Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial.

A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.

Normal thiopurine methyltransferase levels do not eliminate 6-mercaptopurine or azathioprine toxicity in children with inflammatory bowel disease.

6-mercaptopurine (6-MP) and azathioprine (AZA) are used to treat inflammatory bowel disease (IBD). Side effects include infection, leukopenia, hepatitis, and pancreatitis. The level of thiopurine methyltransferase (TPMT), which metabolizes 6-MP to 6-methylmercaptopurine, may reflect the risk of side effects. We sought to evaluate the relationship between the side effects of these medications and the TPMT level of pediatric patients with IBD. The medical records of our patients who were diagnosed with IBD and who received 6-MP or AZA were reviewed for measured TPMT levels. All red blood cell (RBC) TPMT levels were determined at the Mayo Medical Laboratories, Rochester, MN. The occurrence of leukopenia, elevated aminotransferases, and pancreatitis was evaluated. Twenty-two patients, mean age 13.7 years, received 6-MP or AZA and had TPMT levels measured. The TPMT levels ranged 10.7-27.5 U/mL RBC with a mean of 17.2 +/- 3.2 U/mL RBC. Two children had levels below the accepted norm of 13.8 U/mL RBC. One of these patients (50%) developed both elevation of aminotransferases and leukopenia. Of all, 20 children had normal levels, 3 (15.0%) exhibited side effects: hepatitis (n = 2) and leukopenia (n = 1). We conclude that side effects of 6-MP or AZA occur despite normal TPMT levels.

Azathioprine and 6-mercaptopurine for the treatment of perianal Crohn's disease in children.

Numerous adult studies show a 30-65% response rate to azathioprine (AZA) or 6-mercaptopurine (6-MP) for significant perianal Crohn's disease. The aim of this study was to evaluate whether these drugs healed pediatric perianal Crohn's disease. Records of pediatric Crohn's patients were retrospectively reviewed for significant perianal disease treated with AZA or 6-MP for > or =6 months. The patient's perianal disease was reviewed and evaluated for fistulas, drainage, induration, and tenderness. In addition, the patients were given a score using the Irvine Perianal Disease Activity Index (PDAI). Patients were retrospectively scored upon initiation of treatment and after six months of therapy. Possible scores ranged from 0-20. Twenty patients met the study criteria. Five patients were considered treatment failures. One patient required a colostomy after 1.5 months of therapy, one developed pancreatitis, and three were noncompliant with therapy. Of the remaining 15 patients who were treated for > or =6 months, 67% had an improvement in drainage, 73% in tenderness, 60% in induration, and 40% in fistula closure. The mean Irvine PDAI was 7.67 +/- 2.19 initially and 4.40 +/- 1.72 after six months of therapy. The improvement was statistically significant (p < 0.001). AZA and 6-MP are effective treatments for healing significant perianal Crohn's disease in pediatrics.

Supraceliac aortic pseudoaneurysms after liver transplantation in infants.

BACKGROUND: Reconstruction of the hepatic artery in infants undergoing liver transplantation presents challenging vascular situations. Microvascular techniques ensure arterial blood flow via small caliber vessels but are insufficient when inflow is poor. In these situations, the use of allogeneic grafts to the supraceliac aorta have been advocated. The development of a pseudoaneurysm at the supraceliac aortic suture line requires urgent repair and restoration of arterial flow to the graft. METHODS: Our study was based on case reports and review of the literature. RESULTS: Definitive diagnosis and successful repair of supraceliac pseudoaneurysm was accomplished in two infants after transplantation. CONCLUSION: We advocate a thoracoabdominal retroperitoneal approach, which provides safe control of the aorta and primary repair or patching of the diseased aortic segment, and also provides access for hepatic revascularization via placement of an infrarenal graft. Thrombosis of the artery and subsequent liver necrosis are indications for retransplantation.

Liver transplantation at the University of Pennsylvania and the Children's Hospital of Philadelphia.

The liver transplant program at the University of Pennsylvania and the Children's Hospital of Philadelphia experienced healthy growth in its clinical activity in the past 5 years. Patterns of referral and patient evaluation were established, care of patients while waiting on the list or being followed after transplantation was streamlined. We are now achieving excellent outcomes while transplanting relatively sicker patients. Innovative surgical procedures are implemented resulting in more efficient utilization of cadaveric and living-donor liver grafts. The protocols that are used for patient care are more standard, yet flexible and accommodate recent advancement in transplantation immunobiology. This progress of the clinical program was enhanced by careful preservation of the academic mission of the institution, which encourages the liver transplant faculty to be involved in NIH-supported clinical and basic science research.

Single toxin detection is inadequate to diagnose Clostridium difficile diarrhea in pediatric patients.

BACKGROUND & AIMS: Clostridium difficile is an important cause of symptomatic diarrhea in pediatric patients. The bacterium produces two toxins, although many laboratories assay for only one. We questioned this diagnostic approach when patients had positive results for C. difficile at our institution, but initially had tested negative at outside laboratories. METHODS: We retrospectively analyzed relative frequencies of C. difficile toxin A alone, toxin B alone, and toxins A and B from pediatric patients with diarrhea. Results were stratified according to toxin detection and patient age. RESULTS: Of 1061 specimens, 276 (26.8%) were positive for C. difficile toxin(s). Fifty-one (18.5%) were positive for toxin A alone, 133 (48.2%) for toxin B alone, and 92 (33.3%) for both toxins. Assaying for toxin B identified C. difficile infection more frequently than did assaying for toxin A (P < 0.0001). The frequency of toxin B detection was significantly higher for older children but not for infants. CONCLUSIONS: Testing for C. difficile toxin A or toxin B alone will result in more frequent misdiagnosis than testing for both toxins. This practice may lead to inappropriate further invasive investigations in children, although this finding may not be applicable to adults.

Breakdown of gastric staple line as a complication of the uncut Collis-Nissen fundoplication in children.

Uncut Collis-Nissen fundoplication for complicated gastroesophageal reflux was performed in 102 children (46 girls; age 5.6 +/- 4.2 years). Five patients developed intractable emesis postoperatively (average 11 +/- 5 months after surgery) and were found to have two independent luminal openings at the gastroesophageal junction seen on upper endoscopy but not demonstrable on upper GI. The defect was presumed to occur from breakdown of the original staple line on the lesser gastric curve. The condition was successfully repaired in all patients by including a new staple line and rewrapping of the stomach. Practitioners should be aware of this previously unreported complication post uncut Collis-Nissen fundoplication and that this condition may not be excluded by a normal upper GI study.