Surendra Shenoy

Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation.

Purpose:To evaluate outcomes of downstaging patients with advanced (American liver tumor study group stage III/IV) hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) to allow eligibility for orthotopic liver transplant (OLT). Methods:From 1999 to 2006, 202 patients with HCC were referred for transplant evaluation. Seventy-six (37.6%) patients with stage III/IV HCC were potential transplant candidates if downstaging was achieved by TACE. OLT was considered based on follow-up imaging findings. The number of patients who were successfully downstaged within the Milan criteria, tumor response using Response Evaluation Criteria in Solid Tumors criteria, findings at explant, and outcomes after transplant were tracked. Results:Eighteen of 76 (23.7%) patients had adequate downstaging to qualify for OLT under the Milan criteria. By Response Evaluation Criteria in Solid Tumors, 27/76 (35.5%) patients had a partial response, 22/76 (29%) had stable disease, and 27/76 (35.5%) had progressive disease. Seventeen of 76 (22.4%) patients who met other qualifications underwent OLT after successful downstaging (13/38 stage III;4/38 stage IV). Explant review demonstrated 28 identifiable tumors in which post-TACE necrosis was greater than 90% in 21 (75%). At a median of 19.6 months (range 3.6–104.7), 16/17 (94.1%) patients who underwent OLT are alive. One patient expired 11 months after OLT secondary to medical comorbidities. One of 17 (6%) OLT patients had recurrent HCC. This patient underwent resection of a pulmonary metastasis and is alive, 63.6 months from OLT. Conclusion:Selected patients with stage III/IV HCC can be downstaged to Milan criteria with TACE. Importantly, patients who are successfully downstaged and transplanted have excellent midterm disease-free and overall survival, similar to stage II HCC.

Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients.

BACKGROUND Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.

Short course induction immunosuppression with thymoglobulin for renal transplant recipients

BACKGROUND The aim of this study was to demonstrate that 3-days of induction immunosuppression with thymoglobulin was as effective and safe as a 7-day course and reduced initial hospitalization after transplantation. METHODS This was a prospective, nonrandomized trial of 40 consecutive patients receiving thymoglobulin induction for 3 days and followed for 1 year. An historical group of 48 patients that received 7 days of thymoglobulin served as controls. RESULTS At 1 year, acute rejection (5 vs. 4%), graft survival (95 vs. 98%) and patient survival were similar; a composite end point of freedom from death, rejection, or graft loss, the event-free graft survival, was similar as was the safety profile. In the 3-day group, lymphocyte depletion was more sustained and initial hospitalization was significantly shorter (6 vs. 8 days). CONCLUSION Three-day induction with thymoglobulin is as effective and safe as seven days, decreases initial hospitalization and causes more sustained lymphocyte depletion.

Peripheral blood microchimerism in human liver and renal transplant recipients : Rejection despite donor-specific chimerism

BACKGROUND Development of donor-specific microchimerism (DSM) has been proposed as one of the possible mechanisms for induction and maintenance of allograft tolerance. The aim of this study was to determine: (1) the state of DSM in liver transplant (LTx) and renal transplant (RTx) recipients, (2) whether the persistent presence of an allograft is a requirement for maintenance of chimerism, and (3) whether donor-specific blood transfusions (DST) facilitate chimerism development in RTx recipients and whether this correlates with allograft function. METHODS Qualitative and quantitative analysis of DSM in peripheral blood of LTx and RTx recipients was assessed by polymerase chain reaction and competitive polymerase chain reaction using HLA-DR probes for mismatched antigens between the donor and recipient. RESULTS LTx recipients (11 of 12) who had or were having rejection were positive for DSM in circulation compared with 4 of 11 with normal allograft function (P<0.01). The number of donor cells did not correlate with allograft function. LTx recipients (4 of 4) who lost their first allograft and underwent retransplantation retained DSM for the first donors. RTx recipients who received DST (8 of 8) were positive for DSM compared with 6 of 12 of nontransfused recipients (P<0.045). CONCLUSIONS The results suggest that LTx and RTx recipients undergo rejection despite DSM. The development of DSM may not be a prerequisite for normal allograft function. Once DSM is established, the presence of the allograft is not required for maintenance of chimerism. DST facilitated the development of DSM in RTx recipients. Direct correlation was not observed between the development of DSM and allograft function in either DST or nontransfused RTx recipients.

Advanced Donor Age Alone Does Not Affect Patient or Graft Survival after Liver Transplantation

BACKGROUND Individuals greater than 60 years old donate an important portion of the organs available for orthotopic liver transplantation (OLT), but use of donors in this age group remains controversial. We hypothesized that proper selection of donors older than age 60 would not disadvantage recipients in terms of patient and graft survival. STUDY DESIGN All OLTs performed at our center between January 1, 1990, and July 31, 2007, were divided into groups based on donor age: donors 60 years old or more and donors less than 60 years old. Recipients in each group were compared based on graft and patient survival at 1, 3, and 5 years, Model for End-Stage Liver Disease (MELD) scores, cold ischemic times, and era of transplant (before or after 2001). RESULTS There were 741 recipients who met inclusion criteria. Ninety-one patients received livers from donors 60 years old or older, and 650 patients had donors younger than 60 years old. Overall patient survival rates in the group using donors 60 or older were 86.8%, 72.6%, and 67.6% at 1, 3, and 5 years, respectively, and did not differ significantly from survival in the group receiving transplants from donors less than 60 (87.1%, 81.8%, and 75.5%; p=0.39). The 1-, 3-, and 5-year graft survivals in patients receiving transplants from donors 60 or older were 82.4%, 65%, and 62.5%, respectively, and were not significantly different from those in the group using donors younger than 60 (84%, 78.6%, and 72.3%, respectively; p=0.39). Neither patient survival nor graft survival in recipients of organs from donors 60 or older was affected by Model of End-Stage Liver Disease score. Recipients of older-donor livers had improved outcomes after 2001, which correlated with significant improvements in cold ischemic times. CONCLUSIONS Our data suggest that age alone does not adversely affect recipient outcomes. When properly selected, donors older than 60 represent an important and safe increase in the liver donor pool.

Living-unrelated renal transplantation provides comparable results to living-related renal transplantation: A 12-year single-center experience

BACKGROUND The increasing success of renal transplantation is paralleled by the increased size of the waiting list. Efforts to increase the donor pool have included the use of living-unrelated kidney donors (LURDs). METHODS During a 12-year period our center performed 309 transplantation from living donors; 279 patients received living-related donor (LRD) transplants, and 30 patients received LURD transplants. During the same period 543 patients received cadaveric renal donor transplants. A total of 86.7% of LURD transplants were spousal transplants. A total of 29% of the patients who received LRDs were human leukocyte antigen-identical with their donors and 53% were haploidentical, versus 0 human leukocyte antigen-identical or haploidentical in the LURD group. RESULTS Twenty-seven (90%) Of 30 LURD recipients are alive, as are 240 (86%) of 279 LRD recipients. Mean current creatinine is 1.6 mg/dl for the LURD group and 1.7 mg/dl for the LRD group Kaplan-Meier 1- and 5-year graft survival was 94.9% and 82.9% for the LRD group, 93.1% and 85.9% for the LURD group (p = not significant), and 84.6% and 70.7% for the cadaveric renal donor group (p < 0.05). CONCLUSIONS LURD patient and graft survival is comparable to LRD transplants despite inferior human leukocyte antigen matching. LURD transplant survival is superior to that of cadaveric renal donor transplants. LURDs are an excellent but underused source of organs for renal transplant recipients.

Sirolimus conversion in liver transplant recipients with renal dysfunction: A prospective, randomized, single-center trial

This pilot trial was designed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction. Forty patients with renal dysfunction (24-hr CrCl 40–80 mL/min) were randomized to be withdrawn from the calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control, P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection. Side effects of SRL were limited and included hyperlipidemia requiring treatment (15%), pruritis (5%), and mouth sores (25%). In this trial, SRL-based immunosuppression was a safe alternative to CNI. Although early improvements were observed, withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up.

Serological evidence of past hepatitis B infection in liver donor and hepatitis B infection in liver allograft

The presence of hepatitis B surface and core antibodies (anti-HBs and anti-HBc) in a liver donor without hepatitis B surface antigen is taken to indicate resolution of hepatitis B and is not considered to contraindicate donation. We report a liver transplant recipient who developed hepatitis B after such a donation. It seems that hepatitis B virus can reside in the liver of a patient who has seemingly recovered from his disease. We recommend avoidance of liver transplants from donors who are positive for anti-HBs and anti-HBc.

Prospective, Pilot, Open-Label, Short-Term Study of Conversion to Leflunomide Reverses Chronic Renal Allograft Dysfunction

Leflunomide (LEF) is a synthetic isoxazole derivative with anti‐inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. We performed a pilot, crossover trial in 22 renal transplant recipients who were converted from azathioprine (AZA) or mycophenolate mofetil (MMF) to LEF in an effort to slow progression of renal dysfunction [deteriorating renal function (n = 5), cyclosporine (CyA) nephrotoxicity (n = 4) or biopsy‐proven CAN (n = 13)]. Baseline maintenance immunosuppression consisted of CyA, AZA or MMF and prednisone. Six‐month postconversion patient and graft survival was 100% and 91%, respectively. Mean serum creatinine 6 months preconversion was 2.2 ± 0.6 mg/dL, at initiation was 3.0 ± 1.1 mg/dL, and 6 months postconversion was 2.8 ± 1.3 mg/dL. The rate of change in serum creatinine was 35 ± 39%/6 months preconversion and − 5 ± 21%/6 months postconversion to LEF (p = 0.003). Two patients discontinued LEF for diarrhea and myalgia. No readmissions, increase in liver function tests, infections or acute rejection episodes occurred. Mean CyA levels did not change, 146 ± 72 ng/mL pre‐LEF vs. 132 ± 51 ng/mL post‐LEF, p = NS. Conversion to LEF reversed progression of chronic renal allograft dysfunction with minimal toxicity.

A novel technique of vascular anastomosis to prevent juxta-anastomotic stenosis following arteriovenous fistula creation

OBJECTIVES Juxta-anastomotic stenosis (JAS) is one of the predominant causes of arteriovenous fistula (AVF) failure, with the reported incidence as high as 65%. We hypothesized that technical modification to alter the outflow vein configuration using the novel piggyback Straight Line Onlay Technique (pSLOT) would prevent JAS and improve AVF maturation. METHODS Intention-to-treat analysis of the outcomes of consecutive distal radiocephalic (RC) fistulas performed by a single operator with three different anastomotic techniques using a prospectively maintained database. Traditional end-to-side technique (ETS), side-to-side straight-line onlay technique (SLOT, STS) and pSLOT in RC AVF created in 125 consecutive patients between 1/2004 and 12/2007 were compared. AVF maturation was evaluated by ultrasonography at 4 to 6 weeks and use for dialysis. RESULTS The mean age of the study group was 53.1 ± 20.7 years, the male-to-female ratio was 61:64, and the races studied were African American (66; 52.8%) and Caucasian (54; 43.2%). The primary disease for renal failure was hypertension (54; 43.2%) and diabetes (51; 40.8%). Brachial artery flow at maturation was 1103 ± 531 mL/min. Incidence of early JAS was 9.8% and late 14.6%. The clinico-demographic variables between ETS (n = 57), STS (n = 12), and pSLOT (n = 54) were similar. The median follow-up between three groups: ETS (19 months), STS (12 months), and pSLOT (19 months; P = .1), was similar. There was a significant decrease in JAS development in pSLOT patients (P = .04). pSLOT patients also revealed decreased overall fistula failure (ETS 40.3%, STS 33.3%, pSLOT 16.7%; P = .01). CONCLUSIONS There was significant reduction in JAS and improvement in AVF maturation with pSLOT. This study provides evidence highlighting the role of outflow vein configuration in AVF maturation. Minimal alteration of vein wall configuration and avoidance torsion using pSLOT technique improves AVF maturation.