Simultaneous pediatric kidney transplantation and ureterocystoplasty in a 20-month-old boy.

Kidney transplantation (KT) in children with end-stage renal disease and an abnormal bladder poses a complex management challenge. Ureterocystoplasty (UC) has been previously reported in older children with non-compliant bladders, but the timing and technique of repair are controversial. This case reports the youngest patient, a 20-month-old boy to undergo successful single-stage UC and living-related KT. UC was performed because of a fibrotic, non-compliant bladder. A temporary vesicostomy was placed to provide adequate drainage in the presence of urethral stenosis. The patient developed a single episode of pyelonephritis within the first six months post-operatively, but there were no other urologic complications. At 13 months, the renal function is excellent with a mean glomerular filtration rate of 100 mL/min/1.73 m(2) and no clinical evidence of rejection. This case demonstrates that simultaneous UC and KT can be safely performed even in infants with non-compliant bladders and renal failure.

Successful living related kidney transplantation across an anti-donor HLA antibody.

In preconditioning highly sensitized kidney transplant candidates, renal allograft outcomes have been better when the serum titer for class I anti-HLA donor-specific antibody (DSA) is low in the recipient at the time of transplantation. However, the ideal level to which the titer should be lowered is still controversial. We report a primary living related kidney transplant in a 34-year-old highly sensitized woman (pretransplant panel-reactive antibody=70%) with end-stage renal disease secondary to chronic glomerulonephritis. We sought to desensitize by lowering the DSA titer specifically to 1:4 pretransplant. A standard complement-dependent cytotoxicity cross-match with her donor (sister) was repeatedly negative, although she was positive for class I antibody against her mismatched HLA antigen (A*2402) at a titer up to 1:16 by the single-antigen flowbead assay. The target DSA titer of 1:4 before transplant was achieved by 12 sessions of plasmapheresis (PP) over 7 weeks, plus two intravenous immune globulin infusions (IVIG) (500 mg/kg/infusion). The patient outcome was excellent. Neither IVIG nor PP was needed posttransplant. The serum creatinine ranged between 0.5 mg/dL and 1.2 mg/dL, and no rejection episode was documented at 28 weeks posttransplant. Therefore, we encourage the use of IVIG and PP to lower the DSA titer to at least 1:4 before kidney transplantation in highly sensitized patients. Large prospective trials are needed to establish a consensus for pretransplant risk assignment and to evaluate the need for desensitization.

Intrapyloric injection of botulinum toxin a for the treatment of persistent gastroparesis following successful pancreas transplantation.

Intrapyloric injection of botulinum toxin A (BoTx) successfully improved symptoms in idiopathic and diabetic gastroparesis (DGP) refractory to medical treatment. Therefore, we used it in three pancreas transplant patients done in our institution during the last 18 months. They had severe, persistent DGP despite successful pancreas transplantation. They received 100 units of BoTx during the first injection. The clinical effect became evident within 2 weeks after the treatment, and lasted for an average of 29 weeks (range 14-44 weeks). The patients' subjective evaluation showed improvement of their symptoms and quality of life following BoTx. Patients 2 and 3 had recurrent symptoms at 44 and 24 weeks, respectively, after the first injection; they required a second dose of 90 and 80 units, respectively. They are doing well at 3 months follow-up. Intrapyloric injection of BoTx is safe and efficient. It should be considered for treating residual DGP following successful pancreas transplantation.

Mycophenolate mofetil in pediatric renal transplantation: non-induction vs. induction with basiliximab.

North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reports have shown anti-T cell antibody, OKT3, to be deleterious in pediatric renal transplant recipients treated with mycophenolate mofetil (MMF). Unlike OKT3, basiliximab is a chimeric monoclonal antibody to the alpha subunit of the interleukin-2 receptor on activated T-lymphocytes. We sought to examine the outcome of MMF with or without basiliximab induction therapy in pediatric renal transplantation. Between January 1998, and June 2001, 49 pediatric renal transplants were performed at our center and 41 met the criteria for this study. We retrospectively analyzed the records of 25 patients who received MMF, Prednisone, CSA or TAC, alone (group I) and 16 patients who received MMF, CSA or TAC, and Prednisone in combination with basiliximab (group II). The two groups were similar with respect to recipient or donor age, gender, ethnicity, donor source (LD vs. CAD), cold ischemia time, and primary diagnosis. The basiliximab group had a shorter follow up period because of its more recent addition to our pediatric immunosuppression protocol, 12.9 +/- 5.9 months vs. 35.5 +/- 7.2 months for group I (p < 0.0001). At 6 months, the acute rejection rate was 16% (group I) compared with 25% (group II) (p = 0.689). The patient and graft survival at 6 and 12 months were 100% respectively for both groups. Basiliximab was well tolerated without significant adverse events. At 6 months, there was no significant difference between the groups in the incidence of urinary tract infection or cytomegalovirus infection. These data suggest that in the short-term, MMF with or without basiliximab induction therapy appears to yield excellent and statistically similar outcomes. However, further controlled studies are necessary to verify these findings as well as to define the role of basiliximab in MMF-treated pediatric renal transplant recipients.

Hand-assisted laparoscopic donor nephrectomy is safe and results in increased kidney donation.

The impact of hand-assisted laparoscopic donor nephrectomy on kidney allograft function, perioperative complications, and organ supply was evaluated by retrospective analysis of 41 hand-assisted laparoscopic donor nephrectomy patients and their recipients between January and October 2003. Serum creatinine at discharge, length of stay, estimated blood loss, operative time, and perioperative complications were analyzed. The mean values for laparoscopic donors and their recipients were 1.2 +/- 0.3 and 1.3 +/- 0.8 mg/dL for creatinine, 3.3 +/- 0.8 and 6.7 +/- 3 days for length of stay, and 110.4 +/- 76.9 and 111.6 +/- 56 mL for estimated blood loss, respectively. No major complications occurred in the laparoscopic donors. The number of living kidney donors increased by 94% compared to the mean of the previous 4 years following implementation of the laparoscopic program. Hand-assisted laparoscopic donor nephrectomy is safe, results in excellent allograft function, and significantly increases donation.

Use of basiliximab with mycophenolate mofetil in kidney transplantation.

INTRODUCTION: Randomized, placebo-controlled studies have determined that administration of basiliximab (chimeric IL-2 receptor antagonist) decreases the acute rejection rate in kidney transplantation when used in combination with cyclosporine, azathioprine, and steroids. We report our experience using basiliximab with mycophenolate mofetil, a calcineurin inhibitor, and steroids in kidney transplantation. METHODS: We retrospectively analyzed 127 patients who received their first kidney transplant between September 1, 1998, and December 30, 2000, including 59 who received basiliximab (22 living and 37 cadaveric donor recipients) and the 68 that did not receive this antibody (31 living and 37 cadaveric donor recipients). The groups were demographically comparable for risk factors such as race, peak of panel-reactive antibody, delayed graft function, donor age, and cold ischemia time. The analysis assessed serum creatinine levels, acute rejection, cytomegalovirus infection, and posttransplant lymphoproliferative disease incidence as well as patient and graft survival at 6 months. RESULTS: Serum creatinine levels were 3 +/- 3.1 and 2.6 +/- 2.5 mg/dL (P =.346) at discharge, 1.5 +/- 0.6 and 1.7 +/- 1.1 mg/dL (P =.098) at 1 month, and 1.5 +/- 0.7 and 1.6 +/- 0.7 mg/dL (P =.454) at 6 months posttransplantation for patients treated with versus without basiliximab, respectively. Only one episode of acute rejection was seen among patients treated with basiliximab within 1 month posttransplantation versus three episodes among patients treated without basiliximab (P =.382). Three patients (5.1%) treated with basiliximab and two patients (2.9%) treated without basiliximab developed acute rejection within 6 months posttransplantation (P =.536). Patient and graft survivals at 6 months posttransplantation were not significantly different between patients treated with versus without basiliximab (100% and 100% versus 100% and 98.3%, respectively). There was no increased incidence of cytomegalovirus infection with the use of basiliximab (5.1% vs 5.9%, P =.844). There was only one case of posttransplant lymphoproliferative disease within 6 months posttransplantation in a patient treated without basiliximab. CONCLUSION: These data suggest that the routine addition of basiliximab to a mycophenolate mofetil-based regimens does not appear to be warranted. A larger prospective randomized study with longer follow-up is needed to confirm these results.

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation.

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation.

Small-diameter portacaval H-graft shunt: a paradigm shift back to surgical shunting in the management of variceal bleeding in patients with preserved liver function.

Small-diameter portacaval H-graft (SDPHG) shunts are partial portosystemic shunts that control variceal bleeding while preserving nutrient blood flow to the liver, minimizing postoperative encephalopathy and liver failure. Since July 1, 1997, we placed SDPHG shunts in 18 patients (age, 52.1 +/- 2.6 years; range, 35 to 72 years) with cirrhosis (Child's class A, B, and C in 6, 10, and 2 patients, respectively) and refractory variceal bleeding who were not candidates for transplantation. Ten procedures (55.6%) were urgent or emergent. SDPHG shunts effectively reduced the portacaval pressure gradient (18 +/- 3 v 5 +/- 2 mm Hg; P <.05). Surgical times (210 +/- 11 minutes), estimated blood losses (358.3 +/- 107.8 mL), transfusion requirements (0 transfusions in 10 patients; 55.6%; mean, 0.9 +/- 0.3 units), and postoperative hospitalization (7.7 +/- 1.0 days) were excellent. Surgical mortality (30 days) was 0%. During 14. 0 +/- 1.9 months (range, 1.1 to 29.1 months) of follow-up, 4 patients (22.2%) died, including both patients with Child's class C cirrhosis. The cumulative 1-year survival rate was 82.1% (Child's class A, B, and C, 83.3%, 90%, and 0%, respectively). Long-term survivors had significantly lower preoperative Child-Pugh scores compared with nonsurvivors (7.8 +/- 0.3 v 9.5 +/- 1.0; P <.05). Postoperative encephalopathy developed in 3 survivors (20%). Fifteen patients (83.3%) have not experienced rebleeding; shunt failure led to rebleeding in only 1 patient (5.6%). SDPHG shunt placement can be performed with low morbidity and surgical mortality. Nontransplantation candidates with Child's class A and B cirrhosis have excellent long-term survival with this safe, effective, and definitive treatment for refractory variceal bleeding.

Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus.

In recent years, tacrolimus (FK506, TAC) has been increasingly utilized in liver transplantation. However, long-term risks and benefits as compared with conventional cyclosporin A (CsA) have not been fully elucidated. This retrospective study examined the potential outcome differences between TAC- and CsA-based immunosuppressive therapy in pediatric liver transplant recipients. From March 1988 to December 1996, 218 children (aged 0.1-17 yr) underwent 238 orthotopic liver transplantations; 58.7% (128/218) were under 2 yr of age at time of transplant. Initially, the maintenance immunosuppressive regimen consisted of CsA and prednisone, with antilymphocytic preparations (MALG, ATGAM, and OKT3) as induction therapy. Subsequently, TAC was used first as rescue therapy for steroid refractory rejection in CsA patients and then as maintenance immunosuppression. Fifty-seven out of the 147 CsA patients were converted to TAC for various reasons while 71 patients were placed on TAC as primary maintenance immunosuppression. 62.6 per cent (92/147) of liver recipients on CsA experienced at least one biopsy-proven acute rejection episode as compared to 50.7% (36/71) for TAC patients (p = 0.09); likewise, 34% (50/147) of CsA patients had more than one episode of rejection vs. 18.3% (13/71) for patients on TAC (p < 0.02). Rejection was the reason for conversion from CsA to TAC in 29 of 57 patients. Conversely, 19.0% (28/147) of CsA patients had to be switched to TAC for reasons not related to rejection (i.e. side-effects). The overall incidence of histologically proven chronic rejection was 7.8% (17/218). 10.9 per cent (16/147) of the children who were on CsA initially developed chronic rejection, which was significantly higher compared with one of 71 TAC recipients (p < 0.02). Of these 16 CsA patients with chronic rejection, 50.0% (8/16) underwent retransplantation for graft failure (mean interval from time of diagnosis of chronic rejection to re-transplant, 4.0 months; range 1-8 months), whereas the TAC patient has remained clinically stable with normal liver function tests after 23 months of follow-up. One year after liver transplantation, 72.8% (107/147) of CsA patients were still on steroids (mean dosage 0.20 mg/kg/d), as compared to 42.3% (30/71) of the TAC patients (mean dosage 0.14 mg/kg/d). The incidence of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-infected patients was 2.2% (2/90), 7.0% (5/71) and 12.3% (7/57) for CsA, primary and TAC-converted groups, respectively. The overall incidence of PTLD was 6.9% (15/218). In summary, pediatric liver transplant recipients treated with TAC as primary maintenance immunosuppressive medication experienced significantly fewer episodes of rejection; especially chronic rejection, which lead to graft loss. However, the trade-off is a potential increased incidence of EBV-related PTLD in these patients.

Posttransplant lymphoproliferative disorders and gastrointestinal manifestations of Epstein-Barr virus infection in children following liver transplantation.

BACKGROUND: Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS: This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS: After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION: In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.

Allograft rejection after liver transplantation for autoimmune liver diseases.

Autoimmune liver diseases (AILD) may progress to liver failure, requiring liver transplantation as definitive therapy, and these immune-mediated disorders may predispose the patient to more frequent graft rejection. The objective of this study was to determine the effect of preexisting AILD on the incidence of allograft rejection after liver transplantation. Sixty-three patients who underwent liver transplantation between March 1988 and December 1994 for AILDs that included autoimmune hepatitis (AIH; n = 33) and primary biliary cirrhosis (PBC; n = 30) were retrospectively compared with 47 patients who underwent liver transplantation for alcoholic cirrhosis during the same time period. There was a lower incidence of acute allograft rejection in patients with AILD who received tacrolimus-based compared with cyclosporine-based immunosuppression (50% v 85.5%; P = .02). However, patients with AILDs overall had a higher incidence of acute rejection than patients with alcoholic cirrhosis (81% v 46.8%; P < .001), regardless of the type of immunosuppression. In addition, steroid-resistant rejection occurred more frequently in patients with AILDs than in patients with alcoholic cirrhosis (38.1% v 12.8%; P = .003). There was also a trend toward a higher incidence of chronic rejection in patients with AILDs compared with patients with alcoholic cirrhosis (11.1% v 2.1%), but this difference did not reach statistical significance. Patient and graft survivals at 1 and 3 years were similar between patients with AILDs and alcoholic liver disease. Compared with alcoholic cirrhosis, preexisting AILDs are associated with a higher incidence of acute allograft rejection and a trend toward more frequent chronic rejection.

Current status of living-related liver transplantation.

Living-related liver transplantation has come of age. This manuscript addresses the most important facets of the living-related liver transplant procedure including selection of the donor, the recipient operation, immunosuppression and rejection as well as the most common surgical complications. It also describes the results in terms of patient and graft survival, retransplantation and quality of life. Although living-related liver transplantation has not solved the problem of organ shortage, it has provided many children with an opportunity to live and enjoy life.

Orthotopic liver transplantation for hepatocellular carcinoma. Factors affecting long-term patient survival.

OBJECTIVE: To determine the influence of several clinicopathologic factors on the 3-year actuarial survival of patients with nonfibrolamellar hepatocellular carcinoma (HCC) following orthotopic liver transplantation (OLT). DESIGN: A case series of 26 consecutive patients with HCC treated with OLT, with a maximum follow-up of 90 months. SETTING: A tertiary care center. PATIENTS: Between March 1988 and December 1993, 521 OLTs were performed in 480 patients, 27 of whom had HCC. One patient was excluded because of donor-transmitted melanoma. Of the remaining 26 patients, there were 18 adults and 8 children, with a mean age of 41 years (range, 0.2-67.4 years). Fourteen patients (54%) had either hepatitis B (n = 6) or hepatitis C (n = 8), while 15 (58%) had coincidental tumor. INTERVENTION: OLT was performed using standard techniques. MAIN OUTCOME MEASURES: The effect of several clinicopathologic factors on 3-year actuarial patient survival. RESULTS: The overall actuarial survival rates for the 26 patients with HCC were 73%, 65.4%, and 65.4%, at 1, 2, and 3 years, respectively. Sixteen patients (62%) were alive at the time of this report, with 14 (54%) free of disease. None of the clinicopathologic factors significantly affected the 3-year patient survival rate. However, the rate of recurrent HCC was significantly higher in nonincidental vs coincidental tumors and in solitary vs multiple tumors. CONCLUSION: Our results suggest that HCC should not contraindicate OLT, as long-term patient survival and cure can be achieved. While patient selection is important, survival in patients with HCC after OLT is not always predictable using the usual clinicopathologic prognostic factors.

Sequential psychomotor skills development in laparoscopic colon surgery.

OBJECTIVES: To quantify the complexity of each of three skills used in laparoscopic colon surgery and to quantify the relative complexity of seven laparoscopic colon procedures on a graduated complexity scale. DESIGN: Five surgeons used a scale of 1 through 6 to measure the relative complexity of three laparoscopic skills (intracorporeal mobilization, intracorporeal devascularization, and intracorporeal anastomosis) to assess the relative difficulty of seven laparoscopic procedures (right colon resection, sigmoid colon resection, low anterior resection, Hartmann's procedure, left colon resection, abdominoperineal resection, and transverse colon resection) using detailed evaluation of their first 100 laparoscopic colon resections. SETTING: Three private community hospitals. MAIN OUTCOME MEASURES: The complexities of intracorporeal mobilization, intracorporeal devascularization, and intracoporeal anastomosis were recorded for seven laparoscopic colon procedures. RESULTS: The least complex procedure was right colon resection, followed in increasing complexity by sigmoid colon, Hartmann's procedure, low anterior resection, abdominoperineal resection, left colon resection, and transverse colon resection. The addition of each laparoscopic skill increased the complexity during each procedure. All three skills were not required for every procedure. CONCLUSIONS: Since all procedures do not require all three skills, skills can be learned sequentially if patients are chosen judiciously. A sequence of laparoscopic procedures performed by surgeons is recommended. The relative complexities for each procedure suggest an outline (map) for surgeons to use during laparoscopic colon surgery.