CD4 Count in HIV- Brain-Dead Donors: Insight into Donor Risk Assessment for HIV+ Donors.

BACKGROUND: The Human Immunodeficiency Virus (HIV) Organ Policy Equity Act allows for transplantation of organs from HIV-infected individuals (HIV+), provided it is performed under a research protocol. The safety assessment of an organ for transplantation is an essential element of the donation process. The risk for HIV-associated opportunistic infections increases as circulating CD4+ lymphocytes decrease to less than 200 cells/µL; however, the numbers of circulating CD4+ cells in the HIV-negative (HIV-) brain-dead donor (BDD) is not known. METHODS: Circulating T-lymphocyte subset profiles in conventional HIV- BDD were measured in 20 BDD in a clinical laboratory. RESULTS: The mean age of the BDD cohort was 48.7 years, 95% were white and 45% were women. The average body mass index was 29.2 kg/m. Cerebrovascular accident (40%) was the most prevalent cause of death. Sixteen (80%) subjects had a CD4 count ≤441 cells/µL (lower limit of normal) and 11 (55%) had a CD4 count less than 200 cells/µL; 11 (55%) subjects had a CD8 count ≤125 cells/µL (lower limit of normal). CD4/CD8 ratio was below normal in 3 patients (normal, 1.4-2.6). No recipient had a recognized donor-associated adverse event. CONCLUSIONS: Absolute numbers of CD4 and CD8 T-lymphocytes are commonly reduced after brain death in HIV- individuals. Thus, CD4 absolute numbers are an inconsistent metric for assessing organ donor risk, irrespective of HIV status.

Evolution of Living Donor Nephrectomy at a Single Center: Long-term Outcomes With 4 Different Techniques in Greater Than 4000 Donors Over 50 Years.

BACKGROUND: The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes. METHODS: All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques. RESULTS: We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P < 0.001) and heavier (P < 0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P < 0.001). All 3 LDN modalities required a longer operative time (P < 0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P < 0.001) and reduced the incidence of intraoperative complications (P < 0.001) and hospital length of stay (P < 0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (<30 day, P < 0.001) and long-term (>30 day, P < 0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P < 0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]). CONCLUSIONS: In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.

Longterm health-related quality of life after living liver donation.

There are little data on longterm outcomes, health-related quality of life (HRQoL), and issues related to living donor right hepatectomy specifically. We studied longterm HRQoL in 127 living liver donors. A donor-specific survey (DSS) was used to evaluate the living liver donor morbidity, and the 36-item short-form health survey (short-form 36 health survey, version 1 [SF-36]) was used to assess generic outcomes. The DSS was completed by 107 (84.3%) donors and the SF-36 by 62 (49%) donors. Median follow-up was 6.9 years. Of the 107 donors, 12 (11.2%) donors reported their health as better, whereas 84 (78.5%) reported their health the same as before donation. Ninety-seven (90.7%) are currently employed. The most common postdonation symptom was incisional discomfort (34%). Twenty-four donors (22.4%) self-reported depression symptoms after donation. Ninety-eight (91.6%) rated their satisfaction with the donation process ≥ 8 (scale of 1-10). Three factors-increased vitality (correlation, 0.44), decreased pain (correlation, 0.34), and a recipient who was living (correlation, 0.44)-were independently related to satisfaction with the donor experience. Vitality showed the strongest association with satisfaction with the donor experience. Mental and physical component summary scale scores for donors were statistically higher compared to the US population norm (P < 0.001). Donors reported a high satisfaction rate with the donation process, and almost all donors (n = 104, 97.2%) would donate again independent of experiencing complications. Our study suggests that over a longterm period, liver donors continue to have above average HRQoL compared to the general population.

Ten-year outcome after rapid discontinuation of prednisone in adult primary kidney transplantation.

BACKGROUND AND OBJECTIVES: Rapid discontinuation of prednisone after kidney transplantation potentially allows for minimization of steroid-related side effects. Although intermediate-term data with rapid discontinuation of prednisone have been promising, concern still exists regarding long-term outcomes. The 10-year experience is reported herein. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between October 1, 1999 and December 31, 2010, 1241 adult primary kidney transplants (791 living donor and 450 deceased donor) were performed using a protocol in which prednisone is discontinued after postoperative day 5. The 10-year actuarial recipient and graft survival rates and prednisone-related side effects were studied. RESULTS: Ten-year actuarial patient survival was 71% for living donor transplants and 62% for deceased donor transplants; 10-year graft survival was 61% for living donor transplants and 51% for deceased donor transplants, and was comparable to 10-year Scientific Registry of Transplant Recipients national data. Ten-year death-censored graft survival was 79% for living donor transplants and 80% for deceased donor transplants. Ten-year acute rejection rates were 25% for deceased donor transplants and 31% for living donor transplants; 10-year chronic rejection (interstitial fibrosis/tubular atrophy) rates were 39% for deceased donor transplants and 47% for living donor transplants. For nondiabetic recipients of living donor or deceased donor allografts, the incidence of new-onset diabetes was significantly lower than in historical controls on prednisone (P<0.001). We also found significantly reduced rates of cataracts, avascular necrosis, and cytomegalovirus infection in some subgroups. CONCLUSIONS: Prednisone-related side effects can be minimized in a protocol incorporating rapid discontinuation of prednisone for maintenance immunosuppression. Ten-year patient and graft outcomes remain acceptable.

Long-term outcome in 42 pediatric liver transplant patients with alpha 1-antitrypsin deficiency: a single-center experience.

INTRODUCTION: We examined the long-term outcome of transplantation for alpha 1-antitrypsin deficiency (A1ATD). METHOD: Data were reviewed on 42 transplants in 35 children with A1ATD over 42 yr and compared with 129 transplants in 116 children with biliary atresia (BA). RESULTS: Over 50% of patients were followed up for >10 yr. A1ATD were older than BA at transplantation, median age, 6.0 vs. 1.0 yr (p < 0.0001), and transplanted earlier in the course of liver failure (total bilirubin, 2.7 mg/dL [1.4-6.9] vs. 9.7 mg/dL [2.9-15.4], p = 0.005). Patient survival was greater in A1ATD than BA: one-yr post-transplant, 82.7% vs. 67.9%; five yr, 76.5% vs. 60.2%; and 10 yr, 76.5% vs. 55.9% (p = 0.03). Death-censored graft survival was similar: one-yr post-transplant, 68.4% vs. 66.2%; five yr, 68.4% vs. 55.8%; and 10 yr, 68.4% vs. 52.5% (p = 0.2). Deaths were from infection, hemorrhage, and graft failure <6 months post-transplant. Patient survival improved at five yr from 33.3% pre-cyclosporine (CSA) (1969-1984) (n = 6) to 76.5% in the CSA era (1985-1994) (n = 17) and 100% with tacrolimus (1995-2006) (n = 12) (p = 0.007). CONCLUSIONS: The age at transplantation and the degree of liver dysfunction were related to the differences in graft and patient survival between A1AT and BA.

Transdiaphragmatic adrenalectomy for metastatic cervical adenocarcinoma: a technical case report.

We present a 60-year old woman with recurrent cervical adenocarcinoma who presented with metastasis to both lungs and to her right adrenal gland. A thoracotomy was performed for resection of her pulmonary metastasis and then the right adrenal gland was excised through a trans-diaphragmatic approach. The adrenal gland resection was more complex due to involvement of the tumor with the inferior vena cava (IVC) which was repaired with a PTFE patch graft. This case demonstrates both an interesting approach to surgical resection of multiple metastases as well as a safe, although more challenging, alternative to partially resect and repair the IVC.

Angioimmunoblastic T-cell lymphoma in bone marrow: a morphologic and immunophenotypic study.

Angioimmunoblastic T-cell lymphoma is known to frequently involve bone marrow. However, the histologic and immunophenotypic features of angioimmunoblastic T-cell lymphoma at this site are poorly defined. We assessed 27 bone marrow specimens involved by angioimmunoblastic T-cell lymphoma from 20 patients. Histologically, bone marrow involvement was predominantly multifocal (74%) and exhibited a nodular pattern (78%), often associated with other patterns. Using immunohistochemistry, programed death-1 and CD10 were expressed by atypical lymphocytes in 17 (85%) of 20 and 5 (18.5%) of 27 specimens, respectively. CXCL13 was not expressed by atypical lymphocytes in all cases but did stain stromal cells consistent with follicular dendritic cells in 1 case. BCL-6 as a single antibody was difficult to interpret because many normal bone marrow cells are dimly positive, but BCL-6/CD3 dual staining highlighted BCL-6+ T-cells in all cases assessed. Antibodies specific for CD21 and CD35 did not highlight follicular dendritic cells in any biopsy specimens. Flow cytometry immunophenotyping revealed a CD3+CD10+ T-cell population in 2 (25%) of 8 cases assessed. We conclude that the recognition and classification of angioimmunoblastic T-cell lymphoma in bone marrow are made difficult by the uncommon expression of CD10 (25%), rarity of follicular dendritic cells, and lack of CXCL13 expression at this site. This is most likely attributable to the very different microenvironment of the bone marrow relative to lymph nodes and, in particular, the absence of follicles in bone marrow. By contrast, programed death-1 immunohistochemical staining and double labeling using antibodies specific for BCL-6 and CD3 were helpful in appreciating the follicular T-helper cell immunophenotype of angioimmunoblastic T-cell lymphoma.

Graft weight/recipient weight ratio: how well does it predict outcome after partial liver transplants?

Partial graft liver recipients with graft weight/recipient weight (GW/RW) ratios < 0.8% are thought to have a higher incidence of postoperative complications, including small-for-size syndrome (SFSS). We analyzed a cohort of such recipients and compared those with GW/RW < 0.8% to those with GW/RW >or= 0.8%. Between 1999 and 2008, 107 adult patients underwent partial graft liver transplants: 76 from live donors [living donor liver transplantation (LDLT)] and 31 from deceased donors [split liver transplantation (SLT)]. Of these, 22 had GW/RW < 0.8% (12 with LDLT and 10 with SLT), and 85 had GW/RW >or= 0.8% (64 with LDLT and 21 with SLT). The baseline demographics and median length of follow-up were similar. SFSS developed in 3 recipients with GW/RW < 0.8% (13.6%) and in 8 recipients with GW/RW >or= 0.8% (9.4%; P = not significant). Other early complications were similar between the 2 groups. Inflow modification with splenic artery occlusion was performed in 13 recipients: 7 with GW/RW < 0.8% and 6 with GW/RW >or= 0.8%. Graft survival at 1 year post-transplant did not differ (91% versus 92%; P = not significant). In conclusion, GW/RW did not appear to be the only determinant of outcome after partial liver transplantation. Using techniques such as inflow modification may help to prevent some of the problems seen with smaller grafts.

Kidney transplant half-life (t[1/2]) after rapid discontinuation of prednisone.

Protocols incorporating rapid discontinuation of prednisone (RDP) after kidney transplantation have been associated with good short-term results. However, concern remains that RDP will be associated with decreased long-term graft survival rates. We compared kidney transplant half-life (t1/2) for recipients treated with antibody induction, calcineurin inhibitor, antimetabolite, and RDP versus historical controls treated with antibody induction, calcineurin inhibitor, antimetabolite, and maintenance prednisone. For both living and deceased donor recipients, we found no difference between groups. We also found no differences in rate of graft loss to acute rejection or to tubular atrophy and interstitial fibrosis. Our study suggests that long-term graft outcome is not decreased when using RDP protocols versus chronic maintenance prednisone.

Delayed splenic artery occlusion for treatment of established small-for-size syndrome after partial liver transplantation.

We looked at the impact of delayed splenic artery occlusion (SAO) on recipients with established small-for-size syndrome (SFSS) after partial graft liver transplantation [either from a living donor (LD) or split from a deceased donor (DD)]. Between 1999 and 2007 we performed a total of 100 partial liver transplantations in adult recipients: 66 LD transplantations and 34 DD split transplantations. Of these, 7 (7%) developed SFSS, diagnosed by the clinical features of cholestasis, coagulopathy, and ascites. Mean graft weight/recipient weight (GW/RW) ratio in these 7 recipients was 0.94%. Five of these 7 recipients underwent relaparotomy at a mean of 10 days post-transplantation to rule out a technical complication, and then intraoperative splenic artery ligation was performed. The other 2 recipients were treated radiologically by splenic artery coiling-at 9 and 13 days post-transplantation. Median serum bilirubin at the time of the splenic artery procedure was 20 mg/dL; by 3 weeks postprocedure this had decreased to 2.5 mg/dL. Of the 7 recipients with SFSS, 6 improved and eventually obtained normal graft function; 1 recipient did not improve and ultimately underwent retransplantation because of persistent cholestasis and failure to thrive. Delayed SAO represents a potential option for the treatment of recipients with established SFSS after partial liver transplantation.

Posttransplant diabetes mellitus and acute rejection: impact on kidney transplant outcome.

BACKGROUND: The benefits (e.g., low acute rejection [AR] rate) vs. the long-term risk of each immunosuppressive protocol may determine the protocol's value. METHODS: We studied the long-term impact of new-onset posttransplant diabetes (PTDM) and/or AR in 1,487 adult, primary transplant, nondiabetic recipients. Per Cox regression, donor source, AR, and PTDM were independent risk factors for graft loss (each, p<.0001). Recipients were subdivided by donor source and into these 4 groups: no AR, no PTDM [n=857]; no AR, PTDM [n=134]; > or =1 AR, no PTDM [n=403]; > or =1 AR, PTDM [n=93]. RESULTS: There was a significant difference between groups in 15-yr actuarial graft survival (GS) and death-censored (DC) GS (p<.0001). Importantly, > or =1 AR had more impact on 15-yr GS and DC GS than did PTDM; the worst outcome was for those having both AR and PTDM. In separate analyses, we censored those with >1 AR; and then only compared those developing AR or PTDM in the first year. The results were similar--the AR (no PTDM) group did worse than the PTDM (no AR) group (p<.001). CONCLUSIONS: Determining long-term risks associated with immunosuppressive protocols is important for treating future patients. Our data suggests that 15-year actuarial outcome (GS and DC GS) is worse for those developing AR than for those developing PTDM.

Steroid-free immunosuppression in kidney transplant recipients: the University of Minnesota experience.

As results after transplants continue to improve, the burden associated with long-term immunosuppression and the complications associated with these agents become more significant. Recent trends in immunosuppression minimization strategies show that prednisone minimization protocols are not associated with significantly increased acute rejection or chronic graft dysfunction. With long-term data now available, we can see that the majority of such recipients (>80%) can remain prednisone free. There seems to be no compromise in terms of long-term results, and a definite improvement with regard to steroid-related and viral complications. These protocols can be used in minorities, children, and higher immunologic risk kidney transplant recipients, and in liver and pancreas recipients. The question of what is the ideal maintenance agent to couple with prednisone-free regimes remains unclear, and it may be that different agents may be better suited for different groups of recipients. Why is prednisone minimization now possible, when previous attempts were unsuccessful? Several explanations are possible. Early attempts concentrated on steroid withdrawal - removing prednisone once the patient had been on therapy for at least 3 months (18-20). Outcomes differ between studies reporting rapid prednisone withdrawal and those reporting prednisone withdrawal at a later time, but it is not clear why rapid prednisone withdrawal has succeeded and late prednisone withdrawal has failed. Other factors may include the routine use of polyclonal antibody for induction therapy and the use of newer immunosuppression agents such as MMF, TAC, and SRL. Finally, the newer trials of prednisone minimization have been performed in a different era, a time when results have improved as has our understanding of the risk factors associated with long-term graft survival. While ongoing follow-up of this group of patients will continue to be important, our experience suggests that maintenance prednisone is likely not required for the majority of kidney transplant recipients today.

Risk factors for rising creatinine in renal allografts with 1 and 3 yr survival.

BACKGROUND: Determining factors associated with negative slope of inverse creatinine vs. time (1/Cr vs. t) may help prevent a decline in renal allograft function. METHODS: A total of 1389 adult recipients of primary renal transplants were divided into quartiles based on the slope of 1/Cr vs. t calculated from 6 and 12 months post transplant. A multivariate analysis of risk factors for being in the worst vs. best quartile employed these variables: donor source, HLA mismatch, recipient age, donor age, panel-reactive antibody (PRA), acute rejection (AR), 3-month cyclosporin A (CsA) level, 1-yr CsA level and acute tubular necrosis. Two separate analyses compared risk factors in patients with 1 and 3 yr survival, respectively. RESULTS: In recipients with > or = 1 yr graft survival, high PRA and AR were associated with negative slopes of 1/Cr vs. t. For those with > or = 3 yr graft survival, both AR and 3-month CsA level > 150 ng/mL were significant risk factors, using both 6- and 12-month slopes. Stratification of AR showed 1 AR episode > or = 6 months and multiple AR episodes carried significant risk for negative slopes. CONCLUSION: Optimization of allograft function invokes a conundrum between the needs to avoid both AR and high early CsA levels. We support a policy of carefully balancing these two risks.

Biliary cystadenomas: hormone receptor expression and clinical management.

Biliary cystadenomas with mesenchymal stroma are neoplasms whose growth may be hormone sensitive. This study profiled the immunohistochemistry of these lesions to clarify the pathophysiology and define clinical management. Twelve patients with biliary cystadenomas were identified. Tissue was tested with a panel of probes including estrogen and progesterone receptors and compared to pancreatic and ovarian cystadenomas. Epithelial ER, PR, CD117, or SMA expression was negative in all three tumors. Epithelial CD10 expression was seen in 60% biliary, 75% pancreatic, and 0% ovarian tumors. Biliary cystadenoma stromal expression was ER+ (70%), PR+ (60%), CD10+ (40%), and c-kit+ (0%). Symptoms were seen in 92% patients. Percutaneous sclerotherapy and incomplete resection were associated with recurrence. Enucleation was the least morbid surgical technique. A role for hormonally mediated growth of biliary cystadenomas occurring through the stroma, rather than the epithelium, is suggested. Management remains complete surgical resection.

Hepatitis B prophylaxis post-liver transplant without maintenance hepatitis B immunoglobulin therapy.

BACKGROUND: We examined outcomes in recipients who underwent a liver transplant for HBV-induced liver disease and received a protocol for prophylaxis that did not use HBIG maintenance. RESULTS: Between October 2002 and July 2005, a total of 14 liver transplant recipients were identified that met the study criteria. Mean recipient age was 47.6 yr; mean donor age was 37.2 yr. Category of transplant was as follows: cadaveric liver (n = 10, 71%), cadaveric split-liver (n = 2, 14%), and cadaveric liver-kidney (n = 2, 14%). Liver disease was diagnosed at a mean of 7.3 yr before transplant; three (21%) had a coexisting hepatocellular cancer at the time of transplant. Pre-transplant, all 14 (100%) recipients were hepatitis B surface antigen (HBsAg) positive, and 11 (79%) were HBV DNA positive (mean viral load of 251.2 pg/mL). Three (21%) were E antigen positive, and one (7%) was D antigen positive. Pre-transplant, seven patients (50%) were on anti-viral therapy and there was documented diminution in viral loads after initiating anti-viral therapy in 3 cases. Three (21%) were hepatitis C virus (HCV) antigen positive and all had low-RNA titers. With mean follow-up of 14.1 months, all 14 patients are alive with a functioning graft. Mean ALT, AST and total bilirubin values are currently at 43.2, 32.2, and 0.84, respectively. One recipient remains HBsAg surface antigen positive post-transplant but has normal lab values. The remaining recipients have no evidence of HBV recurrence by serology and protocol biopsies. The regimen has been well tolerated without the need for drug reduction or discontinuation because of side-effects. CONCLUSION: Longer follow-up is needed, but this regimen may represent an alternative to chronic HBIG maintenance therapy.

A prospective randomized trial of steroid-free maintenance regimens in kidney transplant recipients--an interim analysis.

We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.

A comparison of surgical outcomes and quality of life surveys in right lobe vs. left lateral segment liver donors.

Concern remains regarding the possibly higher risk to living liver donors of the right lobe (RL), as compared with the left lateral segment (LLS). We studied outcomes and responses to quality of life (QOL) surveys in the two groups. From 1997 to 2004, we performed 49 living donor liver transplants (LDLTs): 33 RL and 16 LLS. Notable differences included a higher proportion of female and unrelated donors in the RL group. A significantly larger liver mass was resected in RL (vs. LLS) donors: 720 (vs. 310) g, p = 0.01; RL donors also had greater blood loss (398 vs. 240 mL, p = 0.04) and operative times (7.2 vs. 5.7 h, p = 0.05). However, those findings did not translate into significant differences in donor morbidity. The complication rate was 12.5% in LLS donors and 9.1% in RL donors (p = ns). Per a QOL survey at 6 months postdonation, no significant differences were noted in SF-12 scores for the two groups. Recovery times were somewhat longer for RL donors. Mean time off work was 61.0 days for RL donors and 32.4 days for LLS donors (p = 0.004). RL donation is associated with greater operative stress for donors, but not necessarily with a more complicated recovery or differences in QOL.

Living donor and split-liver transplants in hepatitis C recipients: does liver regeneration increase the risk for recurrence?

Concern exists that partial liver transplants (either a living donor [LD] or deceased donor [DD] in hepatitis C virus (HCV)-positive recipients may be associated with an increased risk for recurrence. From 1999 to 2003, at our institution, 51 HCV-positive recipients underwent liver transplants: 32 whole-liver (WL) transplants, 12 LD transplants and 7 DD split transplants. Donor characteristics differed in that WL donors were older, and LD livers had lower ischemic times. Recipient characteristics were similar except that mean MELD scores in LD recipients were lower (p < 0.05). With a mean follow-up of 28.3 months, 46 (90%) recipients are alive: three died from HCV recurrent liver disease and two from tumor recurrence. Based on 1-year protocol biopsies, the incidence of histologic recurrence in the three groups is as follows: WL, 81%; LD, 50% and DD split, 86% (p = 0.06 for LD versus WL). The mean grade of inflammation on the biopsy specimens was: WL, 1.31; LD, 0.33 and DD split, 1.2 (p = 0.002 for LD versus WL; p = 0.03 for LD versus DD split). Mean stage of fibrosis was: WL, 0.96; LD, 0.22 and DD split, 0.60 (p = 0.07 for LD versus WL). Liver regeneration does not seem to affect hepatitis C recurrence as much, perhaps, as factors such as DD status, donor age and cold ischemic time.