The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSC) and tolerogenic CD8+/TCR− graft facilitating cells (FC) combined with nonmyeloablative conditioning that allows engraftment, durable chimerism, and tolerance induction in highly mismatched related and unrelated donor-recipient pairs. Eight recipients of HLA-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200 cGy total body irradiation, and cyclophosphamide followed by post-transplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from 5 of 6 related to 1 of 6 unrelated. The absolute neutrophil counts nadired approximately one week after transplant, with recovery by two weeks. Multilineage chimerism at one month was 6% to 100%. The conditioning was well tolerated with outpatient management after postoperative day two. Two subjects exhibited transient chimerism and have been reduced to low-dose tacrolimus monotherapy. One subject developed viral sepsis two months after transplant and experienced renal artery thrombosis. Five subjects have durable chimerism, with immunocompetence and donor-specific tolerance by in vitro proliferative assays and were successfully weaned off all immunosuppression one year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.
Minimally invasive hepatic surgery has become a viable alternative to open hepatic surgery. Our present data are equivalent or superior to those encountered in any large open series. Our experience with RFA confirms a low local recurrence rate and an excellent technique for bridging patients to transplantation. Morbidity and mortality rates for minimally invasive hepatic resections in cirrhotics, is similar to other reported open resection series. This series confirmed excellent interim survival rates after laparoscopic HR and superiority over RFA in the treatment of cancer, with significantly lower local tumor recurrence rate.
Although West Nile fever is mild in the vast majority of infected persons, there is growing evidence that the disease may be more severe in the immunocompromised population. We describe 3 recipients of kidney or pancreas transplants who developed West Nile fever, 2 of whom had meningoencephalitis. As is the norm when treating serious infections in transplant recipients, a reduction of immunosuppression was pursued for these patients. Despite the severe nature of the disease in 2 patients, all recovered from the disease. The time course of neurologic recovery in the 2 patients with meningoencephalitis is highlighted. We also review the literature on West Nile fever in organ transplant recipients. In areas where West Nile virus is endemic, one must have a high index of suspicion for the illness when dealing with fever in transplant recipients.
Left hepatic trisectionectomy remains a challenging procedure. Preoperative obstructive jaundice considerably increases perioperative risk. Concomitant partial resection of the remaining liver appears to be safe and offers the potential for cure in patients with colorectal metastasis affecting all liver segments.
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