Early intra-abdominal infections associated with orthotopic liver transplantation.

BACKGROUND: Postoperative infections remain a significant problem among liver transplant recipients (LTRs). An early cause of morbidity after liver transplantation is intra-abdominal infection (IAI) about which there are limited data. METHODS: We report a retrospective review of 169 adult LTRs from January 1, 2002 to June 9, 2006, comparing those who developed early postoperative IAI (peritonitis, biliary tract infection, abdominal abscess, or enteritis) with those who did not to identify clinical features and risk factors, analyze epidemiology, and assess graft and patient survival. RESULTS: Sixty-eight patients (40%) had 104 infections, with 148 pathogens isolated. Leukocytosis (53%) and fever (34%) were the most common clinical features, and peritonitis (43%) was the most common manifestation. Enterococcus spp., the most frequent single pathogens, comprised 26% of organisms cultured. There were significant associations of IAI with pretransplant ascites (P=0.002), posttransplant dialysis (P=0.015), and non-IAI surgical complications (P<0.001). There was a trend toward graft failure in patients with IAI (P=0.051) but increased mortality was not associated with IAI. Use of pretransplant antibiotics was significantly associated with development of multiple drug-resistant organisms in IAI (P=0.032). CONCLUSION: IAI occurred at a relatively high rate in the early postoperative period, and fever was not a major indicator. In patients receiving antibiotics within 2 weeks before transplantation, multiple drug-resistant organisms often caused IAI. In addition, the presence of pretransplant ascites, posttransplant dialysis, and wound infection or reoperation after transplant should alert one to the increased risk of IAI in LTRs.

Lessons learned in pediatric small bowel and liver transplantation from living-related donors.

BACKGROUND: Children are the primary candidates for intestinal transplant with more than 70% requiring a combined liver-bowel transplant. We report our single-center experience with living donor intestinal transplantation (LDITx) and combined living donor intestinal and liver transplant (CLDILTx) in pediatric patients. PATIENTS AND METHODS: Between October 2002 and June 2006, 13 living donor intestinal grafts were transplanted in 10 recipients. In five cases CLDILTx was performed. The intestinal grafts consisted of a 150-cm segment of ileum, whereas the liver transplant was completed using standard left lateral grafts. RESULTS: No complications occurred in any donors. In CLDILTx recipients, the patient survival at 1 and 2 years was 100%, the liver graft survival 100%, and the bowel graft survival 80%; the patient who lost the initial intestinal graft was successfully retransplanted. In LDITx recipients, the patient and graft survival at 1 and 3 years were 60% and 50%, respectively. Two isolated LDITx recipients, both 6 months of age and low body weight (mean, 6 vs. 9 kg) died within 4 months posttransplant. One LDITx recipient developed chronic rejection 3.5 years after the original transplant and died after retransplant. All patients who are alive with functioning grafts are currently on full enteral feeding without need for any intravenous supplementation, except for a recipient of CLDILTx, currently on total parenteral nutrition for late fistula. CONCLUSIONS: The early outcomes of intestinal transplantation from living donors are promising, particularly for candidates in need of CLDLITx. In this subgroup, the elimination of the high mortality on the cadaver waiting list (approximately 30%) represents a substantial advantage.

Living donor kidney transplantation across positive crossmatch: the University of Illinois at Chicago experience.

BACKGROUND: To increase living donation for kidney transplantation, we investigated desensitization of recipients with positive crossmatch against a potential living donor. METHODS: Between June 2001 and March 2007, 57 consecutive sensitized candidates for kidney transplantation, with crossmatch positive potential living donors, were treated with various desensitization protocols. All patients received plasmapheresis every other day with intravenous immune globulin 100 mg/kg starting 1 week before the scheduled transplant. Postoperatively, the recipients continued to receive every other day plasmapheresis with intravenous immune globulin for the initial week. Immunosuppression therapy consisted of induction with thymoglobulin and a combination of tacrolimus, mycophenolate, and corticosteroids. RESULTS: Six patients failed to convert with pretransplant immunomodulation and were not transplanted; 51 underwent live donor kidney transplant. Mean follow-up was 23 months and 36 patients have more than 1-year follow-up. One-year patient and graft survivals were 95% and 93%, respectively. There were 25 episodes of biopsy-proven or clinically presumed rejection in 22 patients in the first year. Of the 17 biopsy-proven episodes, 12 were antibody-mediated rejection and five were acute cellular rejection. Of the patients with antibody-mediated rejection (biopsy proven or empiric), two patients (12%) lost their graft by 1 year. The median modification of diet in renal disease at 6 and 12 months was 55 mL/min (range 9-104 mL/min) and 48 mL/min (range 8-99), respectively. CONCLUSIONS: Despite increased rejection rates, graft and patient survivals indicate that desensitization of positive crossmatch patients is a reasonable alternative for a sensitized patient who could potentially wait 10 or more years for a suitable cadaveric kidney.

Delayed construction of the bilio-digestive anastomosis in right living donor liver transplantation.

We describe a two-step procedure in the transplantation of a right lobe liver graft obtained from a living donor, in which the biliary anastomosis is delayed until the day after the actual implantation of the graft. The purpose of the two-step procedure is to minimize the factors that might contribute to biliary complications in living donor liver transplantation (LDLT). Three patients who received a graft with two hepatic ducts underwent Roux-en-Y hepatico-jejunostomies during a separate procedure the day after the implantation of the graft. Length of intubation, recovery of enteral alimentation, and hospital stay were similar to the patients who underwent one-step transplant. No biliary or infectious complications occurred. Delaying the hepatico-jejunostomy when two ducts are present and a bilio-digestive anastomosis is planned has no negative impact on the postoperative course of the patients but can ameliorate the conditions under which the anastomoses must be performed.

Reported isolated pancreas rejection is associated with poor kidney outcomes in recipients of a simultaneous pancreas kidney transplant.

BACKGROUND: We hypothesized that many reported and presumed isolated pancreas acute rejection episodes in simultaneous pancreas kidney patients may in fact be missed concordant kidney acute rejection episodes. METHODS: To test this hypothesis, we undertook an analysis of the Organ Procurement and Transplant Network database from 1995 to 2006 to assess the impact of reported isolated pancreas rejection on kidney allograft outcomes. The primary outcome of interest was kidney graft status beyond the first posttransplant year. RESULTS: For overall graft survival, we found that when pancreas alone rejection was compared with no rejection there was a significant difference between the curves (log-rank P<0.0001). In addition, this endpoint was also significant for death censored graft survival (log-rank P=0.0036). For both overall and death censored graft survival the multivariate analyses demonstrated an increased risk (adjusted hazards ratio: 2.46, 3.22, respectively) for patients reported to have pancreas alone rejection. CONCLUSIONS: These results indicate that patients with isolated pancreas rejection have worse renal allograft survival than patients reported as having no acute rejection and fare at least as poorly as those with reported kidney graft rejection supporting the concept of concordance of acute rejection in the majority of patients.

Combined living-related segmental liver and bowel transplantation for megacystis-microcolon-intestinal hypoperistalsis syndrome.

BACKGROUND: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is the most severe form of functional intestinal obstruction in the newborn. To date, multivisceral transplantation has been the only accepted treatment modality for these patients, and the results have met with marginal success. We report the first case of a patient affected by MMIHS and cholestatic liver failure treated by a combined living-related liver and intestinal transplant (CLRLITx). CASE REPORT: The patient was a 1-year-old Hispanic girl born with MMIHS and maintained on total parenteral nutrition since birth. Once liver failure developed, she was referred for evaluation for possible CLRLITx. The patient's mother volunteered as the donor. The left lateral segment was used for the liver transplant. The intestinal graft consisted of the terminal 180 cm of the ileum with a single vascular pedicle. Initially, the patient continued to have severe gastroparesis; however, by 8 months posttransplant, stomach function had returned to normal. Currently, at 2 years posttransplant, she is tolerating an oral diet with gastric tube supplementation. Results of absorption studies are within normal, and she has shown catch-up growth. CONCLUSION: A CLRLITx can be a viable alternative for infants diagnosed with MMIHS. This procedure can help avoid the 25% wait-list mortality for children who are in need of a combined transplant.

Living donor liver graft salvage after rupture of hepatic artery pseudoaneurysm.

Hepatic artery pseudoaneurysm (HAP) is an uncommon but life-threatening complication of liver transplantation (LTx). It is often associated with a local infection. Prompt diagnosis and intervention are necessary. We report the first occurrence of such complication in the setting of adult living donor liver transplant. A 48-year-old female with primary sclerosing cholangitis underwent living donor right lobe LTx. Her postoperative course was uneventful. A month later, she developed massive gastrointestinal bleeding, with negative endoscopy and angiography. She rebled 2 weeks later, and an HAP was shown on angiography. On exploration, she was found to have an HAP caused by bile leakage from an accessory bile duct and a dissection of the native artery, likely a result of the angiography. The liver was revascularized using a cadaveric iliac artery conduit between the donor hepatic artery and the aorta, and the hepaticojejunostomy was reconstructed. Biliary complications are the most frequent complications in living donor LTx. A clinically silent bile leak can cause an HAP, resulting in massive gastrointestinal bleeding. Surgical repair and biliary reconstruction can yield an excellent clinical result.

Reconstruction of two bile ducts in a cloaca fashion in living donor liver transplantation.

The presence of two or more hepatic ducts for biliary anastomosis in adult-to-adult right liver transplantation is not uncommon. In the case described here, the graft had two hepatic ducts: one corresponded anatomically to a normal right hepatic duct and the other ran parallel to the proper hepatic duct and drained into its distal to the cystic duct. Because of the small diameter of both duct orifices and the favorable length of the ducts, a cloaca type reconstruction was performed. This allowed the construction of a single and larger orifice for the biliary anastomosis. In case of multiple hepatic ducts of smaller caliber, this technique represents a practical and effective hepatoplasty allowing a single larger anastomosis in the recipient.

Infectious complications associated with the use of rituximab for ABO-incompatible and positive cross-match renal transplant recipients.

Immunosuppressive protocols for ABO-incompatible (ABOI) and positive cross-match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients.

'Prope' tolerance in a noncompliant living related small bowel transplant recipient after severe rejection.

Advances in immunosuppression and surgical technique have greatly improved patient outcomes after intestinal transplantation. However, the procedure remains one of the most challenging among solid organ transplantation as a result of the high rate of acute rejection, sepsis, and posttransplantation lymphoproliferative disorder. Recently, clinical trials to explore tolerance protocols in humans have been initiated, including small bowel transplant recipients, with results not always reproducible. The concept of operational tolerance is more meaningful in the clinical setting when physiological stability of graft function is achieved in the absence of maintenance immunosuppression. We report the intriguing case of a living related small bowel transplant recipient who developed clinical "prope" tolerance to the graft after treatment of severe acute rejection despite continuous noncompliance with immunosuppressive therapy.

Successful rescue of refractory, severe antibody mediated rejection with splenectomy.

Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

Living related segmental bowel transplantation: from experimental to standardized procedure.

INTRODUCTION: Living donor bowel transplantation has recently emerged as a valuable alternative to cadaver bowel transplant. We herein present our single-center experience with this procedure. MATERIALS AND METHODS: From April 1998 to October 2004, 12 living donor intestinal transplants were performed in 11 patients (7 males, 4 females; average age, 26 years). Four of the patients were children under 5 years. A segment of distal ileum 150 to 180 cm long in pediatric recipients and 200 cm long in adult was used. The immunosuppressive protocol consisted of induction with thymoglobulin and maintenance with tacrolimus with or without mycophenolate mofetil and steroids. RESULTS: All donors recovered well and did not experience any early or late complications. The overall 1- and 3-year patient survival was 82% with a graft survival of 75%. In the last 8 patients, transplanted after January 2000, the 1-year patient and graft survival has been 100% and 88%, respectively. The median hospital stay was 36 days (range, 13-290 days). During the first year after transplant only, the patient who received a totally mismatched graft experienced one episode of rejection (8%). All the surviving patients are currently supported by enteral diet without fluid requirements. CONCLUSIONS: Living donor bowel transplantation is a valuable strategy in the treatment of irreversible intestinal failure. The results have improved over the years thanks to increased experience of the team.

Hilar early division of the hepatic duct in living donor right hepatectomy: the probe-and-clamp technique.

The division of the hepatic duct is one of the most challenging passages of the donor hepatectomy. We report our experience with the early division, prior to the liver parenchyma resection, of the hepatic duct and the definition of the biliary anatomy with a probe inserted in the proper hepatic duct. From February 2002 to December 2004, 40 donors (25 male, 15 female; mean age 34, range 20-57) underwent right hepatectomy. The yield was a single duct in 24 donors (60%), two ducts in 12 donors (30%), and three ducts in one donor (2.5%), and three donors had aberrant anatomy yielding two ducts (7.5%). By means of a ductoplasty, a single orifice for the recipient biliary anastomosis was obtained in 77.5% of the cases. Three donors (7.5%) suffered a resection surface bile leak. The technique of hepatic duct probing and early division provides a precise definition of the biliary anatomy and facilitates one of the most challenging passages of the donor hepatectomy. This technique should also contribute to maximizing the preservation of the vascular supply of the hepatic duct and the yield of a single orifice for the recipient anastomosis. At a median follow-up of 21 months (range 10-44), neither short- nor long-term complications had been caused by the small donor choledochotomy.

Routine left robotic-assisted laparoscopic donor nephrectomy is safe and effective regardless of the presence of vascular anomalies.

The classic approach to donor nephrectomy consists of preferential procurement of the kidney without vascular anomalies. We studied the effect of routine procurement of the left kidney regardless the presence of multiple arteries on the outcomes of robotic-assisted laparoscopic living donor nephrectomy (LLDN) with particular reference to the incidence of urological complications. From August 2000 to July 2005, 209 left LLDNs were performed. We analyzed the outcomes of donors and recipients in relation to the presence of multiple vessels versus normal anatomy. We divided the patients into two groups: group A (n = 148) with normal vascular anatomy and group B (n = 61) with vascular anomalies. In the donors, no significant difference in conversion to open surgery rate, blood loss, length of stay, was noted between the two groups; operative time and warm ischemia time were slightly higher in group B. One-year patient survival was 98% in both groups while the 1-year graft survival was 96.6% in group A and 96% in group B. Only one urological complication was noted in the group with normal anatomy (0.7%) versus none in the group with multiple arteries. Left kidney procurement using robotic-assisted laparoscopic technique is safe and effective, even in the presence of vascular anomalies.

Peliosis hepatis in a living related liver transplantation donor candidate.

Peliosis hepatis is a rare benign condition histologically characterized by multiple cystic blood-filled spaces distributed throughout the liver parenchyma. Peliosis hepatis has been associated with malignancies, immunosuppression, infections and medications. We report a case of peliosis hepatis in a candidate for living liver donation, which regressed with restitutio ad integrum, after the noxious stimulus was stopped. We conclude that after diagnosis of peliosis hepatis is established and its cause is removed, simple radiographic imaging is sufficient to document the restitutio ad integrum of the parenchyma, avoiding repeat histological confirmation.

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury.

BACKGROUND: Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients. PATIENTS AND METHODS: Twenty-two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD x2 doses or no TG. No differences in recipients' demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re-vascularization. Post-operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non-function and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non-function and no need for re-transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post-reperfusion) of TG group demonstrated a trend for increased central ballooning. CONCLUSION: The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post-reperfusion are underway.

Increased risk of post-transplant diabetes mellitus despite early steroid discontinuation in Hispanic kidney transplant recipients.

Early steroid discontinuation (ESD) has been associated with a lower incidence of post-transplant diabetes mellitus (PTDM). We retrospectively reviewed the incidence of PTDM in relation to racial groups in kidney transplant recipients treated with ESD. Between January 2002 and September 2003, 125 consecutive primary adult kidney transplants were performed. Group A (n = 91) had steroids discontinued on postoperative day 6 and maintenance immunosuppression of Tacrolimus and mycophenolate mofetil. Group B (n = 34), received the same immunosuppression but was maintained on steroids indefinitely. Induction consisted of thymoglobulin in African-Americans; all others received Simulect. At 1 yr, patient/graft survival, serum creatinine and rate of acute rejection were similar in both groups. The incidence of PTDM was significantly lower in group A (7%) compared with group B (26%, p = 0.0209). The incidence of PTDM in group A was limited to Hispanic patients with a family history of diabetes mellitus. African-Americans and Caucasians in group A did not experience PTDM (p = 0.005 compared with African-American in group B). Our steroid free protocol nearly eliminated the incidence of PTDM in African-Americans and Caucasians, but was still associated with significant rate of PTDM in Hispanic recipients. Alternative immunosuppression may benefit this population.

Early discontinuation of steroids is safe and effective in pediatric kidney transplant recipients.

In pediatric kidney transplantation, steroid induced growth retardation and cushingoid features are of particular concern. In children, gradual steroid withdrawal late after kidney transplantation increases the risk of rejection. In this pilot study, we investigated the outcome of pediatric renal transplantation with an early steroid withdrawal protocol. This is a retrospective case-control study of pediatric renal transplants with age-matched historical control. Groups were comparable in terms of HLA matching, donor type and graft ischemia time. In the steroid withdrawal group (SWG, n = 13), induction therapy included mycophenolate mofetil (MMF) and a 5-day course of steroids with Thymoglobulin in 11 and basiliximab in two other patients. In the steroid group (SG, n = 13), in addition to steroids, four patients were given basiliximab, eight were given Thymoglobulin, and one OKT3. Maintenance therapy included tacrolimus (SWG n = 11, SG n = 3) or cyclosporine (SWG n = 2, SG n = 10). Azathioprine was given to all the patients in the SG, except the last two patients of this series who were prescribed MMF. MMF was given to all in the SWG. Patient and graft survival rates were 100% in both groups. In the SWG, no acute rejection episode was detected. In the steroid group, three patients (25%) presented with an acute rejection episode. All but one patient in either group showed immediate graft function. Patients in the steroid-withdrawal group exhibited a significantly higher creatinine clearance at 6 and 12 months post-transplant (95.8 +/- 23.3 vs. 71.3 +/- 21.9, p = 0.03; and 91.3 +/- 21.6 vs. 69.6 +/- 28.6, p = 0.04). In the SWG delta BMI was significantly lower and delta height Z score was significantly higher, and we observed significantly less hyperlipidemia, body disfigurement, and need for anti-hypertensive medication. Early steroid withdrawal in pediatric renal transplant recipients is efficacious and safe and does not increase risk of rejection, preserving optimal growth and renal function, and reducing cardiovascular risk factors.