanned reoperations or adverse event.

What Predicts Outstanding Orthopedic Residents among the Program?

BACKGROUND: An oversupply of qualified applicants leads to intense competition for the limited number of first year orthopedic residency positions. Therefore, program directors can be more selective in choosing their future residents. However, it is unclear if there are resident characteristics that correspond with trainee performance. METHODS: We asked (1) what resident characteristics are associated with subjective residency performance score? and (2) what resident characteristics are associated with Orthopedic In-Training Examination (OITE) score?A total of 119 orthopedic residents accepted at the Harvard Combined Orthopedic Residency Program from 1999 - 2009 were included in this study. The current program director together with two former program directors in the selected time period defined the subjective residency performance score based on the clinical skills of the residents during training. RESULTS: Former Olympic or varsity athlete (P=0.018) and Alpha Omega Alpha (AOA) status (P=0.014) were associated with a better subjective residency performance score. Higher USMLE step 1 score (P=0.0038), known person within faculty prior to the residency (did a research rotation, or local medical student) (P=0.041), and AOA (P=0.015) status were associated with a higher OITE score. CONCLUSION: AOA status of the applicant for orthopedic residency is associated with both a higher OITE score and a better subjective residency performance score.