Francisco G. Cigarroa

Steroid elimination 24 hours after liver transplantation using daclizumab, tacrolimus, and wcophenolate mofetil

BACKGROUND Corticosteroids have long been a cornerstone of orthotopic liver transplant (OLTx) immunosuppression. Newer, more potent, agents have successfully allowed for more rapid tapering and discontinuation of corticosteroids in OLTx recipients. We hypothesize that corticosteroids can be safely avoided after the first postoperative day (POD) using these newer agents. METHODS Thirty adult OLTx recipients were prospectively enrolled in a randomized open-label, institutional review board-approved protocol. Fifteen patients (group A) received our standard regimen of tacrolimus, mycophenolate mofetil, and corticosteroids, and 15 patients (group B) received daclizumab, 2 mg/kg on POD 0 and 14, with tacrolimus, mycophenolate mofetil, and corticosteroids on POD 0 and 1 and then discontinuation. In both groups, mycophenolate mofetil was tapered off between 3 and 4 months after OLTx. Bone mineral densitometry was performed at 1, 3, and 6 months after OLTx. Quantitative hepatitis C virus (HCV) polymerase chain reaction was obtained at days 0, 7, 14, 21, and 28. Retransplant recipients, patients with autoimmune hepatitis, or status 1 or 2A patients were excluded. RESULTS Patient and graft survival rates were 93% (group A) and 100% (group B) with mean follow-up of 18 months. Patients in group B had more rejection diagnosed (25%) compared with group A (6.7%). Yet, the incidence of biopsy-proven acute rejection requiring steroid therapy was 6.7% in both groups. Hispanic race was common in groups A and B (87% and 74%). A total of six biopsies were performed in group B, with three patients having mild rejection responding to an increase in tacrolimus without the need for corticosteroids. One patient in group B was switched to cyclosporine for severe neurotoxicity and remains on monotherapy with normal graft function. No patient in either group developed a requirement for additional antihypertensive medication. Likewise, there were no patients with new-onset diabetes. The bone mineral densitometry was higher in group B at every time point but did not reach statistical significance. Serum cholesterol level was significantly (P=0.03) lower in group B at 6 months after OLTx. Serum triglycerides were also lower, but the difference was not significant. Quantitative polymerase chain reaction for HCV-positive patients (group A, n=7; group B, n=8) frequently increased after OLTx. There was no correlative decrease associated with daclizumab. At present, two patients in group A have documented HCV recurrence. CONCLUSION Corticosteroids can be safely avoided after POD 1 with the current regimen. With early follow-up, there is no difference in hypertension or diabetes or bone density. Lipid panels tended to be lower in patients who were not on corticosteroids. Longer term follow-up will be needed to demonstrate the potential advantage of corticosteroid avoidance in regard to hypertension, diabetes, and possibly HCV recurrence.

Liver transplantation in infants younger than 1 year of age.

OBJECTIVE The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults.

Transplantation of single and paired pediatric kidneys into adult recipients

BACKGROUND The transplantation of kidneys from cadaveric donors < or = 5 years of age into adult recipients is controversial. The large disparity between donor renal mass and recipient body mass is feared to be problematic. Controversy also exists whether to transplant kidneys from these young donors individually or as a pair into a single recipient. STUDY DESIGN We retrospectively reviewed our experience from January 1991 to January 1995 with 22 adult renal transplantations using kidneys from cadaveric donors < or = 5 years of age. Ten patients received single allografts. Twelve received organs paired en bloc. Fifty-two adult recipients from cadaveric donors aged 18-55 years served as controls. All patients received cyclosporine-based immunosuppression. Recipient characteristics did not differ significantly between the groups. RESULTS Actuarial patient and graft survival rates were similar for the two groups. The incidence of urinary complications was higher in the recipients of pediatric kidneys than in the adult-donor group (18.2% versus 3.8%, respectively, p = not significant). No grafts were lost from urinary complications. Renal function, as determined by the calculated creatinine clearance, was significantly greater in the pediatric group (76.1 +/- 4.0 versus 61.4 +/- 23.2 mL/min, p = 0.035) by 6 months after transplantation. Recipients of paired pediatric kidneys initially had better renal function (63.9 +/- 21.4 mL/min) than those receiving single pediatric kidneys (38.2 +/- 11.6 mL/min) (p = 0.004), but by 6 months, no significant difference existed. At 2 years, renal function in the pediatric-donor group remained significantly better than in the adult-donor group. Hematocrit levels as a measure of erythropoiesis were similar for single pediatric, paired pediatric, and adult-donor recipients. CONCLUSIONS Kidneys from cadaveric donors < or = 5 years of age are suitable for transplantation into adults. Pediatric kidneys provide excellent renal function despite an initially tremendous disparity between renal mass and recipient body mass. Rapid true renal growth probably occurs. No appreciable advantage is achieved by using two pediatric kidneys for a single recipient.

Radiofrequency tissue ablation: Effect of hepatic blood flow occlusion on thermal injuries produced in cirrhotic livers

AbstractBackground: Radiofrequency thermal ablation has been used as a treatment for several types of hepatic malignancies. Many of these lesions exist in the presence of cirrhosis. Limitations exist to the size of the ablations and, subsequently, the efficacy of treatment. Hepatic vascular inflow occlusion has been advocated as an adjunctive measure to increase the efficacy of the ablation. We present a model in the human cirrhotic liver that demonstrates the advantage of blood flow occlusion during radiofrequency ablation. Methods: Five patients with advanced endstage liver disease scheduled to have orthotopic liver transplantation were enrolled in this study. After laparotomy and before hepatectomy, radiofrequency ablation was performed without and with hepatic blood flow occlusion. After hepatectomy, the liver was sectioned, the area of ablation was measured in three dimensions, and the volume of ablation calculated. Results: Three of the patients had had previously placed transjugular intrahepatic portosystemic shunt. The mean volume of the ablation without blood flow occlusion was 22.5 ± 7.4 cm3 and that with blood flow occlusion was 48.4 ± 24.0 cm3 (P = .05). Conclusions: Ablation area is increased significantly with hepatic blood flow occlusion in the human cirrhotic liver. This result may have application in the treatment of larger (>3 cm) hepatic malignancies.

Recombinant Human Mullerian Inhibiting Substance Inhibits Epidermal Growth Factor Receptor Tyrosine Kinase

Autophosphorylation of the epidermal growth factor (EGF) receptor in A-431 cells and plasma membrane fractions was inhibited by partially purified recombinant human Müllerian Inhibiting Substance (MIS). Immunoprecipitation of the EFG receptor using anti-EGF receptor or anti-phosphotyrosine antibodies, and phosphoamino acid analysis of this receptor, demonstrated that MIS specifically inhibited EGF-induced tyrosine phosphorylation. Inhibition of EGF receptor autophosphorylation by MIS in membrane preparations was not affected by increasing concentrations of EGF, manganese or [gamma-(32)P] ATP. Thus, it is unlikely that MIS competes for EGF binding sites or sequesters substrate. Immunoabsorption of MIS with anti-human MIS antibody blocked the MIS inhibition of EGF receptor autophosphorylation, indicating that the inhibition was due to MIS. Our data suggest that MIS regulates the activity of the EGF receptor tyrosine kinase in A-431 cells.

Outcome of liver transplantation in Hispanics versus non-Hispanics: Is there a difference?

IN THE PAST DECADE 10% of orthotopic liver transplant (OLT) recipients in the United States have been of Hispanic origin. Little has been reported regarding OLT outcomes in reference to recipient ethnic origin. Differences in outcome have been shown in renal transplant graft survival of African-American recipients when compared to Caucasians. Differences in outcome of other organ transplants relative to ethnicity have never been clearly proven. At our center more than 50% of OLT recipients are from Hispanic origin, and it is of our particular interest to establish any ethnic difference in graft or patient survival if present. To determine the differences in outcome of the Hispanic (H) group versus the non-Hispanic group (NH), we analyzed our experience for the past 5 years.

Tc-99m-labeled red blood cell scanning localizes anastomotic hemorrhage between the distal ileum and duodenal stump of an enteric-drained pancreas transplant

Increasing numbers of pancreas transplants are performed with enteric exocrine drainage. Complications are more difficult to diagnose in enteric-drained pancreas transplants than in bladder-drained pancreas transplants. A 41-year-old woman underwent a simultaneous kidney-pancreas transplant. She received a whole-organ pancreas transplant with exocrine drainage from the duodenal stump into the distal ileum. One week after operation, accelerated renal rejection developed and was treated with plasmapheresis. In a coagulopathic state from plasmapheresis, marked hematochezia developed 2 weeks after operation. The Tc-99m-labeled red blood cell scan clearly identified anastomotic hemorrhage between the duodenal stump of the pancreas transplant and the ileum.

Imperforate anus with long but apparent low fistula in females

Despite the low entry of the rectum into the vagina in some females with imperforate anus, the fistula may be deceivingly long. This variation should alert the surgeon to measure the fistula prior to anoplasty. During surgery, biopsies of the mobilized segment should also be done to assure that cloacal-transitional lined structures have been removed and rectal mucosa anastamosed to the perineum.

Graft quality matters: Survival after simultaneous liver-kidney transplant according to KDPI

Poor renal function is associated with higher mortality after liver transplantation. Our aim was to understand the impact of kidney graft quality according to the kidney donor profile index (KDPI) score on survival after simultaneous liver‐kidney (SLK) transplantation.

Disparities in Live Donor Kidney Transplantation: Related to Poverty, Race, or Ethnicity?

Over the past 2 decades, increasing national and local attention has been placed on promoting increases in live donor kidney transplantation in the United States and in addressing existing racial/ethnic disparities in the rates of live donor transplantation. Still, a large gap exists between current realities and proposed goals. In this issue of JAMA, Purnell and colleagues1 reviewed national trends from 1995 to 2014 in the rates of live donor kidney transplantation according to racial/ethnic differences. The authors observed decreases in the cumulative incidence of live donor kidney transplantation for black and Hispanic patients, resulting in increasing disparities compared with white patients. These disparities are a topic of great importance. To accurately target solutions for the persistent disparities involving racial/ethnic minorities, it is incumbent to fully understand the multifaceted underlying issues related to live donor kidney transplantation. The study by Purnell and colleagues1 included 453 162 adult kidney transplantation candidates (mean age, 50.9 years; 39% were women; 48% were white; 30%, black; 16%, Hispanic; and 6%, Asian) of whom 59 516 (13.1%) ultimately received a live donor kidney transplantation. The authors found that the proportional incidence of live donor kidney transplantation among black and Hispanic patients was lower when comparing the rates in 2010-2014 vs 1995-1999. However, live donor kidney transplantation has not declined for these groups in terms of absolute numbers compared with the initial period studied. The greatest period of growth occurred from 1995 to 2009 when the volume of live donor kidney transplantation more than doubled for every racial/ ethnic group. The largest increases in live donor kidney transplantation were among Hispanic and Asian recipients, which increased by more than 2.6 times during this period according to the crude numbers of live donor kidney transplantations provided in Table 3 in the article.1 For example, the number of live donor kidney transplantation increased from 999 among Hispanic patients in 1995-1999 to 2628 in 2005-2009. Changes in cumulative incidence of live donor kidney transplantation as reported by the authors must be considered within the context of the overall increase in the denominator that represents patients on the waiting list. This could be taken as some measure of success, suggesting that more black and Hispanic patients have achieved access to transplantation centers and the transplantation waiting list. Optimistically, greater numbers of patients on the waiting list should directly translate into greater numbers of live donor kidney transplantations. It is possible, however, that the increase in the numbers of patients on the waiting list represents greater access to the waiting list for black or Hispanic patients of lower socioeconomic status who are typically less likely to identify a suitable living donor. Substantial evidence has documented lower rates of knowledge regarding transplantation, referral, and access to the waiting list and, ultimately, lower rates of transplantation for both black and Hispanic patients. Similarly, an association between socioeconomic status and referral and access to transplantation has been repeatedly identified. The response to concerns about disparities in access have included local and national initiatives, including the Medicare Improvements for Patients and Provider Act in 2008, which aimed to improve transplantation-related education within dialysis centers and referrals to transplantation centers by establishing links to reimbursement. Differences in socioeconomic status are important to consider because it also has been repeatedly documented that patients with low socioeconomic status, regardless of race/ethnicity, historically have been less likely to identify a suitable living donor. According to the data reported by Purnell et al,1 when comparing 1995-1999 with 2005-2009, the crude numbers of deceased donor kidney transplantation increased for black patients (from 5540 to 6402) and Hispanic patients (from 2294 to 3083) as shown in Table 3 in the article. Since that time, there was a further slight increase in the numbers of deceased donor kidney transplantation from 2005-2009 to 2010-2014 among Hispanic patients (from 3083 to 3214) and a slight decrease among black patients (from 6402 to 6130). However, the rates of deceased donor kidney transplantation were proportionally lower for all race/ethnicities when accounting for the increased numbers of patients appearing on the waiting list. Since 2014, the numbers of deceased donors nationally have increased (a trend unseen in the preceding decade) and correspond with the ongoing opioid epidemic. Based on United Network for Organ Sharing data as of November 24, 2017, the numbers of deceased donor kidney transplantation increased by 16% from 2014 to 2016. In these 2 years, the numbers of deceased donor kidney transplantation increased by 5% for whites, 23% for blacks, and 32% for Hispanics. In July 2017, the United Network for Organ Sharing announced a major “milestone” in the reduction of access disparities noting that the number of black and Hispanic Related article page 49 Opinion